First Impact Factor released in June 2010 and now listed in MEDLINE!

SYMPOSIA

Symposium Session 1 Monday November 17, 1:00–2:25 p.m., Concord A The NIMH RAISE ETP (Early Treatment Program): initial results Chair: John Kane, The Zucker Hillside Hospital; speakers: Nina Schooler, Delbert Robinson, Jean Addington, John M Kane The goal of the NIMH RAISE-ETP (Early Treatment Program) is to assess whether state-of-the-art pharmacologic and psychosocial treatments delivered by a trained team (NAVIGATE) can improve the functional outcome and quality of life for first episode psychosis (FEP) patients. The study is being conducted in non-academic USA treatment settings, using primarily extant reimbursement. We developed NAVIGATE and a training program based on literature review and expert consultation. RAISE-ETP compares it to “usual care” on quality of life, remission, recovery and cost effectiveness. Patients 15–40 years old with a first episode of schizophrenia spectrum disorder and no more than 6 months antipsychotic medications were eligible. Subjects are followed for a minimum of 2 years, with major assessments conducted by blinded, centralized raters using live, two-way video. We selected 34 clinical sites in 21 states and utilized cluster randomization to assign 17 to NAVIGATE and 17 to usual care. Enrollment began in July 2010 and ended in July 2012 with 404 subjects. Nina Schooler will present the study design, describe site selection, the randomization process and assessments. Delbert Robinson will present the pharmacologic treatment model, its implementation with the assistance of a computerized decision support system and the nature of the pharmacotherapy received by both groups. Jean Addington will present the design and implementation of the psychosocial treatment model. John Kane will present the overall results of the experimental intervention in comparison to usual community care after 2 years of treatment and follow-up.

Pharmacological treatment in the RAISE-ETP Study Delbert Robinson1,2,3 1

The Feinstein Institute for Medical Research, Center for Psychiatric Neuroscience, Manhasset, New York, USA, 2Hofstra North Shore-LIJ School of Medicine, Departments of Psychiatry and of Molecular Medicine, Hempstead, New York, USA, 3The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York, USA Introduction: RAISE-ETP compares NAVIGATE, an integrated treatment program, with usual care at community clinical facilities. Our goal for NAVIGATE medication treatment was that it (1) incorporated research findings about the specialized medication approaches needed for people with early phase schizophrenia-spectrum disorders, (2) be tailored to individual needs and preferences and (3) could be implemented by community prescribers without prior specialized early phase training or experience. Methods: We convened a panel of experts and reviewed the early phase medication treatment literature. Study medication treatments had to be limited to standard agents given the study mandate to assess outcomes in typical community facilities. The study focus upon shared decision making and the fact that no antipsychotic has been demonstrated to be more efficacious than others for initial first episode treatment led to the decision to have groups of recommended medications for each treatment stage instead of a single medication algorithm. Medication treatment used COMPASS, a NAVIGATE-developed computer clinical decision making tool accessed via a secure website. COMPASS facilitated subject–prescriber communication through direct subject input of information about symptoms, side effects, treatment preferences and other issues into the system. These data then guided prescribers in their sessions with subjects. COMPASS employed a measurement-based care model in order to provide guidance about evidence-based medication strategies that informed subject-prescriber decision making about medication treatment. Results: Subjects and prescribers completed more than 3000 COMPASS visits, demonstrating the feasibility of COMPASS treatment. Further analyses of the effects of COMPASS treatment will be presented at the meeting.

Psychosocial treatment in the RAISE-ETP study Jean Addington University of Calgary, Calgary, Alberta, Canada

RAISE-ETP study design, site selection and implementation model Nina Schooler SUNY Downstate Medical Center, Brooklyn, New York, USA The RAISE-ETP study design was driven by the goal of evaluating an integrated treatment for first episode psychosis (NAVIGATE) in non-academic, community sites in the USA. This required the development and training of a treatment team at each site. We selected 34 sites, located in 21 states, and randomized the sites (clusters), rather than individuals, to either implement NAVIGATE or to provide customary Community Care for subjects in the study. Cluster randomization insured that clinicians at Community Care sites were not exposed to NAVIGATE in order to avoid spillover/contamination effects. Conduct of the study in non-academic settings and the inability to blind psychosocial treatments drove our assessment strategy. We utilized a remote, central rating team of highly trained clinical raters provided by MedAvante blinded both to the overall study design and to the treatment of subjects. They conducted major clinical assessments via live, two-way video at study entry and every 6 months. At study entry and after 1 year, they completed full diagnostic assessments to confirm eligibility. Other assessments (e.g. services received, vital signs, laboratory tests and cognitive testing) were completed on site. Subjects were between 15 and 40 years old, had received less than 6 months of anti-psychotic medication and were experiencing a first episode of psychosis. Study enrollment was completed in July 2012 with 223 subjects receiving NAVIGATE and 181 Community Care. Data from 2 years of treatment and follow up will be available in July of 2014. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Introduction: RAISE-ETP compares NAVIGATE, an integrated treatment program, with usual care at community clinical facilities. The goal for the psychosocial treatment component of NAVIGATE was that it could be individually tailored to the needs and preferences of individuals experiencing a first episode of psychosis (FEP) and secondly, it could be implemented in routine, non-academic US community mental health centers. Methods: The psychosocial program consists of three psychosocial interventions that are all manually based. (i) The Family Education Program focuses on engagement of families and facilitating and promoting prolonged recovery. (ii) The Individual Resiliency Training (IRT) is an individual modular treatment that focuses on helping clients achieve their goals by developing their own resiliency and learning skills to manage their illness and improve functioning. IRT consists of standard psychoeducational modules plus individualized modules that address coping with distress and persistent symptoms, substance abuse, improving social and leisure functioning, and addressing health issues. (iii) The Supported Employment and Education (SEE) is based on principles of IPS supported employment broadened to address education and adapted for individuals with a recent FEP. SEE services include assessment, job search or school enrollment and follow-along supports. The psychosocial treatment team, which works collaboratively, endorsing a shared-decision making approach, consists of a team-leader who is typically the family worker, one or two IRT therapists and a SEE specialist. Results: Approximately 200 participants have completed much of psychosocial treatment. Results of the effects of the psychosocial treatment will be presented at the meeting.

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9th International Conference on Early Psychosis The RAISE ETP study: initial results John M Kane1,2

Abnormal resting cerebral blood flow (rCBF) reflects change in functioning in subjects at ultra high risk for psychosis

The Zucker Hillside Hospital, Glen Oaks, New York, USA, 2Hofstra North Shore-LIJ School of Medicine, Hempstead, New York, USA

Paul Allen

The RAISE-ETP program was designed to develop and evaluate an integrated treatment for first episode psychosis (NAVIGATE) in “real world,” non-academic, community treatment sites in the USA We selected 34 clinics, located in 21 states, and randomized the sites (clusters), rather than individuals, to either implement NAVIGATE or to provide customary Community Care for subjects in the study. Cluster randomization insured that clinicians at Community Care sites were not exposed to NAVIGATE in order to avoid spillover/contamination effects. Diagnostic interviews and major assessments were conducted by trained remote, centralized personnel utilizing live, two-way video. This allowed them to remind blind to study design and treatment assignment. Study enrollment was completed in July 2012 with 223 subjects receiving NAVIGATE and 181 Community Care. The final RAISE ETP study sample consisted of 404 subjects. Mean age is 23, 73% are male, 54% Caucasian, 37% African American. Eightyeight (17%) were recruited from community outreach activities for the study and the remaining 335 (83%) of subjects came from the usual referral sources for the sites (e.g. a local inpatient unit). Approximately half of subjects met DSM-IV criteria for schizophrenia at study entry with the next most common diagnoses being schizophreniform disorder and schizoaffective disorder and 83% had had severe enough symptoms to warrant psychiatric inpatient hospitalization. Data from 2 years of treatment and follow up will be available in July of 2014 and initial results will be presented.

Continuous arterial spin labeling (cASL) is an MR perfusion technique suitable for translational applications as the associated scanning protocols are relatively simple and short. The aim of the study was to investigate whether resting cerebral blood flow (rCBF), measured with cASL, is altered in individuals at ultra high risk (UHR) of psychosis and whether rCBF is sensitive to longitudinal clinical change in an UHR group. cASL imaging was used to measure rCBF in 52 individuals at UHR of psychosis and 30 healthy control participants. Subjects were rescanned a mean 16 months later, and symptoms and global functioning were re-assessed. Symptoms were assessed using the Comprehensive Assessment of At Risk Mental States (CAARMS) and functioning was measured using the Global Assessment of Functioning (GAF). At baseline UHR subjects showed significantly elevated rCBF in prefrontal cortex (PFC), striatum, hippocampus and cingulate cortex. Between baseline and follow-up scans, rCBF remained stable in the controls group but there was a significant reduction in rCBF within the UHR group, particularly within PFC. Within PFC regions, the change in rCBF was associated with improved function over time. In the UHR group, there was also an association between the longitudinal reduction in hippocampal rCBF and psychotic symptoms. This is the first study using cASL to measure rCBF in a psychosis UHR cohort. In the UHR group, baseline hyperperfusion normalized over time. The longitudinal change in rCBF was associated with clinical and functional improvement in the UHR cohort.

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Symposium Session 2 Monday November 17, 1:00–2:25 p.m., Concord B Future directions in neuroimaging studies of early psychosis: are we ready to translate research evidence into clinical utility? Chair: Kiyoto Kasai, The University of Tokyo; speakers: Paul Allen, Shinsuke Koike, Naohiro Okada, Andrea Mechelli Longitudinal clinical investigations of early psychosis have revealed not only progressive neuroanatomical and neurofunctional changes but also developmental alternations consistent with the gene–environment interaction model. However, these studies have had minimal impact on the identification and management of early psychosis in everyday clinical practice. The past few years have seen a shift from basic research on the disorder toward investigations with a more explicit translational focus. In this context, the development of standardized protocols for data acquisition and the introduction of analytical techniques that allow inferences to be drawn at individual level, have provided new opportunities to bridge the gap between basic research and clinical practice. The present symposium will consider the potential of so-called third-generation neuroimaging for translating research evidence into clinical utility. The focus will be on possible ways in which neuroimaging could be used to improve clinical care in early psychosis; the existing theoretical and practical challenges to successful translational implementation; and how these challenges could be overcome in the near future. Specific topics will include the neuronal correlates of vulnerability in adolescence and adulthood, continuous arterial spin labeling, near-infrared spectroscopy, machine learning methods, multi-modal neuroimaging, and epidemiological neuroimaging.

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Institute of Psychiatry, King’s College London, London, UK

Reduced rostral prefrontal cortex activity is associated with poor functional outcome in ultra-high risk and first-episode psychosis Shinsuke Koike, Yoshihiro Satomura, Yukika Nishimura, Ryu Takizawa, Kiyoto Kasai The University of Tokyo, Tokyo, Japan Longitudinal clinical investigations and biological measurements for psychosis have enabled us to clarify not only progressive brain volumetric and functional changes but also the alternations of developmental pathways based on gene–environment interaction model. However, these studies have little contribution to clinical decisions on differential diagnosis and therapeutic choices. Near-infrared spectroscopy (NIRS) is a relatively small instrument with little noise that can easily and noninvasively measure hemoglobin changes over the surface of the cortex. NIRS instruments are easily moved including clinics and care units, and therefore, a candidate for clinical use in psychiatry. Our previous NIRS studies demonstrated that patients with stable chronic schizophrenia showed impaired activity and characteristic wave form patterns over the prefrontal cortical regions during a letter version of verbal fluency task, and that the activity in the rostral part of the prefrontal cortex was associated with the patients’ present symptoms. A cross-sectional study that focused on four different clinical stages of psychosis (controls, ultra-high risk, first-episode psychosis, and chronic schizophrenia) indicated varying activity patterns for different prefrontal cortical subregions. In this session, we will show the results of longitudinal investigation to elucidate whether (1) NIRS signals in the PFC predict the future and/or present clinical outcome and (2) the longitudinal trajectory of NIRS signal changes from the first-episode to chronic stages. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Investigating developmental trajectory of self-regulation and vulnerability to psychosis by neuroimaging: subsample of Tokyo Teen Cohort study Naohiro Okada, Noriaki Yahata, Kiyoto Kasai The University of Tokyo, Tokyo, Japan Tokyo Teen Cohort (TTC) study is a large-scale general population-based survey to elucidate puberty development during adolescence, especially the acquisition process of self-regulation and willingness to challenge, through focusing on interaction between bio, psycho, and social factors. Participants include 5,000 10-year-old children and their carers living in Tokyo Metropolitan area. Information about characteristics of daily life, family form, physical and mental health, and puberty onset as well as about self-regulation and psychological well-being is acquired from participants. Furthermore, we conduct a biological subsample study following as an extension of TTC study. In the subsample study, we intend to collect hormone and DNA derived from saliva and brain structural and functional MRI images from 200 children who took part in TTC study, to explore what facilitates or obstructs successful development of mental health during adolescence at the hormonal, genomic, and neural level. Little is known about the pathology involved in the preclinical stage of early psychosis. In adolescence young people acquire various advanced mental functions such as self-regulation and it is speculated that disturbance of these functions may enhance vulnerability to the onset of early psychosis. In this session, we will illustrate the result of our MRI study on neural substrates of self-regulation in adolescence, which might afford better insight into pathology of vulnerability to psychosis or potential pathological changes preceding the onset of psychosis. Then we will discuss the validity of our current results and the future directions.

Symposium Session 3 Monday November 17, 1:00–2:25 p.m., Concord C Early intervention in psychosis: Asian context Chair: Matcheri Keshavan, Harvard Medical School, Beth Israel Deaconess Medical Center; co-chair: Larry Seidman, Harvard Medical School, Beth Israel Deaconess Medical Center; speakers: Masafumi Mizuno, TianHong Zhang, Kristen A Woodberry, Sherry Chan In recent years, there has been an increasing interest in developing psychosis early detection (ED) and intervention (EI) programs throughout Asia. Early intervention in psychotic illnesses can potentially prevent relapse and functional disability, and may favorably modify the course of the disease; ED and EI in the prodromal phase can potentially prevent conversion to psychosis, and reduce disability. While the principles and practices of ED/EI in psychoses are similar across societies, the specific challenges, resources and strategies to develop programs are likely to vary considerably. There is clearly a need to review the cross-cultural aspects of ED/EI in Asia and in North America. With this goal in mind, the proposed symposium seeks to bring together experts in EI from the Asian countries of Japan (Masafumi Mizuno) and China, from Hong Kong (Eric Chen), and Shanghai (TianHong Zhang). Kristen Woodberry will review her experience of ED/EI programs in two US settings (PREP/CEDAR in Boston and PIER in Maine). The key questions to be addressed by the presenters are (A) How do patients in the early phases of the psychosis and prodrome present in your setting? (B) What are the challenges you face in your setting for early detection and intervention? and (C) What are the strategies you have found useful in developing ED and EI services in your setting? Larry Seidman will discuss the salient points, outline gaps in the field and potential steps for the future.

Implementing early intervention in Japan: its challenges and difficulties Masafumi Mizuno Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan

Current state-of-the-art in the development of neuroimaging markers in early psychosis Andrea Mechelli Institute of Psychiatry, King’s College London, UK Despite the publication of hundreds of neuroimaging articles on the neuroanatomical and neurofunctional correlates of psychosis, the findings have not resulted in any significant changes in everyday clinical practice. In my presentation, I will provide a brief overview of the current state-ofthe-art regarding the development of diagnostic and prognostic neuroimaging markers in psychosis. As part of this overview, I will discuss the main theoretical and practical challenges that need to be overcome in order to be able to translate current neuroimaging research evidence into clinical practice. I will then discuss the use of machine learning methods as a possible way of overcoming some of these challenges. Machine learning methods allow inferences at single-subject level and, therefore, have the potential of informing the diagnostic and prognostic assessment of individual patients. I will show a number of recent applications of machine learning methods in the context of early psychosis, and will consider how this approach could be used to develop stratified interventions in everyday clinical practice. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

For many years, the reliance on hospital-based psychiatry has been a barrier for the development of community-based psychiatry in Japan and increased stigma against mental illness and people suffering from psychiatric disorders. Even in this adverse situation, some innovative hospitals have attempted to make the transition to community-based psychiatry through their own endeavors. Simultaneously with these gradual changes, the key concept of early intervention and detection in the critical period for treatment is spreading among psychiatric professionals and some innovative centers have started their activities mainly from university centers. Therefore, special approaches for early psychosis cases could be administered mainly in university centers for the referred cases from general practitioners or psychiatrists in private clinics and the numbers of cases are very limited. Poor mental health literacy due to lack of education in schools increases the difficulties of the earlier phase cases to come directly to the centers. The researchers and clinicians in the centers need to publicly announce or inform the importance of early intervention for increasing and implementing EI. All the communicating tools including media and websites should be utilized for sending the information on the activities and possibilities of EI. Community meetings of medical professionals and school teachers, parents, and all related persons must be important for developing the referral network for early detection. These efforts are limited for those regions that currently have early intervention centers in Japan. The models for EI in the community should be flexible and characteristic for each area.

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9th International Conference on Early Psychosis Detection and prediction of psychosis in a clinical high-risk Chinese sample: turning challenges into opportunities in an eastern social context TianHong Zhang,1 Huijun Li,2 Kristen A. Woodberry,3 Larry J. Seidman,3 Jijun Wang1 1 Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China, 2Florida A & M University, Tallahassee, Florida, USA, 3Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

Introduction: Chinese psychiatrists have gradually focused on those who are deemed to be at “clinical high-risk” (CHR) for psychosis; however, it is unknown whether those CHR individuals from a different cultural background than previously studied would convert to psychosis. In other words, does cultural context influence the likelihood of conversion? Method: 2101 consecutive new subjects ages 15–45 were recruited at their first visit to the Shanghai Mental Health Center (SMHC). A total of 117 subjects were considered to be CHR based on the Structured Interview for Prodromal Syndromes (SIPS). Those subjects were followed for at least 2 years. We will discuss their outcomes and also present a Chinese CHR female case to understand the more detailed processes by which an individual deals with prodromal psychosis in her everyday live. Information regarding her symptoms, life stressors and social activities will be discussed. Results: The frequency estimate of CHR syndromes in the total sample was 4.2%. Out of 117 CHR participants, 86 (73.5%) completed the followup. Twenty-five (29.1%) transitioned to a psychotic disorder. The conversion subgroup had a lower level of functioning, a higher total score of SIPS positive symptoms, and a longer duration of untreated prodromal symptoms at baseline.

10-year outcome study of an early intervention programme for psychosis in Hong Kong compared with standard care service Sherry Chan, Eric Chen University of Hong Kong, Hong Kong Despite convincing evidence on the short-term benefits of early intervention (EI) service for psychosis, long-term outcome studies are limited with inconsistent results. Current study has examined the 10-year outcomes of patients with first-episode psychosis who received 2-year EI service (EASY) compared with those who received standard care (SC) in Hong Kong using historical control design. Consecutive patients who received EI service in the whole territory between 1 July 2001 and 30 June 2002, and with diagnosis of schizophrenia-spectrum diagnosis, were identified and matched with patients who received SC first presented to the public psychiatric service from 1 July 2000 to 30 June 2001. 148 matched pairs of patients were identified. Cross-sectional information on symptomatology and functioning was obtained through semi-structured interview; longitudinal information on admission, functioning, suicidal attempts, mortality and relapse over 10 years was obtained from clinical database. 70.3% (N = 104) of SC and 74.3% (N = 110) of EI patients were successfully interviewed. Results suggested that EI patients had fewer number (OR = 1.56, χ2 = 15.64, p < 0.0001) and shorter duration of hospitalization (OR = 1.29, χ2 = 4.06, p = 0.04), longer employment period (OR = −0.28, χ2 = 14.64, p < 0.0001), less suicidal attempts (χ2 = 11.47, df = 1, p = 0.001), better survival over 10 years. At 10 years, EI patients had less depressive symptoms (F(1.201) = 5.78, p = 0.02) though no difference was found on psychotic symptoms, symptomatic remission and functional recovery between groups. The short-term benefits of EI service on number of hospitalization and employment sustained after termination of the service, but the differences narrowed down. This suggested the need of evaluating the optimal duration of EI service.

Conclusions: This Chinese CHR sample had a similar transition rate in the 2-year follow-up compared with findings from other cultural groups. Effective treatment strategies may include teaching individuals to gain insight related to their symptoms and group or family therapy that provides a context in which individuals can discuss their psychotic symptoms.

Symposium Session 4 Monday November 17, 2:30–3:55 p.m., Concord A Early detection and intervention in two US centers and a US– China collaboration Kristen A Woodberry Beth Israel Deaconess Medical Center, Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA In the United States, early detection (ED) and intervention (EI) have developed in the context of a largely private insurance system. Mental health services are reimbursed for diagnosable disorders only and to a more limited extent than physical disorders. Mental health prevention and EI services are not covered. ED and EI services and centers were initiated, beginning in the mid-1990s, with a mixture of private and federal grant funding and insurance-reimbursable care within innovative clinics and academic centers. Help-seeking adolescents and young adults at clinical high risk (CHR) were identified within existing clinic populations and recruited through extensive education and outreach to primary care, secondary and post-secondary schools, mental health clinicians, and community partners. The promise of free and/or specialized assessment and treatment was essential to securing community referrals. Thoughtful publicity campaigns and targeted outreach were necessary to counter public concern about unnecessary stigmatizing of youth who might never develop psychosis. Challenges include sustained funding for clinical ED and EI services (1) prior to diagnosable mental illness, and (2) that have the flexibility to engage non-help-seeking youth at home or in the community. Private–public partnerships that can support stable infrastructure and specialized training, outreach and clinical consultation for community providers have been essential to developing and maintaining ED and EI services. Examples highlighting challenges and strategies will be provided from the PIER, CEDAR, and PREP programs in New England, the North American Prodrome Longitudinal Study (NAPLS), and a collaborative project with Shanghai Mental Health Center.

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The application of clinical staging models and ‘at risk’ criteria to mood disorders Chair: Andreas Bechdolf, Academic Hospital of Charite Medicine Berlin, and University of Cologne; co-chair: Jan Scott, University of Newcastle, UK; speakers: Judith Verduijn, Ian Hickie, Andreas Bechdolf, Jan Scott This symposium brings together international researchers from the Netherlands, Germany, UK and Australia who share an interest in the identification of individuals at high risk of developing severe or recurrent mood disorders and the utility of clinical staging models in mood disorders. The studies that will be presented were undertaken in community, youth mental health, early intervention in psychosis and mood disorder service settings. The symposium examines the changing approach to this research and the new methodologies that may help predict transition from ‘at risk’ states to stage 2 and/or later stages of mood disorders. The symposium will be chaired by Andreas Bechdolf (Germany), with Jan Scott as a vice chair. The symposium aims to provide an overview of the translation of clinical staging models from psychosis to mood disorders, to explain the importance of this approach in understanding disease progression and to look at putative biosignatures for different stages. Bechdolf and Scott will give presentations on the reliability and validity of symptom clusters that predict likelihood that ‘at risk’ individuals will make an early transition to bipolar disorder. Verduijn will report on a community study that examined the validity of current staging models for depressive disorders. Lastly, Hickie will examine staging in depression and bipolar disorders including a discussion of genetic and neuroimaging markers of differential trajectories. Given the prominence of the issue of clinical staging models and the need to better understand differential transitions and/or progression through each clinical stage, we believe the symposium would have wide appeal. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Clinical staging of major depressive disorder: an empirical exploration

The predictive validity of bipolar at-risk (prodromal) criteria in help seeking adolescents and young adults: a prospective study

Judith Verduijn, Yuri Milaneschi, Aartjan Beekman

Andreas Bechdolf,1 Ashwin Rasheeth,2,3 Sue Cotton2,3

Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands

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We examined the construct and predictive validity of a clinical staging model for major depression that distinguishes eight consecutive stages (0, 1A, 1B, 2, 3A, 3B, 3C, 4) based on severity and duration of symptoms, and number of episodes. At baseline 2334 Netherlands Study of Depression and Anxiety participants were assigned to the eight stages of the model, of them 2012 were followed-up after 2 years. For construct validity, differences between stages in clinical characteristics (e.g. severity, age of onset, co-morbid anxiety) were studied. Predictive validity was measured by the extent to which baseline stages predicted 2-year follow-up outcomes (e.g. MDD presence). Most clinical characteristics and follow-up outcomes showed a significant linear trend across stages with later stages having worse outcomes than early stages, confirming validity of the model. Both construct and predictive validity analyses suggest that the model performs best in the early (mostly pre-clinical) stages (0, 1A, 1B, 2). However, in the later (clinical) stages (2, 3A, 3B, 3C, 4), validity analyses showed no differences between each consecutive stage, but only between stages with longlasting symptoms (3A, 4) compared to stages differing in number of episodes (2, 3B, 3C). This study showed reasonable validity for a depression staging model that based its stages purely on clinical characteristics. Results suggest that, contrary to the number of episodes, duration of exposure to the depressed state best characterizes later stages.

Department of Psychiatry, Psychotherapy and Psychosomatics, Vivantes Klinikum am Urban, Berlin, Academic Hospital of Charite Medicine Berlin, Germany, 2Orygen Youth Health Research Centre, Parkville, Australia, 3 Centre for Youth Mental Health, University of Melbourne, Parkville, Australia There are no established tools to identify individuals at risk for developing bipolar disorder. We developed a set of risk criteria for bipolar affective disorder (bipolar at-risk – BAR) and tested their predictive validity in a 12-month prospective study that was conducted at Orygen Youth Health Clinical Program (OYH). At intake, BAR screen-positive individuals and a matched group of individuals who did not meet BAR criteria were observed over a period of 12 months. The BAR criteria include general criteria such as being in the peak age range of the onset of the disorder, as well as subthreshold mania, depression plus cyclothymic features and depression plus genetic risk. Conversion to first episode mania/hypomania was defined by the presence of DSM-IV manic symptoms for more than 4 days in line with DSM-IV definition of hypomania/mania. Of 559 help-seeking patients, about 10% met BAR criteria. 35 participants were included in the BAR group and 35 matched participants were selected to be in the control group. During the follow-up, five BAR patients out of 35 (14.3%) converted to first episode hypomania/mania as opposed to none in the non-BAR group (χ2(1) = 5.38, p = .020). Four out of these five converters had a DSM IV diagnosis of BD I or II. These findings support the possibility of identification of persons prior to the onset of mania/hypomania. The proposed criteria need further evaluation in bigger, prospective studies with longer follow-up periods.

Screening strategies to identify individuals at high risk of developing a bipolar disorder Jan Scott

Clinical staging models and risk of bipolar disorder

Institute of Neuroscience, Newcastle University, UK

Ian Hickie

Bechdolf and colleagues recently developed a BD ‘at-risk’ (BAR) assessment tool for use with help-seeking individuals. The BAR assessment incorporates general criteria and specific criteria, such as cyclothymia, sub-threshold mania, depression and genetic risk. Utilisation of these criteria in early intervention services has produced promising findings. However, a specific challenge for such assessment tools is not just their ability to identify BD at risk cases from young people with heterogeneous problems and disorders, but also to discriminate between which individuals from within populations with early onset depression are at risk of imminent ‘conversion’ to BD as compared to recurrent unipolar disorder (UP). This is of great importance clinically and as such is an important challenge to the utility of the BAR criteria. The present study aims to address these issues and we report the (a) validity of the BAR criteria in differentiating early onset BD from UP, in cases matched for gender and year of birth, all of whom had previously participated in systematic screening assessments; (b) clinical utility of the BAR criteria, and four additionally selected risk factors for either finding cases or screening out non-cases (including activation/fatigue); (c) ‘number needed to screen’ (NNS) using systematic assessments and predict the NNS if case finding strategies using ‘at risk’ criteria were to be translated in routine, general psychiatry settings; (d) results of ‘alternative’ approaches such as using established screening questionnaire such as the HCL and MDQ. The BAR criteria, plus the atypical depression symptoms, performed better than the established screening tools. It is also noted that the later have also predominantly been tested in older rather than younger adults.

Brain & Mind Research Institute, University of Sydney, Sydney, Australia A major challenge for early intervention psychiatry is to identify those persons who are at increased risk of developing recurrent unipolar or bipolar mood disorders, assuming that such identification will lead to interventions that reduce poor long-term outcomes This paper will report on subjects attending novel headspace services for young persons with emerging major mental disorders are followed longitudinally, with subsets recruited for more detailed neurobiological studies. Separately, we conduct a longitudinal study of adolescent twins, examining the patterns of emerging comorbidity between depressive, bipolar, psychotic and other substance-abuse related mental disorders. While clinical subjects with early phases of bipolar-type disorders are not readily differentiated from other significant unipolar disorders on clinical characteristics, they are separated by family history of bipolar disorder, some neuroimaging characteristics and a range of features suggesting circadian dysfunction. Evidence from the neuroimaging and circadian studies also suggest that distinct neurobiological features emerge progressively as subjects move from earlier to later stages of illness. The twin studies demonstrate that while motor activation and sleep disturbance features are common in adolescence, by themselves they are not indicative of bipolar or other major mental disorder. Patterns of overlap with other depressive and psychotic disorders suggest that more complex phenotypic presentations may be under stronger genetic control. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

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9th International Conference on Early Psychosis

Symposium Session 5 Monday November 17, 2:30–3:55 p.m., Concord B

Families Overcoming Risks and Building Opportunities for Wellbeing (FORBOW): a high-risk cohort multiple randomized controlled trial Rudolf Uher, Jill Cumby, Lynn McKenzie, Jessica Morash, Alexa Bagnell, Lukas Propper, Sabina Abidi, Barbara Pavlova, Martin Alda Department of Psychiatry, Dalhousie University, and the Capital District Health Authority, Halifax, Nova Scotia, Canada

What can we learn from familial high risk studies: possibilities for intervention in the premorbid phase? New arena for early intervention Chair: Anne Thorup, University of Copenhagen; co-chair: Larry Seidman, Harvard Medical School; speakers: Larry Seidman, Rudolf Uher, Manon HJ Hillegers, Ditte Ellersgaard Early detection and early intervention is a must if we want to improve the prediction and treatment of severe mental illnesses like schizophrenia and bipolar disorder. Intervention strategies for reducing disability and preventing psychotic disorders have evolved from first episode to ultra-high risk to earlier phases of pre-psychotic illness. Family high risk studies of children with parents with mental illnesses can identify early precursors of mental illness at various ages, and we can gain more knowledge about developmental trajectories of behavior and social functioning, symptom dimensions, cognition, and of structural brain changes. These data can lead to targets and strategies for treatment. Four different family high risk studies will be presented in this symposium representing a new generation of studies from around the world.

Background: Offspring of parents with major mood and psychotic disorders have a 1 in 3 risk of developing a severe mental illness themselves. Early antecedents including anxiety, affective lability, basic symptoms and psychotic like experiences precede and predict the development of severe mental illness. The combination of family history and antecedents marks a very-high risk population in need of pre-emptive early interventions. Methods: FORBOW enrolls and annually assessed high risk offspring of parents with schizophrenia, bipolar disorder and severe recurrent depression across a broad age range (age 3 to 21 years). One in two offspring with one or more antecedents are randomly selected to be offered the Skills for Wellness (SWELL) individual cognitive-behavioral intervention, in a cohort-multiple randomized control trial design. Results: Of the first 100 high-risk offspring, 35% had anxiety disorders, 30% had significant affective lability, 17% had high-risk basic symptoms profiles and 16% had psychotic-like experiences. In total, 57% had one or more antecedents and 46% were eligible for the SWELL intervention, which will be offered to the first participants in May 2013. Conclusions: A large proportion of offspring of parents with major mood and psychotic disorders experience early psychopathological antecedents. The early experience with SWELL intervention, including its acceptability in non-treatment seeking youth will be reported.

Clinical, neurocognitive, and neuroimaging characteristics of adolescent bipolar and schizophrenia offspring Implications of developmental impairments for early interventions to prevent psychosis

Manon HJ Hillegers, Anna de Jong, Matthijs Vink, Marloes Vleeschouwer, Ruby Pouwels, Eske M Derks, Rene S Kahn

Larry Seidman

Department of Psychiatry, University Medical Centre Utrecht, Utrecht, The Netherlands, Brain Center Rudolf Magnus, Utrecht, The Netherlands

Harvard Medical School, Massachusetts Mental Health Center Division of Public Psychiatry, Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Background: Intervention strategies for reducing disability and preventing psychotic disorders have evolved from first episode to ultra-high risk to earlier phases of pre-psychotic illness. Which potential intervention targets are highlighted by familial high-risk (FHR) studies? Methods: Results from our two recent quantitative and qualitative reviews on neurocognition and brain imaging (MRI) in youth at FHR for psychosis, and results of three of our own studies characterizing youth at FHR will be summarized, focusing on neurocognition and behavior from the prenatal period to age 25. The studies are the New England Family Study (NEFS), prenatal to age 7 (N = 281 FHR, 185 controls), the Harvard Adolescent FHR Study ages 13–25 (N = 41 FHR, 55 controls), and a new, ongoing FHR study, children ages 7–12. Results: Brain structural alterations are present as young as 7 years of age, and are most robust in prefrontal cortex (PFC) and hippocampus. Functional MRI studies reliably implicate PFC and the temporal cortical dysfunction. Cognition (as young as age 3) and motor integration problems observed in the first year of life are found primarily in offspring of individuals with schizophrenia, more than affective psychoses. Evidence is strong for impaired IQ, declarative and working memory, and some executive functions, (e.g., organizational ability) in FHR youth. Conclusions: Impairments are present in a substantial percentage of FHR youth, of whom roughly 10% go on to develop psychosis, and another 40% have psychiatric disorders. Discussion of earlier interventions, including cognitive enhancement are explored within the context of an evolving framework of ethical considerations.

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Background: Bipolar disorder and schizophrenia are severe neuropsychiatric disorders. Several authors have defended the notion that schizophrenia and bipolar disorders should be studied jointly, given that they have common clinical, genetic and cognitive characteristics (Craddock et al., 2006). To our knowledge, only one study to date has jointly analysed child and adolescent offspring of schizophrenia and bipolar disorder patients employing DSM-IV criteria (Maziade et al., 2008). The objective of the Dutch Bipolar and Schizophrenia Offspring Study (DBSOS) is to identify clinical, neurocognitive and brain function characteristics in bipolar and schizophrenia offspring compared with community controls that may allow us to define common and specific vulnerability markers for both disorders. Methods: 92 BD and 33 SZ offspring and 46 controls, aged between 8 and 16 years (mean age 12.9), were assessed for psychopathology (K-SADS-PL), (CBCL/6-18) and cognitive functioning (WISC III). A subsample of medication naïve BD, SZ offspring performed a reward task and an affective picture task while being scanned with functional MRI (3T). Results: Both BD- and SZ offspring show a significant higher prevalence of psychopathology and lower IQ than controls. Compared to aged matched controls and BD offspring, particular SZ offspring show impaired reward and affective processing. Together with abnormal orbitofrontal activation, these findings indicate abnormal functioning of the frontalsubcortical network in adolescent SZ offspring, but not in BD offspring. Conclusions: The increased prevalence of psychopathology in SZ offspring might be an nonspecific early clinical manifestation of severe mental illness and is represented by an impaired frontal-subcortical network. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Categorical and dimensional psychopathology among 7-year-old offspring of parents with schizophrenia or bipolar disorder in The Danish High Risk and Resilience Study – VIA 7 Ditte Ellersgaard,1,2 Anne Thorup,1,2 Jens R Jepsen,1,2 Birgitte K Burton,2,3 Nicoline Hemager,1,2 Camilla Christiani,1,2 Katrine S Spang,1,3 Aja Greve,2,4 Ditte Gantriis,2,4 Ole Mors,2,4 Kerstin J Plessen,3,5 Merete Nordentoft,1,2,5 1 Mental Health Services – Capital Region of Denmark, Mental Health Centre, 2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 3Mental Health Services – Capital Region of Denmark, Mental Health Centre for Child and Adolescent Psychiatry, 4Research Department P, Aarhus University Hospital, Risskov, Denmark, 5University of Copenhagen – Faculty of Health and Medical Sciences, Copenhagen, Denmark

Objective: Typically, the age of onset for schizophrenia and bipolar disorder is in early adulthood. However, previous high risk studies have found that offspring of patients with these disorders have a higher prevalence of psychiatric disturbances during childhood relative to peers. We aim to map psychopathology among 7-year-old children at familial high risk for developing schizophrenia or bipolar disorder. Methods: We are establishing a stratified cohort of 500 children aged 7 with one, two or none of the parents registered with schizophrenia spectrum psychosis or bipolar disorder in the Danish national registers. By using Danish national registers, we are able to form a representative cohort with high risk children and controls being matched on age, gender and urbanicity. Furthermore, the use of registers provides access to currently ill parents as well as parents remitted for several years. Psychopathology of the children is investigated from multiple perspectives and sources. Psychopathology is assessed categorically with ‘best estimate lifetime diagnoses’ using ‘Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime Version’ (K-SADS-PL). Dimensional psychopathology is measured with various rating scales (i.e. ADHD-Rating Scale and Child Behaviour Checklist) and questionnaires assessed by primary caregivers, teachers, the children themselves and by direct observation. Psychosis-like symptoms (PLIKS) are assessed with the psychosis supplement from K-SADS-PL. Results: Data collection started in December 2012 and is due to be completed by December 2015. By April 2014, 195 families were included in the study and 158 families had completed the assessment. Preliminary data will be presented.

Symposium Session 6 Monday November 17, 2:30–3:55 p.m., Concord C

Outcome: This symposium will present an outline of the successes in developing and implementing the Meaningful Lives statement. It will also highlight challenges that remain as well as describe a number of innovations that are being made to IPS to make it more relevant and successful for young people with psychosis.

Helping young people with psychosis back into education and work: how much progress has been made in realising the goals of the Meaningful Lives International Consensus statement (iFEVR 2008)? Jo Smith,1 Miles Rinaldi,2 Eoin Killackey,3,4 1

Worcestershire Early Intervention (EI) Service, Worcestershire Health and Care NHS Trust and University of Worcester, Worcester, UK, 2South West London and St Georges Mental Health NHS Trust, London, UK, 3Orygen Youth Health Research Centre, 4Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia Background: Supporting young people to achieve educational qualifications and secure employment is critical to longer term functional, social and health outcomes and should be a core component of EI service interventions. In 2008, this was identified as an area for international concern in the EI community requiring collective action (iFEVR 2010). Method: This paper will provide a systematic review of and update from published international research and policy papers specifically relating to the implementation and evaluation of supported education and employment initiatives in EI services over the last 6 years since the Meaningful Lives International Consensus statement was declared in 2008 (iFEVR 2010). Results: The review revealed the implementation of Individual Placement and Support (IPS) within EIP teams is most effective for young people, leads to significantly better education and employment outcomes (Rinaldi et al., 2010), can be embedded successfully into EIP teams (AbdelBakri et al., 2013) and is cost-effective (Knapp et al., 2014; Park et al., 2014). The review identified new evidence about the appropriate timing of supported employment intervention (Alvarez Jiminez 2012) and factors supporting successful implementation within EI practice (Dudley et al., 2014; Craig et al., 2014) as well as informal data on a growing international impact across countries. Conclusions: This review highlights progress to date and current implementation challenges in ensuring supported education and employment are given the priority they need to have if we are to successfully support young people with psychosis back into education, work and ‘ordinary lives’.

Not dreaming anymore: IPS employment and education in a national early psychosis system in Australia Eoin Killackey1,2

Supported education and employment initiatives in early onset psychosis Chair: Eoin Killackey, Orygen Youth Health Research Centre; speakers: Jo Smith, Eoin Killackey, Miles Rinaldi, Gina Chinnery Background: Individual Placement and Support (IPS) is an evidencebased intervention to help people with first episode psychosis (FEP) return to work. The International First Episode Vocational Recovery (iFEVR) group formed around this issue and in 2008 published the Meaningful Lives Consensus Statement. This statement highlighted the issues, the research base at the time and raised a number of goals to assist young people with psychosis to achieve meaningful lives through the fulfilment of their educational, training and employment aspirations. Aims and Objectives: This symposium will highlight development in this field since 2008. Through four related presentations, it will examine progress made in the realisation of the goals of the Meaningful Lives statement, in both research and implementation into practice. It will then describe the expansion of IPS to incorporate education and describe then process by which IPS implementation is being achieved on a national level in early psychosis services in Australia. Two further presentations will examine specific adaptations to IPS in order to further bolster outcomes. These will include a psychological addition to IPS and an adaptation in the focus of IPS from jobs to career. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

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Orygen Youth Health Research Centre, 2Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia Background: Individual Placement and Support (IPS) is an evidence based employment intervention. A number of studies have now shown the effectiveness of IPS in returning young people with first episode psychosis (FEP) to employment and education. However, there has been less focus on the educational outcomes, and there is little known about the systematic national implementation of IPS. This presentation will address both of these elements. Method: Two RCTs of IPS and an uncontrolled study of IPS for education specifically have been conducted. Results from these and other studies have formed the basis for policy submissions. Results: In a general IPS intervention for FEP, employment outcomes are greater than educational outcomes. However, when IPS is adapted to education exclusively, results strongly indicate the potential for IPS for education to be a stand-alone intervention. Policy submissions based on these and other results have led to IPS being a required component of the new national Early Psychosis system, currently being developed in Australia. Conclusion: 6 years after the launch of the Meaningful Lives statement, evidence produced in trials of IPS in FEP is being used in national mental health reform in Australia. This presentation will describe how that happened.

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9th International Conference on Early Psychosis The role of psychological factors in enhancing the impact of supported employment initiatives 1

2

3

4

5

Miles Rinaldi, Tom Craig, Swaran Singh, Jo Smith, Geoff Shepherd 1

South West London & St George’s Mental Health NHS Trust, London, UK, King’s College, Institute of Psychiatry, London, UK, 3Warwick Medical School, Warwick, UK, 4Worcestershire Early Intervention Service, Worcestershire, UK, 5Centre for Mental Health, London, UK 2

Background: Supported Employment (SE) has been shown in numerous controlled trials to be the most effective intervention for helping patients return to paid employment but is poorly implemented in practice because of scepticism and ambivalence of clinical staff. Objectives: To see whether a motivational intervention directed at clinical staff can improve occupational outcomes for patients following a first episode of psychosis. Methods: Two of four early intervention teams in the UK that offer supported employment (SE) as part of their clinical service were randomised to receive additional motivational training (MT) for clinicians focused on attitudinal barriers to employment. Occupational outcomes of patients in these teams were evaluated at 6 and 12 months. Results: 159/300 patients in these teams consented to the research. Occupational outcomes obtained for 149 (94%) at 6 months and 136 (85%) at 12 months follow-up. More patients in the MT intervention teams than in the SE only teams achieved employment by 6 months (25/76 vs. 9/73). A random effects logistic regression accounting for clustering by care coordinator and adjusted for the participant’s sex, ethnicity, educational and employment history, PANSS and GAF scores confirmed superiority of the MT+MI intervention (OR 4.5 95%, CI 2.2 to 12.4). Comparable results were obtained for 12-month outcomes. Conclusions: Occupational outcomes of an SE programme were enhanced by addressing clinical ambivalence about supporting their patients back into work.

More than a job for today: career focused IPS and young people with psychosis Gina Chinnery Orygen Youth Health Clinical Program, Australia Background: The onset of psychosis occurs when people are engaging in important developmental tasks. One of these is vocational development: finishing secondary school; moving to further study or training; and entering the workforce. Individual Placement and Support (IPS) is an effective intervention to address employment and education in young people with psychosis. However, a number of challenges exist that need still to be addressed. These include factors related to the client, and external factors such as a changing world of work in which job security is diminishing. This results in employers favouring temporary or contract positions, as opposed to permanent roles.

Symposium Session 7 Monday November 17, 4:30–5:55 p.m., Concord A Social cognition in people at clinical high risk for psychosis: meta-analysis, neural basis and predictive relevance Chair: Andre Aleman, University of Groningen; co-chair: Christine Hooker, Harvard University; speakers: Marieke Pijnenborg, Christine Hooker, Jun Soo Kwon, Kelly Allott In this symposium, we take stock of recent advancements in the study of social cognition in people at clinical high risk for psychosis. This area has been relatively underinvestagated in comparison to cognitive functioning and structural brain measures. First, a meta-analysis will be presented of social cognitive performance in people at clinical high risk for psychosis. Based on pooled data from 15 studies, it is concluded that theory of mind, recognition of affective prosody and facial affect are impaired. Second, fMRI data will be presented of simulation (the ability to use one’s own experience to understand what the other person is feeling) in at-risk subjects. Associations with social functioning were also investigated. Day-today social behavior was assessed with a daily-diary in which participants reported the number and nature of social interactions each day. The results revealed predictive value of somatosensory cortex activation. The third presenter will discuss findings from a longitudinal study in which neurocognitive and social performance were assessed at baseline and after 2 years in a clinical high risk sample. Finally, a study will be presented comparing emotion recognition abilities in people at clinical high risk as compared to first-degree relatives of schizophrenia patients to elucidate its possible role as an endophenotype. Whether emotion recognition deficits would predict transition to psychosis was also investigated. Whereas deficits in negative emotion recognition were found to qualify as an endophenotype for psychopathology, the findings indicated that misattribution of neutral affect and fear recognition may represent state markers of psychosis onset.

Social cognition in people with an ultra-high risk for psychosis: a quantitative review Marieke Pijnenborg1,2 1

University of Groningen, Netherlands

2

Mental Health Center GGZ Drenthe, The

Background: People with an “ultra high risk” (UHR) for psychosis display deficits in various cognitive domains, including social cognition. This meta-analysis summarizes empirical studies on social cognition in the UHR phase in four domains: emotion perception (recognition of facial affect and prosody), theory of mind, social perception and attribution style.

Method: By adapting IPS, which has traditionally been focussed on employment outcomes, to also include educational outcomes, a broader role of career planning rather than job placement can be developed.

Methods: Eligible studies were identified through computerized searches of the Medline (PubMed) and PsycINFO bibliographic databases during 1995 to 2014. Search terms included combinations of the following: early recognition, OR clinical high risk OR ARMS OR UHR OR prodrom*AND psychos* AND social cognition OR emotion OR theory of mind OR social rules and OR attribution style. References from studies retrieved were reviewed to identify additional articles.

Results: This presentation will describe a means of embedding ongoing career development in the IPS process as a way of reducing placement dropout rates. Supporting and regularly reviewing an individual’s career development plan ensures people with mental illness remain competitive in a rapidly evolving employment market while also achieving milestones and moving forward on their career journey.

Results: Fifteen relevant studies were identified. Six reported on facial affect recognition, three on affective prosody, seven on theory of mind, two on social rules and two on attribution style. Overall effect sizes for categories with more than two studies were calculated. We found a moderate and significant effect sizes for facial affect recognition, prosody, and theory of mind, indicating impaired performance in the UHR phase.

Conclusion: Employers in the modern world of work also expect employees to manage multiple tasks and undertake ongoing learning and development to maintain currency in their workplace; tasks that can be difficult for people managing mental illness. By adapting IPS to include education and a career rather than job outcome focus, greater outcomes can be achieved for young people with psychosis.

Discussion: Impaired theory of mind, recognition of affective prosody and facial affect are reliably found in people with an at risk mental state. Two studies examined whether impaired theory of mind is predictive for transition. Evidence from these studies is mixed, it has been suggested that general intellectual abilities may mediate this relationship. More research is needed on social perception and attribution style in the UHR phase.

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© 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Neural mechanisms that support social relationships in clinical high risk for psychosis

Emotion recognition in individuals at ultra-high risk for psychosis: a possible endophenotype?

Christine Hooker

Kelly Allott

Department of Psychology, Harvard University, USA

Orygen Youth Health Research Centre, Centre for Youth Mental Health, The University of Melbourne, Australia

Social problems prospectively predict the onset of psychosis and the severity of schizophrenia, suggesting that social problems could be an effective target for prevention and treatment, yet the underlying causes are unknown. Successful social relationships require the ability to understand and empathize with others. Simulation facilitates this ability and involves using one’s own experience to understand what the other person is feeling. Here, we investigate the neural mechanisms of simulation and their relationship to social functioning in participants at clinical high risk (CHR) for psychosis. Methods: During fMRI scanning, 21 CHR and 19 healthy control (HC) participants viewed videos of another person experiencing a hand injury (e.g. being cut by a knife). Participants were then asked how unpleasant that injury would be for them. We hypothesized that simulation during this question would result in neural activity in the hand region of somatosensory cortex and that the amount of activity would predict empathy and related social processes in daily life. Day-to-day social behavior was assessed with a daily-diary in which participants reported the number and nature of social interactions each day. Results: Across both CHR and HC participants the amount of somatosensory cortex activity prospectively predicted empathy, perspective-taking, and other aspects of social functioning over the following 7-days. Conclusions: Results suggest that simulation is an effective strategy to understand others, and, deficits in this process contribute to social functioning problems. The data also suggest that treatment targeting simulation and its underlying neural substrates could be functionally beneficial and assessed with fMRI.

Neurocognitive and social cognitive performances in people at clinical high risk for psychosis: a 2-year follow-up study Jun Soo Kwon

Objective: Emotion recognition (ER) is found to be impaired in chronic schizophrenia, first-episode psychosis (FEP) and individuals at ultra-high risk (UHR) for developing a psychotic disorder, suggesting it may be a vulnerability marker. The aim of this presentation is to examine the evidence for ER as an endophenotype for psychotic disorder by investigating (1) the specific ER impairments in UHR; (2) ER in unaffected first-degree relatives (FDR) of people with FEP; and (3) ER as a predictor of transition to a psychotic disorder in UHR. Methods: Participants from the following four groups completed facial and prosody emotion recognition tasks: 79 UHR, 30 FEP, 27 FDR and 30 healthy controls. Transition to psychotic disorder over 12 months was examined in a subset of the UHR group (n = 37). Results: Compared to healthy controls, UHR participants displayed significant deficits in recognising fear and sadness across both modalities and anger in voices. These deficits were comparable to the FEP participants. Similarly, compared to healthy controls, FDRs performed significantly worse in fear recognition in faces and anger recognition in voices. However, poorer neutral emotion recognition and better recognition of fearful emotions was predictive of transition to a psychotic disorder within 12 months in the UHR individuals. Conclusions: The findings suggest that deficits in negative emotion recognition are an endophenotype for psychopathology, but are not predictive of transition to a psychotic disorder. Misattribution of neutral affect and fear recognition may represent state markers of psychosis onset.

Symposium Session 8 Monday November 17, 4:30–5:55 p.m., Concord B

Seoul National University College of Medicine, South Korea Background: Recently, neurocognitive and social cognitive dysfunctions are frequently reported in individuals at clinical high risk (CHR) for psychosis. However, longitudinal research is needed to confirm whether this is a specific marker for the transit to psychosis and remit from initial high risk state. Method: Seventy-five CHR subjects and 61 healthy controls were recruited, and their neurocognitive and theory of mind task performances were assessed. CHR subjects were divided into converter, remitter, and nonremitter groups according to their clinical state during a 12 to 24 follow-up. Results: At baseline, we found that the neurocognitive performances including executive functions, attention, verbal memory, verbal fluency, visual memory were significantly differences among the group. On the other hand, converters showed significantly reduced performances in theory of mind task compared with another groups, however, there were no significant difference among the remitter, non-remitter, and healthy controls. In longitudinally, we found that performance on semantic fluency was significantly improved in remitters but declined in non-remitters over the 2-year follow-up. However, there was no significant difference in theory of mind task performances between the groups during the follow-up period. Conclusion: We suggest that the social cognitive deficits could be a specific marker for vulnerability for psychosis, while semantic fluency is associated with conversion to psychosis or continuing clinical high risk state. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Facing new challenges in the evolution of early intervention services: research and an agenda for action Chair: Ashok Malla, McGill University; speakers: Ashok Malla, Nikolai Albert, Srividya Iyer, Charlotte Connor For over a decade, there has been a proliferation of Early Intervention (EI) services within the mental health care systems of most economically advanced countries. While this growth of a comprehensive model of service delivery to patients presenting with a first episode of psychosis (FEP) is based on and supported by convincing evidence from controlled and uncontrolled studies, several challenges have emerged and remain to be addressed. In this symposium, clinicians and researchers will attempt to address at least three of these challenges, namely (a) a general failure to reduce delay in treatment and to positively alter pathways to care for majority of young people with FEP; (b) defining an optimum length of EI services to address the failure to sustain gains made in the first 2 years of treatment in an EI service; and (c) addressing variation in needs of ethnic minorities, first and second generation immigrant youth and different cultural groups, especially in urban areas of economically developed societies as well as issues related to EI service development in low and middle income countries. Each presentation will address one or more of these issues from the perspective of their respective jurisdiction (the UK, Denmark, Canada and India) and attempts that are currently being made to address these challenges.

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9th International Conference on Early Psychosis Challenges of altering pathways to care and length of adequate EI services: two controlled trials from Canada

Limited attention to diversity and context: how it poses challenges in service delivery for first-episode psychosis and recommendations

Ashok Malla,1,2 Ridha Joober,1,2 Srividya Iyer,1,2 Norbert Schmitz,1,2 Ross Norman,3 Thomas Brown,1,2 Eric Jarvis,1,4 Amal Abdel-Baki,5,6 Howard Margolese1,7

Srividya Iyer,1,2 Megan Pope,1,2 Heleen Loohuis,2 Gina Marandola,2 Connie Lee,2 Thara Rangaswamy,3 Ashok Malla1,2

1

1

McGill University, Montréal, Canada, 2Douglas Mental Health University Institute, Montréal, Canada, 3Western University, London, Ontario, Canada, 4Jewish General Hospital, Montréal, Canada, 5Université de Montréal, Montréal, Canada, 6l’Hopital Notre Dame, Montréal, Canada, 7McGill University Health Centre, Montréal, Canada In this presentation, two challenges, namely, failure to influence pathways to care and optimum length of EI service, will be addressed. Most patients with a first episode of psychosis (FEP) make their first contact with primary care services but few get into an EI service directly, resulting in systemic delay. We report the results of a study evaluating the impact of direct training of all potential points of contact by new patients on the referral portion of duration of untreated psychosis (DUP-R). Following the intervention, the number of referrals from primary care services (health and education) increased substantially but majority of these did not have a FEP; DUP-R remained longest for patients referred from primary care and shortest for patients presenting directly to the hospital emergency service; there was little change in the pathways to care for patients who presented first to primary care; and patients with very long DUP were younger and most likely to have been referred from primary care. For the challenge of duration of EI service, we will present the methodology and preliminary results of a single blind RCT comparing extension of an EI service (N = 111) from 2 to 5 years compared to routine care (N = 109), following first 2 years of EI service. Preliminary data suggest that a higher proportion of patients drop out of the routine care arm (51/109, 47%) compared to the EI (16/108, 15%) arm and obstacles in transferring patients to routine care and its significance for interpretation of results are discussed.

McGill University, Montréal, Canada, 2Douglas Mental Health University Institute, Montréal, Canada, 3Schizophrenia Research Foundation, Chennai, India Substantial evidence supports the efficacy of early intervention (EI) services for FEP. Most EI services cater to patients and families from diverse social, cultural, and ethnic backgrounds. Yet, relatively little attention has been paid to how this diversity shapes the EI experience. Similarly, little is known about the suitability and transportability of traditional EI services across contexts, e.g., in a developing country. This symposium segment will highlight these gaps using relevant literature and quantitative and qualitative findings. Our first source of insights is an ongoing CanadaIndia FEP project (involving a site each in Montreal and Chennai). Over 100 persons with FEP have entered the clinical-research FEP program in India in recent times. The program and its clients’ and families’ experiences have highlighted critical issues about EI in a context like India (e.g., some families wish to initiate treatment via concealed medications without their loves ones’ consent). Our second source of insights is an examination, in the Canadian context, of how ethnicity influences family service engagement (i.e., participation in screening and psychoeducation; views regarding the relative roles of patients, families and governments) and the challenges of serving recent immigrants (i.e., visa status, health insurance, financial concerns, poor family and social support, poor service engagement, etc.). We will show that these gaps must be addressed if the needs of diverse service users communities considering EI services development are to be met. We will propose a clinical, service, policy, and research agenda for the future to better address these knowledge and implementation gaps.

How long should a specialized assertive early intervention program last? Nikolai Albert, Heidi Jensen, Marianne Melau, Carsten Hjorthøj, Merete Nordentoft Mental Health Center Copenhagen, University of Copenhagen, Denmark Since the discovery of antipsychotic treatment, development of specialised, assertive programmes involving families represents the most significant progress in treatment. The Danish OPUS I trial was the largest trial in first-episode psychosis in the world. The OPUS I trial found that it was possible to improve clinical outcome in first-episode psychosis through a specialised early intervention service (SEI). However, the 5-year follow-up showed that, except from OPUS-patients being less institutionalized, the positive clinical effects were not sustained, when the intensive treatment was terminated. The question arose whether 2 years of SEI were too short. This represents a clear rationale for the OPUS II-trial, investigating if 5 years of SEI is more appropriate to ensure long lasting clinical effect. Method: In the OPUS II trial, based on calculation of sample size, after 2 years of OPUS treatment, 400 patients were randomised to 3 years further OPUS treatment versus transfer to standard treatment. The OPUS II trial complies with the extended CONSORT criteria. The primary outcome measure is negative symptoms, which are the most disabling symptoms, closely associated to labour market affiliation. The results will be of significant interest on the societal level, as they will guide health care providers in the implementation of specialised early intervention services both in Denmark and in other countries. Results: Study design and results of the baseline assessment will be presented and compared to the results of OPUS I trial. Discussion: It will be discussed which are the crucial elements in specialized assertive early intervention.

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Changing care pathways to early intervention in psychosis teams and their impact on DUP: results of a public health trial in Birmingham, UK Charlotte Connor,1 Max Birchwood1,2 1

Birmingham & Solihull Mental Health NHS Trust Research & Development Unit, 2Warwick University, UK

Public health initiatives to reduce duration of untreated psychosis (DUP) have met with mixed results. Systematic reviews suggest that a greater focus on the individual sources of delay is needed to achieve sustainable reductions in DUP. In Birmingham, UK, we confirmed the two primary sources of delay responsible for long DUP: delays in help-seeking and delays within mental health services, particularly accessing early intervention teams. These findings suggested that interventions aimed at reducing DUP would require a multi-faceted approach targeting both delays. In order to examine this, we implemented a quasi-experimental public health trial, introducing a new youth access pathway into mental health services, with single referral to EIP teams, alongside a public health campaign targeted particularly at families. Comparison of DUP for young people accepted into EIP from the targeted intervention area with the ‘detection as usual’ area revealed a highly significant reduction in DUP of 81 days for those who received the public health campaign in addition to improved access to EIP (relative risk for the reduction in DUP for the intervention area = 0.736 (95% CI 0.350 to 0.893) p = 0.0039). Delays within mental health services were reduced by 63 days and help-seeking delays reduced by 82 days. These positive findings suggest changes in care pathways to EIP teams can have major benefits in reducing treatment delay and provide the foundations for a major trial. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA

Symposium Session 9 Monday November 17, 4:30–5:55 p.m., Concord C Symposium on case management: the art of engagement: focusing on what really matters to our clients Chair: Helen Lee, Institute of Mental Health; co-chair: Swapna Verma, Institute of Mental Health, DUKE (NUS); speakers: Helen Lee, Craig A Macneil, Hee Eon Choi, NKM Lau Case management is perhaps the most important component of an Early Intervention (EI) Service. One cannot downplay the significance of functional recovery especially when working with young people with firstepisode psychosis. Hence, many of the EI programs in Asia-Pacific have moved beyond looking at symptomatic remission to offering innovative and often path-breaking case management services geared toward maximizing engagement and improving quality of life. We have presenters from Melbourne, Singapore, Hong Kong and Korea sharing the successes and challenges in the implementation of their unique and culturally adaptive psychosocial interventions and models of care in case management.

Case management at the early psychosis prevention and intervention centre, Melbourne, Australia: the CBCM model Craig A Macneil,1 Frances Foster,2 Frank Hughes,3 Simon Dodd,2 Shona Francey,1 Jane Edwards,1 Patrick McGorry1 Early Psychosis Prevention and Intervention Centre, Orygen Youth Health, 2 Orygen Youth Health Research Centre, 3EPPIC National Support Program, Orygen Youth Health Research Centre, Australia Case management has been described as the “central pillar” of early psychosis services, providing clients and their families with a lead clinician who will oversee treatment, undertake therapeutic interventions, offer continuity of care, and provide advocacy. This presentation will focus on the model of case management that is being utilized by the multi-disciplinary team at the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. Specifically, this paper will focus on the cognitive behavioral case management (CBCM) approach, a phase- and developmental stage- specific intervention designed for young people experiencing first episode psychosis. This model acknowledges some of the challenges and opportunities inherent in working with a young, first episode population, including complexities around engagement, comorbidity, insight, risk of secondary morbidity, resilience, and opportunities for functional recovery. The presentation will report on the key concepts of the CBCM model, namely, flexibility, accessibility, capability, persistence, and optimism. It will also describe the key practical foci of the CBCM model including attending to the young person’s hierarchy of needs, engagement, formulation, treatment planning, risk assessment, psychoeducation, managing positive symptoms, medication, and supporting family and other carers. The presentation will conclude with recommendations for the further development of this model.

The development of case managers of the early psychosis intervention programme, Singapore Helen Lee, Lye Yin Poon, Swapna Verma Early Psychosis Intervention Programme, Institute of Mental Health, Singapore The Singapore Early Psychosis Intervention Programme (EPIP) was established up in April 2001 offering integrated, multi-disciplinary care to young people with first-episode psychosis. Over the years, our focus has moved from remission to recovery and the key linchpin in enabling this transformation has been our case management service. Case managers conduct bio-psycho-social assessments and provide interventions for our clients for a period of 3 years. They work collaboratively with community partners and a comprehensive phase-specific care plan is developed and continuity of holistic care is ensured across different stages of our clients’ recovery. Over the years, we have slowly evolved from emphasizing medication compliance and adherence to doctors’ appointments to focusing more on identification of clients’ strengths and improving functional recovery. Case managers now are equipped with knowledge and skills of various strengths-based models, such as solution focused brief therapy and acceptance and commitment therapy, and are encouraged to use these concepts and strategies. They are also more involved in family works where systemic approaches are necessary. Individual and group supervision sessions are provided to ensure competency. At this juncture, we cannot conclude with absolute certainty that this increased knowledge and skills have had a direct and positive impact on our clients’ recovery, however our case managers certainly feel more empowered and confident. The oral presentation will present our algorithms to illustrate the case managers’ role in each phase of our clients’ recovery. Our plans for the profession’s development will also be discussed. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Case-management models for early psychosis intervention in Asia Hee Eon Choi,1 Sang Jun Lee,1 Hong Jae Kim,1 Young Chul Chung1,2 1 Mental Health Promotion Center, Jeonju, South Korea, 2Chonbuk National University Hospital, Jeonju, South Korea

After 5 years from a first episode of schizophrenia, only few patients (13.7∼25.5%) are reported to have adequate social function. This findings stress the need to provide phase-specific psychosocial intervention to improve social function during the critical period. In 2010, a communitybased psychosocial intervention program, Mind Flower Service, was developed in Jeonju mental health promotion center in collaboration with Chonbuk National University Hospital. Initially, its contents were sending positive text message, lending best books selected for good mental health, financial support covering half expense for the class of personal development or physical exercise plus individual counseling. Recently, meta-cognition training (MCT) consisting of weekly nine sessions and mentor service were incorporated. We were interested in comparing short-term outcome between the group (n = 16) receiving basic services (text message, books, financial support and individual counseling) and the group (n = 15) with intensive service (basic services plus MCT). The measures were MetaCognitions Questionnaire 30 (MCQ-30), Psychosocial Inventory of Ego Strengths (PIES), paranoia scale, and Global Assessment of Functioning (GAF). The group with intensive service showed greater degree of improvement in the MCQ-30, and paranoia scale after the intervention. This remained significant after correction of baseline variables. The limitations are non-randomized, and open design. Implications and future development will be discussed.

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9th International Conference on Early Psychosis Psychosocial intervention: promoting functional recovery in adult patients with early psychosis: a recovery-oriented life coaching intervention

Identification of subgroups of schizophrenia patients with changes in either immune or growth factor and hormonal pathways

NKM Lau, WC Chang, SKW Chan, EHM Lee, CLM Hui, JJX Lin, MJQ Xu, RTY Cheung, EYH Chen

Nico van Beveren,1,8 Emanuel Schwarz,2 Jordan Ramsey,2 Markus Leweke,3,4,5 Matthias Rothermundt,5 Bernhard Bogerts,6 Johann Steiner,6 Paul Guest,2 Sabine Bahn2,7

The University of Hong Kong, Hong Kong

1

Disruptions in functioning are commonly reported in patients with psychosis. Apart from symptomatic remission, functioning is one of the most important indicators of recovery. Recent studies have consistently revealed that achievement of adequate functioning is a critical element signifying recovery. Although the majority of first-episode psychosis (FEP) patients achieve symptomatic remission after adequate antipsychotic treatment, a significant proportion of them still exhibit prominent functional impairment. Jockey Club Early Psychosis (JCEP) project is a specialized early intervention program in Hong Kong that provides 2–4 year phase-specific case management for adults presenting with FEP. To facilitate their early functional recovery, JCEP has developed a psychosocial intervention based on life coaching approach. This intervention includes 10 weekly structured group-based sessions incorporating cognitive-behavioral, motivational, and solution-focused therapeutic components. The program facilitates patients to undergo active change process via identification of achievable goals, formulation of action plans, provision of feedback and progress monitoring for goal attainment. It is strength-oriented and aims to facilitate patients to gain a sense of agency and to achieve sustained functional improvement via firstly, enhancing motivation, self-regulation and competence by positive reinforcement obtained from successive accomplishments of self-determined goals; secondly, providing an autonomy-supportive treatment environment with a context of recovery expectations; and thirdly, facilitating formation of supportive social network in group-based setting. Owing to an unmet therapeutic need for functional recovery in patients with early psychosis, group-based life coaching intervention serves as an innovative yet potentially promising psychosocial therapeutic approach that deserves systematic evaluation of its effectiveness in functional improvement

Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands, 2Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK, 3Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany, 4Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany, 5 Department of Psychiatry, University of Muenster, Muenster, Germany, 6 Department of Psychiatry, University of Magdeburg, Magdeburg, Germany, 7Department of Neuroscience, Erasmus University Medical Centre, Rotterdam, The Netherlands, 8Antes Center for Mental Health Care, Rotterdam, The Netherlands Schizophrenia is a heterogeneous disorder normally diagnosed using the Diagnostic and Statistical Manual of Mental Disorders criteria. However, these criteria do not necessarily reflect differences in underlying molecular abnormalities of the disorder. Here, we have used multiplexed immunoassay analyses to measure immune molecules, growth factors, and hormones important to schizophrenia in acutely ill antipsychotic-naive patients (n = 180) and matched controls (n = 398). We found that using the resulting molecular profiles, we were capable of separating schizophrenia patients into two significantly distinct subgroups with predominant molecular abnormalities in either immune molecules or growth factors and hormones. These molecular profiles were tested using an independent cohort, and this showed the same separation into two subgroups. This suggests that distinct abnormalities occur in specific molecular pathways in schizophrenia patients. This may be of relevance for intervention studies that specifically target particular molecular mechanisms and could be a first step to further define the complex schizophrenia syndrome based on molecular profiles.

Transdiagnostic exploration of the association of Toxoplasma gondii with psychiatric disorders: a systematic review and meta-analysis

Symposium Session 10 Tuesday November 18, 1:00–2:25 p.m., Concord A Neuroinflammation and infection in psychosis Chair: Arjen Sutterland, Academic Medical Centre, University of Amsterdam, The Netherlands; co-chair: Takashi Kanbayashi, Department of Psychiatry, Akita University School of Medicine, Akita, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan; speakers: Nico van Beveren, Arjen Sutterland, Takashi Kanbayashi, Fabienne Brilot In this symposium, research on several aspects of neuroinflammation and infection related to psychosis will be presented. We will present data on multiplexed immunoassay analyses in acutely ill antipsychotic-naive patients and matched controls to demonstrate that it’s possible to separate schizophrenia patients into two distinct subgroups with predominant abnormalities in either immune molecules or growth factors and hormones. The role of infection in psychosis will then be discussed through a meta analysis demonstrating that Toxoplasma gondii infection is associated not only with schizophrenia and showing subanalyses on the relevance of the intensity and timing of the infection in psychosis. We will then switch to another promising aspect of neuroimmunology with data on autoimmune antibodies in psychosis. First, findings on presence of antiNMDA-receptor antibodies in different patient groups (typical encephalitis, narcolepsy with psychotic features and schizophrenia) will be presented and discussed. Next, the case of autoantibodies targeting the Dopamine-2 receptor will be presented. Issues related to brain autoantibody detection, potential pathogenic mechanisms, and their relevance in early psychosis will then be discussed.

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Arjen Sutterland,1 Guillaume Fond,2 Anne Kuin,1 Maarten Koeter,1 Rene Lutter,1 Tom van Gool,1 Robert Yolken,3 Andrei Szoke,2 Marion Leboyer,2 Lieuwe de Haan1 1

Academic Medical Centre (AMC), Amsterdam, The Netherlands, 2Université Paris Est, Pôle de Psychiatrie du Groupe des Hôpitaux Universitaires de Mondor, DHU Pe-Psy, INSERM U955, Eq Psychiatrie Génétique, Fondation FondaMental Fondation de Coopération Scientifique en Santé mentale, F-94000 Créteil, France, 3Stanley Neurovirology Laboratory, Johns Hopkins School of Medicine, USA Many studies have investigated the association between Toxoplasma gondii (T. gondii) and schizophrenia. An updated meta-analysis in 2012 showed a significant odds ratio (OR) of 2.7. Currently, several studies have looked at the association between T. gondii and other psychiatric disorders as well, rendering exploration of diagnostic specificity possible. Furthermore, questions remain on the timing and nature of the infection. For this, PubMed, MEDLINE and PsychINFO were systematically searched by two reviewers to identify relevant studies that studied all major psychiatric disorders versus healthy controls in relation to T. gondii infection. Methodological quality, heterogeneity and risk of publication bias were assessed. A total of 2866 studies were found, from which 51 studies were finally included in our meta-analysis. Significant OR was found for schizophrenia (2.0), bipolar disorder (2.1), major depression (1.5), OCD (3.2) and addiction (2.1). Further exploration of the association between T. gondii and schizophrenia yielded a significant association of seropositivity before onset of psychosis (OR 1.4), with recent onset schizophrenia (1.8), IgM seropositivity (1.3) and with high antibody titers (3.2). When baseline exposure in the healthy control population increased, a significant decline of the association was found in a meta-regression analysis. These findings suggest that a T. gondii infection is not merely associated with psychosis and that in schizophrenia a reactivation of a latent T. gondii infection occurs. The strength of the association decreases with higher baseline exposure to T. gondii, but it remains significant. Several hypotheses remain open about the nature of this association. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Anti-NMDA-receptor antibodies detected in limbic encephalitis, schizophrenia and narcolepsy with psychotic symptoms 1,2

1

3

1

Takashi Kanbayashi, Kou Tsutsui, Keiko Tanaka, Aya Imanishi, Yohei Sagawa,1 Mayu Omokawa,1 Yuki Ohmori,1 Hiroaki Kusanagi,1 Seji Nishino,4 Testuo Shimizu1,2 1 Department of Psychiatry, Akita University School of Medicine, Akita, Japan, 2International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan, 3Department of Neurology, Kanazawa Medical University, Kanazawa, Japan, 4Sleep & Circadian Neurobiology Laboratory, Stanford Sleep Research Center, Stanford University, Palo Alto, California, USA

Introduction: Causative role of encephalitis in major psychotic features, dyskinesias (particularly orofacial), seizures, and autonomic and respiratory changes has been recently emphasized. These symptoms often occur in young females with ovarian teratomas and are frequently associated with serum and CSF autoantibodies to the NMDA receptor (NMDAR). Methods: The study included a total of 147 patients from age 12 to 72 and was carried out between Jan 1, 2005, and Dec 31, 2013. The patients were divided into the following three clinical groups for comparison. Group A: Patients with typical clinical characteristics of anti-NMDAR encephalitis. Group B: Patients with narcolepsy with severe psychosis. Group C: Patients with schizophrenia or schizoaffective disorders. Results: Seventeen out of 147 cases were anti-NMDAR antibody positive in typical encephalitis cases (group A: 7 of 15 cases) and cases in a broader range of psychiatric disorders including narcolepsy (group B: 4 of 12 cases) and schizophrenia (group C: 8 of 120 cases). Discussion: In addition to seven typical cases, we found 12 cases with anti-NMDAR antibody associated with various psychotic and sleep symptoms, which lack any noticeable clinical signs of encephalitis (seizures and autonomic symptoms) throughout the course of the disease episodes. Several groups measured this antibody in patients with schizophrenia. British group (Zandi2011), German group (Steiner2013) and us (Tsutsui2012) report an increase in the positivity of the antibody in the patients with schizophrenia, while Dalmau’s group (2011, 2012) did not. Therefore, the positivity of the antibody is still controversial, further detailed research is critical.

Symposium Session 11 Tuesday November 18, 1:00–2:25 p.m., Concord B Cannabis, alcohol, and other drugs in schizophrenia: dying from them, being admitted for them, and treating them Chair: Carsten Rygaard Hjorthøj, Copenhagen University Hospital, iPsych; speakers: Sagnik Bhattacharyya, Carsten Rygaard Hjorthøj, Marie Louise Drivsholm Østergaard, Kevin Madigan Substance use disorders remain a core problem in schizophrenia, despite many efforts to understand and treat them better. Cannabis in particular has received particular research in this group of effort, with previous research indicating possible causal links, as well as associations with psychotic symptoms, psychotic relapses, and non-adherence to medication. The association between cannabis use and hospitalization, mortality, and suicidal behavior, on the other hand, is largely unstudied, with only one or two small studies on the subject. Conversely, quite a few studies have attempted to treat comorbid cannabis use disorders in schizophrenia, but without much success. The present symposium will provide the latest updated knowledge on these areas, as summarized below: (1) in the first presentation, the effect of cannabis on readmission in first-episode psychosis is examined in two cohorts from London. (2) In the second presentation, the effect of cannabis and other substance use disorders on mortality in schizophrenia is examined using nationwide Danish registers. (3) In the third presentation, the effect of cannabis and other substance use disorders on both fatal and non-fatal suicide attempts is examined using nationwide Danish registers. (4) In the fourth presentation, results from a Delphi study are presented, detailing an international consensusapproach to developing new interventions for comorbid cannabis use disorder and schizophrenia.

Effect of comorbid cannabis use on risk of readmission in firstepisode psychosis: data from two cohorts employing complementary methodology Sagnik Bhattacharyya

Autoantibodies in autoimmune neuropsychiatric disorders and early psychosis Fabienne Brilot,1 Karrnan Pathmanandavel,1 Jean Starling,2 Nese Sinmaz,1 Vera Merheb,1 Sudarshini Ramanathan,1 Shekeeb Mohammad,1 Shehkar Pillai,1 Russel Dale1 1 Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at The Children’s Hospital at Westmead, University of Sydney, Australia, 2The Walker Unit, Concord Centre for Mental Health, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Australia

Recently, autoantibodies have been detected in defined treatable forms of autoimmune encephalitic disorders. Targets of these autoantibodies are neuronal surface receptors or synaptic proteins essential to brain physiology, such as N-Methyl D-Aspartate Receptor (NMDAR), or Dopamine-2 Receptor (D2R). These autoantibodies usually target extracellular domains and are generally detected in patients benefiting from immunosuppressive therapies. Although they have been initially detected in patients with neurological diseases, the presence of psychiatric features in these patients have prompted neuroimmunologists to explore their presence in schizophrenia and early psychosis. In this symposium, we will use the specific case of autoantibodies targeting the D2R, whose blockade is key to the activity of most clinically effective antipsychotics, to discuss issues related to brain autoantibody detection, potential pathogenic mechanisms, and their relevance in early psychosis. The study of autoantibody response in early psychosis may provide valuable insight into the definition of an autoimmune subgroup that is clinically and potentially pathologically separate, and that could benefit from immune suppression. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, UK Use of cannabis, the most commonly used illicit drug worldwide, has been linked to increased risk of relapse of illness in patients with psychosis who continue to use the drug. However, most studies investigating the effect of cannabis use on outcome are limited by, either a small sample size, short follow-up duration or outcome measures that rely on change of symptom severity. The purpose of this presentation is to present the results from two cohorts of patients with first episode psychosis (FEP) in South London, investigating the effects of cannabis use at presentation as well as ongoing use on subsequent admission to hospital, employing complementary approaches. Methods: Cohort 1 examined the electronic health records of over 2000 patients with FEP using natural language processing to investigate the effect of documented cannabis use around onset of illness on risk of subsequent hospital admission. Cohort 2 investigated the effect of ongoing cannabis use on hospital admission in a prospectively recruited FEP cohort (n = 95) followed-up through face-to-face interviews. Logistic and linear regression analyses were carried out. Results: Odds of readmission to hospital was significantly greater in FEP patients with history of cannabis use at onset of illness. Odds of readmission and number of readmissions were significantly greater and time to readmission significantly shorter in those FEP patients with ongoing cannabis use during follow-up period. Conclusions: Data from these prospective cohorts employing complementary approaches highlight the importance of ongoing cannabis use on risk of readmission in psychosis and suggest the need for prevention strategies.

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9th International Conference on Early Psychosis Mortality attributable to alcohol and substance use disorders in people with schizophrenia Carsten Rygaard Hjorthøj,1,2 Marie Louise Drivsholm Østergaard,1,2 Nanna Gilliam Toftdahl,1,2 Annette Erlangsen,1,2 Michael Eriksen Benros,1,2 Jon Trærup Andersen,3,4 Merete Nordentoft1,2 1

Copenhagen University Hospital, Mental Health Center Copenhagen, 2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 3Copenhagen University Hospital, Rigshospitalet, Laboratory of Clinical Pharmacology Q7642, 4Department of Clinical Pharmacology, Bispebjerg Hospital, Denmark Introduction: People with schizophrenia have higher rates of misuse of alcohol, cannabis, and other illicit substances than the background population. They are also at severely increased risk of early death. The association between substance use and mortality in schizophrenia, however, is not well-established. Methods: We linked nationwide Danish registers for people born in Denmark from 1955 onwards. Hazard ratios (HR) for both all-cause and cause-specific mortality attributable to different substance use disorders were estimated using Cox regression. Results: There were 41,470 incident cases of schizophrenia in the sample, and 4,616 deaths. For all-cause mortality, all types of substance use disorders increased risk of dying, HR = 1.79 (1.56–2.05) for exclusive misuse of hard drugs, followed by HR = 1.53 (1.41–1.66) for exclusive misuse of alcohol, and HR = 1.24 (1.04–1.79) for exclusive misuse of cannabis. Combinations of two/three types of misuse increased the HR further. Associations with suicide were less clear, with perhaps a reduced risk of suicide in people with misuse of alcohol. Risk of deaths from accidents or respiratory-organs illnesses was increased for all types of substance misuse. Alcohol increased the risk of dying from causes in the cardiovascular or digestive organs. None of the three types of misuse increased the risk of dying from malignant tumors outside the respiratory system.

Intervention development for cannabis dependence in the early phase of psychosis: creating consensus amongst local, national and international experts using a modified Delphi method Kevin Madigan,1,2 Stephen O’Rourke,1 John Waddington,2 Mary Clarke3 1

Detect Early Intervention in Psychosis Service, Dublin, Ireland, 2Royal College of Surgeons in Ireland, 3University College Dublin, Ireland Background: Substance use is recognised as the most common co morbidity of psychosis, with cannabis the substance used most often. A recent 5-year follow-up study of individuals with a first episode psychosis demonstrated that those who continued to use cannabis experienced more psychotic symptoms and poorer functioning. Thirty-two randomised controlled trials have failed to support evidence for an effective intervention to improve outcomes, most experiencing difficulties in recruitment and engagement. Aim: The aim of this study is to use a modified version of the Delphi method as an innovative way to consult with experts from various fields to gather their opinions through an iterative process and reach a consensus as to which interventions are most likely to engage and improve outcomes for people with early phase psychosis and comorbid cannabis abuse or dependence. Methodology: Participants are selected through the use of purposive sampling based on their expert knowledge in the areas of psychosis and cannabis research, clinical service delivery, or through their experience as a carer or service user, to participate in at least three rounds of interview via telephone/Skype/email. The research team compiles the outcome of reach round of interviews to inform a subsequent round until information saturation is reached. Results/Implications: When a consensus of information is achieved, the research team will develop an intervention manual based on the Delphi study findings to be utilized within a large scale RCT.

Conclusion: All types of substance use disorder increase the risk of death in people with schizophrenia, accounting for a potentially large proportion of the reduced life expectancy in this population. This highlights the importance of identifying and treating substance-related problems in this population.

The impact of substance use disorders on the risk of suicide and suicide attempts in people with a diagnosis of depression, bipolar disorder, personality disorder or psychoses Marie Louise Drivsholm Østergaard,1,2 Carsten Rygaard Hjorthøj,1,2 Annette Erlangsen,1,2 Merete Nordentoft1,2 1 Copenhagen University Hospital, Mental Health Center Copenhagen, 2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark

Introduction: Substance use disorders (SUDs) and mental illness increase the risk of suicide and suicide attempts. This risk is further increased among double diagnosis patients compared to people who suffer from either mental illness or SUDs. It is, however, unclear how the risk differs between people with different psychiatric diagnoses and different types of SUDs. In this study we investigate how SUDs affect the risk of fatal and non-fatal suicide attempts in four psychiatric populations. Methods: Data has been retrieved from several Danish registers and connected through encrypted personal identification numbers. Study subjects are all people born in Denmark since 1955 with a diagnosis of depression, bipolar disorder, personality disorder, and/or psychoses. They are included in one or more of the study populations according to diagnoses. Information on suicide attempts and SUDs is retrieved from somatic and psychiatric patient data. Furthermore, information on prescription medicine and municipal alcohol- and drug treatment programs is used to identify individuals with SUDs. Analysis: Data is analyzed in Cox regression. Study subjects are considered at risk when they get a diagnosis relevant to a specific psychiatric population, and until first suicide attempt – fatal or non-fatal – whichever comes first. Sociodemographic information and other relevant variables such as previous suicide attempts are taken into account in the analyses. Expectations: Through this study we hope to identify the subgroups of double diagnosis patients that are especially at risk of attempting suicide, and to get a deeper understanding of the interrelations of mental illness and SUDs.

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Symposium Session 12 Tuesday November 18, 1:00–2:25 p.m., Concord C Detection and treatment outcomes for people at ultrahigh risk of severe mental illness Chair: Mark van der Gaag, VU University/Parnassia Psychiatric Institute; speakers: Matthias Schwannauer, Helen Stain, Helga K Ising, Mark van der Gaag The detection of people at risk for developing psychosis has now been standardized in the use of the CAARMS or the SIPS, but the risk for developing bipolar disorder is still under development. The first presentation by Matthias Schwannauer is on the detection of people at risk for bipolar disorder and the efficacy of Interpersonal Therapy in the improvement of the core symptoms. The second presentation by Helen Stain is the sixth CBT study in the prevention of psychosis and conducted in Australia. It is a small sample and showed that attrition in the very young (mean age 16.3 years) is high. As a result, no differences were found with non-directive listening as a control therapy. In the third and fourth presentation, Helga Ising and Mark van der Gaag present recent follow-up data from the Dutch EDIE trial. This trial was capable of reducing the number of transitions to psychosis at 18-month follow-up. Helga Ising presents that the trial was also cost-effective; there was a health gain for lower costs and the UHR group can also be profiled into subgroups of lower and very high risk for a transition. The fourth presentation presents the 48-month outcomes. The risk reduction is largely preserved and the number of people in remission of subclinical psychotic symptoms is still significant. Overall, the detection of people at high risk is feasible and interventions are promising in postponing and the prevention of severe mental illness. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Early identification of bipolar disorder – two population studies Matthias Schwannauer,1 Helen Griffiths,2 Sonia Madrid1 1

University of Edinburgh, UK, 2NHS Lothian, UK

Bipolar disorder and associated mood instability is a highly compromising condition characterized by high relapse rates associated with significant social and economic costs. Early identification of vulnerabilities to mood instability is crucial, yet bipolar disorders remain notoriously hard to diagnose and treat and long delays between onset and appropriate recognition and treatment are common. Study 1 was conducted with 2500 participants of whom 400 were considered to be at high risk of developing bipolar disorder. Risk level was determined by means of the Hypomanic Personality Scale. The results suggest that interpersonal functioning is fundamentally different in high and low risk groups and its quality is strongly associated with hypomanic tendencies. In addition, they support the notion that developmental factors play a pivotal role in the manifestation of psychopathology, including bipolar disorder. They provide insight into what constitutes higher vulnerability to develop bipolar disorder, highlighting the importance of developmental aspects such as attachment, reflective functioning and emotion regulation as key components of early identification criteria. Study 2 describes the development and efficacy of IPT for adolescents at high risk for bipolar disorders. The results of this pragmatic RCT of CIT for adolescents at high risk of bipolar disorders indicate that IPT can be a highly effective treatment producing clear treatment effects on symptoms of mood related distress and relapse. The session will focus on the application of the CIT model to early bipolar disorder and examine the effects of treatment on core symptoms, coping styles and interpersonal problems.

Results: There were 57 youth randomized to either treatment or active control (N = 30: CBT; N = 27: NDRL), with the majority of participants female (60%) and an average age of 16.3 years. Attrition rates were high, with 40% and 53% of youth lost to follow-up at 6 months and 12 months respectively. At baseline and at 6 months the CBT group showed more distress associated with sub-clinical psychotic symptoms than the NDRL group. This effect disappeared at 12 months. No other group differences were found at either 6 or 12 months. Discussion: High attrition rates at the time of follow up assessments made analyses underpowered. We will discuss the rates of engagement in the intervention itself and the characteristics of our sample in order to inform future treatment trials with young people.

Cost-effectiveness of CBT to prevent first-episode psychosis in ultra-high risk and further options for profiling Helga K Ising,1 Filip Smit,2,3,4, Stephan Ruhrmann,5 Rianne MC Klaassen,6 Judith Rietdijk,1,2 Nicolien SP Savelberg,1,2 Nadine AFM Burger,1 Nynke Boonstra,7 Dorien Nieman,8 Lex Wunderink,7,9 Don H Linszen,8 Mark van der Gaag1,2 1

Parnassia Psychiatric Institute, The Hague, The Netherlands, 2VU University and EMGO Institute for Health and Care Research, Amsterdam, The Netherlands, 3Netherlands Institute of Mental Health and Addiction, Utrecht, The Netherlands, 4VU University Medical Center, Amsterdam, The Netherlands, 5University of Cologne, Cologne, Germany, 6Mental Health Organisation Rivierduinen, Leiden, The Netherlands, 7Friesland Mental Health Services, Leeuwarden, The Netherlands, 8Academic Medical Center, Amsterdam, The Netherlands, 9University Medical Center Groningen (UMCG), Groningen, The Netherlands Aims: The first aim was to determine the cost-effectiveness of CBT to prevent first-episode psychosis in ultra-high risk (UHR). The second aim was to develop an optimized prediction model of a first-episode psychosis, as with current UHR criteria only 20% have a psychotic outcome after 2 years.

DEPTh: randomized controlled trial of cognitive behavioral therapy for young people at ultra high risk for psychosis Helen Stain,1 Sandra Bucci,2 Sean Halperin,3 Richard Emsley,4 Ulrich Shall,3 Terry Lewin,3 Vaughan Carr,3 Kylie Crittenden,3 Vanessa Clark,3 Mike Startup3 1

School of Medicine, Durham University, UK, 2School of Psychological Sciences, University of Manchester, UK, 3Centre for Mental Health Studies, University of Newcastle, Callaghan, New South Wales, Australia, 4Center for Biostatistics, University of Manchester, UK

Background: This will be the first presentation of the treatment outcomes for the Australian DEPTh trial of cognitive behavioral therapy (CBT) for youth at ultra high risk (UHR) for psychosis. The DEPTh protocol is based on the EDIE model (Morrison et al., 2004, 2012), but employed an active control condition, Non-Directive Reflective Listening (NDRL). Method: This is a single blind RCT of CBT compared to NDRL plus standard care conducted at two sites (urban-Newcastle, rural-Orange) with a 6-month treatment phase (weekly sessions) and a 12-month follow-up from randomization in young people meeting UHR criteria. Assessments were conducted at baseline, 6 months and 12 months. Measurement domains included symptoms, substance use, functioning and quality of life. Intention-to-treat analysis was performed using regression models. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Methods: 196 help-seeking UHR patients participated in the Dutch EDIE study. All individuals were treated with routine care (RC) for non-psychotic disorders. The experimental group received adjuvant CBT to prevent psychosis. We report intervention, medical, and travel costs; costs arising from productivity losses, treatment response defined as psychosis-free survival and quality-adjusted life years gained. Furthermore, baseline data on symptomatology, and environmental and psychological factors were analyzed with Cox proportional hazard analyses. Results: In the cost-effectiveness analysis, the proportion of averted psychoses was significantly higher in the CBT condition. CBT was less costly than RC by US$ 844 per prevented psychosis. The Cox proportional hazard model included five predictors: observed blunted affect, subjective complaints of impaired motor function, beliefs about social marginalization, decline in social functioning, and distress associated with non-bizarre ideas. The resulting prognostic index stratified the general risk into 3 risk classes with significantly different survival curves. In the highest risk class, transition to psychosis emerged on average ≥8 months earlier than in the lowest risk class. Conclusions: Firstly, add-on CBT for individuals at UHR resulted in significant prevention of psychosis, for lower costs compared with RC. Secondly, predicting a first-episode psychosis in UHR seems improved using a five-factor prediction model.

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9th International Conference on Early Psychosis Four-year outcome of the Dutch EDIE Trial: the prevention of transition to psychosis in ultrahigh risk patients Mark van der Gaag,1,2 Helga K Ising,1 Nicolien SP Savelsberg,1,2 Nadine AFM Burger,1 Moniek Willebrands-Mendrik,3 Judith Rietdijk,1,2 Rianne MC Klaassen,4 Nynke Boonstra,5 Dorien Nieman,3 Sara Dragt,3 Don H Linszen,3 Lex Wunderink,5,6 1

Parnassia Psychiatric Institute, The Hague, The Netherlands, 2VU University and EMGO Institute for Health and Care Research, Amsterdam, The Netherlands, 3University of Amsterdam, Amsterdam, The Netherlands, 4Mental Health Organisation Rivierduinen, Leiden, The Netherlands, 5Friesland Mental Health Services, Leeuwarden, The Netherlands, 6University Medical Center Groningen, Groningen, The Netherlands Aims: To examine the 4-year outcome of the Dutch Edie trail in preventing and/or postponing a first psychotic episode in patients with an ultrahigh risk for developing psychosis. Methods: 196 help-seeking UHR patients participated in the Dutch EDIE study. 14 did not give consent for a follow-up measurement. Of the 182 patients 113 could be reassessed and in another 31 patient we could score the transition status. Outcomes examined were transition to psychosis, remission of subclinical psychotic symptoms, time to transition, social and occupational functioning, depression and social anxiety. Results: Only two patients in the experimental group made a transition to psychosis in the period between month 18 and 48. After 48 months, 12 had a transition in the experimental group and 22 in the control group. The difference was at tendency level of significance (p = .08). Remission of the subclinical symptoms was more prevalent in the experimental condition (77%) then in the control condition (58%; p = .03). Mean survival time was not significant (p = .09). Results on other outcome measures under still being analysed. Conclusions: CBT designed to prevent the transition to psychosis is effective at 18-month follow-up and showed a tendency at 48-month follow-up. The risk reduction at 18 months was 51% and at 48 months the risk reduction was 43%. For some patients, CBTuhr accomplished postponement of the transition to psychosis. The intervention was effective in reducing the subclinical symptoms at 18 and 48 months, which suggests a strong preventive effect.

Symposium Session 13 Tuesday November 18, 2:30–3:55 p.m., Concord A Long term outcome for first-episode psychosis – results from four large studies Chair: Carsten Hjorthøj, Mental Health Center Copenhagen; co-chair: Peter Jones, Cambridge University; speakers: Peter Jones, Carsten Hjorthøj, Ingrid Melle, Lex Wunderink Our knowledge of the long-term course and outcome of psychosis is limited both by the methodological heterogeneity of existing studies and by a paucity of epidemiologically robust studies of first-episode cohorts. In this symposium, we present the ten year follow-up of two large catchment area-based cohorts (the AESOP-study from UK, and the NorwegianDanish TIPS study and the 10-year follow-up of the Danish OPUS trial and the 7-year follow-up of discontinuation versus maintenance therapy trial from the Netherlands. We will especially focus on the proportion of patients who at long-term follow-up experience stable symptom remission and are not treated with antipsychotic medication.

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Ten-year outcomes of psychotic disorders: the ÆSOP-10 study Peter Jones,1 C Morgan,2,3 J Lappin,3,4 H Heslin,5 K Donoughue,6 B Lomas,7 U Reininghaus,2 A Onyejiaka,2 T Croudace,8 Robin Murray,3,4 P Fearon,9 P Dazzan3,4 1 Department of Psychiatry, University of Cambridge, UK, 2Centre for Epidemiology and Public Health, Health Service and Population Research Department, Institute of Psychiatry, King’s College London, UK, 3National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, UK, 4Department of Psychosis Studies, Institute of Psychiatry, King’s College London, UK, 5Centre for Economics of Mental and Physical Health, Health Service and Population Research Department, Institute of Psychiatry, King’s College London, UK, 6Addictions Department, Institute of Psychiatry, King’s College London, UK, 7Division of Psychiatry, University of Nottingham, UK, 8Department of Health Sciences, University of York, UK, 9Department of Psychiatry, Trinity College, Dublin, Ireland

Background: Schizophrenia was originally conceived as a deteriorating disorder but the broader group of psychotic illnesses may have a wide range of outcomes. Objective: To describe the 10-year outcome of a cohort with first-episode psychosis. Method: We followed-up at 10 years the ÆSOP cohort, 557 subjects with a first-episode of psychosis identified in two geographically defined areas of the UK during the late 1990s. Results: Thirty-nine (7.0%) cases had died, the majority through unnatural means. Thirty (5.4%) had emigrated, and eight (1%) were excluded; information on follow up was collated for 394 (82%) of the remaining 480. Most (270, 77%) experienced at least one period of remission but the majority (211, 71%) had been unemployed for more than 75% of the follow-up period. Overall, outcomes were worse for men and those with a nonaffective diagnosis. Conclusions: The overall symptomatic course of psychoses may be better than previously thought, but social outcomes in 21st century UK are disappointing.

Ten-year follow-up of the Opus trial for first-episode psychosis Carsten Hjorthøj,1 Gry Secher,1 Stephen Austin,1,2 Ole Mors,2 Merete Nordentoft1 1

Mental Health Services – Capital Region of Denmark, Mental Health Centre, 2Aarhus University Hospital, Research Unit, Department P, Denmark

Introduction: Long-term follow-ups of first-episode psychosis trial cohorts provide unique opportunities for examining course of illness and long-term treatment effects. Methods: 547 participants with a recent F2 diagnosis were recruited and randomized to either Opus early intervention or standard treatment for 2 years. The 10-year follow-up rate was 70% of those living in Denmark. Results: 368 were assessed at 10 years, with a recovery rate of 58 (15.8%). 61.3% had remission of psychotic symptoms, 47.0% had remission of negative symptoms, and 37.4% had remission of both. There were no differences between Opus and standard treatment on these measures (p = 0.53, p = 0.55, p = 0.14, and p = 0.35, respectively). 29 (5.3 %) participants had died, evenly distributed (p = 0.83). 29.7% had psychotic-symptom remission and did not receive antipsychotics; 29.7% had psychotic-symptom remission on antipsychotics; 9.9% had psychotic symptoms but were not medicated, and the remaining 30.7% had psychotic symptoms despite receiving antipsychotics (p = 0.48 between groups). There were no differences regarding symptom levels, use of psychiatric services, etc. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA The relation between antipsychotic medication history and ten-year outcome in first episode psychosis 1

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Ingrid Melle, Jan Olav Johannesen, Wenche ten Velden Hegelstad, Ulrik Haahr,3 Erik Simonsen,4 Jan Ivar Røssberg,5 Thomas McGlashan6 1

NORMENT Centre for Psychosis Research, University of Oslo, Norway, Stavanger University Hospital, Stavanger, Norway, 3Early Psychosis Intervention Center, Psychiatry Roskilde, Denmark, 4Department of Psychology and Educational Studies, University of Roskilde, Denmark, 5Division of Mental Health and Addiction, Oslo University Hospital, Norway, 6Yale School of Medicine, New Haven, Connecticut, USA

Symposium Session 14 Tuesday November 18, 2:30–3:55 p.m., Concord B

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Objective: Antipsychotic medication has significant clinical effect in reducing psychotic symptoms and preventing relapse in psychotic disorders. Many are however negative to long-term use due to side-effects and clinical experience indicates that some patients manage well without medication in the longer term. Methods: 281 patients with first-episode, schizophrenia spectrum disorders entered a medication algorithm advising 2 years continuous medication. Patients were followed from first week of treatment with re-evaluations after 3 months, 1, 2, 5 and 10 years. 174 (69% of those alive) participated in the 10-year follow-up. Results: At follow-up, 86 (49.5 %) were psychotic (13 (5%) continuously since baseline) while 46 (26.5%) were in symptomatic remission and 42 (24%) were recovered. There were no group differences in the number of patients using antipsychotics and in defined daily dosages (DDD) at baseline, 3 and 12 months follow-up, but a significant difference between the non-remitted and the recovered group in the number using antipsychotics and in DDD at the 2- and 10 year follow ups. A repe ated measures ANOVA indicated no time-effect on total DDD, but a time × group effect with significantly different patterns for the non-remitted and recovered groups.

Childhood trauma and risk for psychosis: mechanisms, interventions and outcomes Chair: Helen Stain, School of Medicine, Pharmacy and Health, Durham University; speakers: Helen J Stain, Helen L Fisher, Emmanuelle Peter, Sarah Bendall We currently know that childhood trauma and subclinical psychotic symptoms are pluripotent risk factors for developing major and severe mental illness. For example, the odds ratios following trauma are 4.4 for PTSD, 2.8 for drug abuse, 2.7 for depression, 2.4 for panic disorder, 1.9 for alcohol abuse, 1.9 for simple or social phobia, and 1.8 for generalised anxiety disorder (Teicher & Samson, 2013), with researchers reporting the average odds ratio for a psychotic disorder of 2.9 in a population cohort (Bebbington et al., 2004) and 2.8 in a meta-analysis of approximately 80,000 subjects (Varese et al., 2013). The development of psychopathology for those who have experienced childhood trauma occurs at a younger age, with more severe symptoms, more comorbid disorders, greater suicide risk and a reduced treatment response (Teicher & Samson, 2013). People with six or more adverse childhood experiences live about 20 years less than people without these events (Brown et al., 2009). Our symposium will discuss the potential mechanisms by which childhood trauma leads to mental health problems and the interventions to target these problems.

Conclusion: The recovered patients used lower doses of antipsychotics and were more likely to be unmedicated after 10 years than non-remitted patients, with the symptomatically remitted patients forming a middle group. Patterns of medication use started to diverge after 2 years in treatment and were not fully explained by symptomatic differences.

Long-term outcome following early dose-reduction of antipsychotics in remitted first episode psychosis

The relational model of childhood trauma and ultra high risk for psychosis

Lex Wunderink,1,2 RM Nieboer,1 FJ Nienhuis,2 S Sytema,2 D Wiersma2

Helen J Stain,1,2 Inge Joa,2,3 Wenche ten velden Hegelstad,2 Lauren Mawn,1 Olav Johannessen2,3

1 Department of Research and Education, Friesland Mental Health Services, Leeuwarden, The Netherlands, 2Department of Psychiatry, Rob Giel Research Center, University Medical Center Groningen, University of Groningen, The Netherlands

1 School of Medicine, Pharmacy & Health, Durham University, UK, 2TIPSRegional Centre for Clinical Research in Psychosis, Stavanger University Hospital, Norway, 3Faculty of Social Sciences; University of Stavanger, Norway

Objective: Comparing 7-year outcome of early antipsychotic dose-reduction/discontinuation (DR) with maintenance treatment (MT) on remission, relapse and recovery in remitted first episode psychosis (FEP).

Background: Trauma occurring in childhood coincides with the period for a child’s development of relational understanding such as attachment to others, and the reflective awareness of self and others (Holmes, 2002). Childhood trauma itself often involves attachment disruption and interpersonal violence in the context of primary relationships thus leading to difficulty with social functioning in adulthood. There is consistent evidence of high rates of trauma history for people with psychosis (Bentall et al., 2012; Varese et al., 2012). An adolescent population study showed the development and persistence of sub-threshold psychotic symptoms was associated with parental psychopathology and childhood trauma (Wigman et al., 2012).

Method: FEP patients (N = 128) symptomatically remitted for 6m during their first treatment year who completed an 18 months trial comparing MT and DR were followed-up at 7 years. Symptomatic remission criteria were adopted from Andreasen et al., functional remission criteria were based on a functioning scale. Recovery was defined as meeting both criteria sets. MT or DR strategy, and baseline parameters were entered in a logistic regression analysis with symptom and functional remission and recovery at 7-years follow-up as dependent variables. Results: 103 patients consented to participate. DR-patients showed twice the recovery-rate of MT-patients (40% against 18%), odds ratio 3.5 (P = .014). Symptomatic remission-rates were equal (69% and 67%). Better DR recovery-rates were attributable to higher functional remission-rates (46% vs. 20%) in DR. Predictors of recovery were DR, baseline living together and less severe negative symptoms. During the last 2 years of follow-up the mean daily dose in haloperidol equivalents was 2.20 mg in DR vs. 3.60 mg in MT (P = .031). Relapse-rates were initially higher in DR but leveled at 3 years; 61.5% relapsed in DR and 68.6% in MT in 7 years. Conclusion: DR of antipsychotics during early stages of remitted FEP significantly improved 7-years outcome in terms of recovery and functional remission compared to maintenance treatment. Though initially relapserates in GD were higher, these equaled those in MT from 3 years to the end of the study. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Method: The paper will present evidence from the literature in support of the impact of childhood trauma on relational capacity and style for young people at risk for psychosis. Data from the Norwegian TIPS program will illustrate the relational impact in adulthood for people with a first episode of psychosis. Discussion: The relational model provides a framework to understand the potential pathways into and out from the ultra high risk for psychosis status. It emphasizes the importance of reframing UHR as being UHR for a range of mental health problems as well as psychosis. Furthermore, the model shows there are clear implications for service delivery and choice of interventions. For example, childhood trauma has been associated with insecure attachment styles, which are associated with psychotic symptoms, difficulty with engaging in services, and more avoidant coping strategies (Gumley et al., 2013).

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9th International Conference on Early Psychosis The role of childhood abuse in the course and outcome of psychotic disorders over 10 years Helen L Fisher,1 Paola Dazzan,1 Julia Lappin,1 Margaret Heslin,1 Gillian Doody,2 Peter Jones,3 Robin M Murray,1 Craig Morgan1 1

Institute of Psychiatry, King’s College London, UK, 2University of Nottingham, UK, 3University of Cambridge, UK

Increasing evidence suggests that exposure to traumatic events in childhood is linked to the emergence of psychotic disorders in adulthood. However, the impact of childhood trauma on the longer-term outcomes of psychosis is largely unknown. Initial research suggests that early trauma is associated with worse clinical and functional outcomes amongst those with psychotic disorders. However, these studies suffer from a range of methodological limitations. Therefore, this presentation will explore the impact of childhood abuse on the course and outcomes of psychotic disorders over a 10-year period utilising comprehensive assessment tools in an epidemiological sample of 214 first-presentation psychosis patients. Data are drawn from the Aetiology and Ethnicity of Schizophrenia and Other Psychoses (AESOP) study of individuals from South London and Nottingham, UK, who presented to mental health services for the first time with psychosis between 1997 and 2000. Information on childhood abuse was obtained retrospectively using the Childhood Experience of Care and Abuse Questionnaire at baseline and extensive information on psychosis course and functional outcomes over the subsequent 10 years was obtained via face-to-face interview or clinical records. Psychosis cases who reported exposure to physical, sexual or emotional abuse prior to age 17 were more likely to achieve remission within 6 months of first presentation than non-exposed cases (OR = 2.91). However, they were at increased risk of self-harm (OR = 3.3) and suicide attempts (OR = 2.3), had more severe positive psychotic symptoms (OR = 3.2) and were less likely to be employed (OR = 0.4) during the 10-year follow-up period. The clinical implications of these findings will be discussed.

Cognitive pathway between trauma and psychosis Emmanuelle Peter,1 Monica Charalambides,1 Thomas Ward,1 Mike Jackson,2 Craig Morgan,1 Philippa Garety1 1 Institute of Psychiatry, King’s College London, London, UK, 2Bangor University, Bangor, UK

Cognitive models of psychosis suggest that (1) appraisals are key in determining the transition from benign anomalous experience to psychotic symptoms, and (2) trauma may be one of the predisposing factors to psychosis, which is increasingly supported by empirical evidence (Varese et al., 2012). However, it remains unclear whether trauma predisposes to the development of anomalous experiences, or to the pathogenic appraisals which transform them into psychotic symptoms. In a pilot study, the contribution of appraisals of anomalous experiences and trauma to the development of ‘need-for-care’ was investigated in two groups reporting equal levels of psychotic-like experiences with and without a need-forcare (Lovatt et al., 2010). The clinical group was more distressed, endorsed more externalising and personalising appraisals, and fewer psychological/ normalising appraisals of their experiences, than the non-clinical group. Contrary to expectations, both groups had equally high scores on the Trauma History Questionnaire (Green, 1996). However interpersonal trauma specifically was associated with more maladaptive, and fewer adaptive, appraisals. These results suggest that ‘need-for-care’ is characterised by distress and personalising appraisals, but not by a higher incidence of trauma. The role of interpersonal trauma, specifically, may be to predispose to a ‘paranoid’ world view, leading to maladaptive appraisals of anomalous experiences. Data from a larger sample (N = 150, from the UNIQUE study (Unusual Experiences Enquiry Study)), which investigated further the potential cognitive pathway between victimisation and psychosis using a more thorough assessment of interpersonal trauma and victimisation experiences, and appraisals of experimentally-induced anomalous experiences, will be reported and discussed

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TRIPP: TRauma-Informed Psychotherapy for Psychosis Sarah Bendall,1 Mario Alvarez-Jimenez,1 Craig McNeil,2 Shona Francey,2 Patrick D McGorry,1 Eoin Killackey,1 Henry J Jackson3 1

Orygen Youth Health Research Centre and Centre for Youth Mental Health, University of Melbourne, 2Orygen Youth Health Clinical Service, 3 School of Psychological Sciences, University of Melbourne, Melbourne, Australia Traumatic experiences, and their symptomatic and functional consequences, are becoming increasingly important in the treatment of first episode psychosis (FEP). Our recent data shows that post-traumatic stress disorder (PTSD) in FEP is common and results from both childhood trauma and acute psychosis (47% and 39% respectively). Thus far, trials of the treatment of trauma symptoms in psychosis have focussed on PTSD symptoms. However, other potential sequelae of trauma, such as dissociation have been found to be prevalent in those with trauma and psychosis, some of which have been implicated in the development of hallucinations and delusions. Further, these symptoms are often co-morbid with each other and, as such, treatment of several of these sequelae within one therapeutic intervention may be optimal. We have developed a traumainformed psychotherapy for psychosis (TRIPP). A trial of TRIPP is currently underway. TRIPP treatment involves two phases: the first of which comprises two concurrent modules: a safety/coping module that aims to build emotional coping resources for talking about trauma and an assessment module that leads to an individual formulation that involves developing an understanding of the relationship between traumas and current symptoms. The second phase includes several treatment modules (e.g., emotional exposure/disclosure; dialogue with voices, combating avoidance) that are conducted in a flexible manner. This trial is unique as it is targeting PTSD, dissociative and psychotic symptomatology; and it is a treatment being delivered within the current case management model of a public mental health treatment service, so requires no extra resource for implementation.

Symposium Session 15 Tuesday November 18, 2:30–3:55 p.m., Concord C Development and delivery of ARMS services around the world: implementation challenges and how to overcome them Chair: Kazunori Matsumoto, Tohoku University; co-chair: Masafumi Mizuno, Toho University; speakers: Kazunori Matsumoto, Rodrigo Bressan, Lucia Valmaggia, Swapna Verma The notion of ‘at-risk mental state’ (ARMS) has demonstrated already the value both to identifying individuals in a putative prodromal state for psychosis and for risk reduction using psychological and pharmacological interventions. However, the similar concept, ‘attenuated psychosis syndrome’ (APS), was finally included within the DSM-5 as a condition for further systematic study. The primary reservation about APS is that supportive evidence in this field has been established in academic and research settings in a limited countries so that several barriers exist to the implementation of the ARMS concept in real world settings. First, diagnostic reliability of ARMS has not been established in routine clinical settings. Therefore, there is a possibility of over- or under-diagnosis, which may prompt inappropriate interventions and ethical issues. Second, because most individuals with ARMS have relevant clinical needs in addition to the risk of conversion to psychosis, services for ARMS will need to meet those particular needs. Finally, we need to address the issue of generalizability of the ARMS concept to different cultural settings and healthcare systems around the world. Additional observations in various regions of the world, with an emphasis on a clinical perspective, are imperative for the generalizability of the ARMS concept. In this symposium, speakers from different parts of world will discuss specific problems they have in their local clinical settings and how to overcome challenges of applying the ARMS concept to real world settings. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Implementing at-risk mental state services in a Japanese clinical setting

Development and implementation of the London Early detection And Prevention (LEAP) service in an inner London prison setting

Kazunori Matsumoto,1,2 Noriyuki Ohmuro,2 Masahiro Katsura,2 Chika Obara,1 Tatsuro Kikuchi,1,2 Yumiko Hamaie,2,3 Emi Sunakawa,2 Fumiaki Ito,1,3 Miyakoshi Tetsuo,4 Hiroo Matsuoka1,2

Lucia Valmaggia,1,2 Manuela Jarrett,1,2 Catherine Campbell,1,2 Majella Byrne,1,2 Juliana Onwumere,1,2 Vyv Huddy,1,3 Tom Craig,1,2 Andrew Forrester1,2

1 Tohoku University Graduate School of Medicine, 2Tohoku University Hospital, 3Tohoku Pharmaceutical University Hospital, 4Chiba Prison, Japan

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Background: The concept of at-risk mental state (ARMS) is valuable for identifying individuals in a putative prodromal state of psychosis and for reducing conversion risk. However, since most evidence is derived from longitudinal observations in Western countries, observations from the rest of the world are imperative if the concept is to be generalized to various clinical settings.

In this talk, we describe the development and implementation of LEAP. LEAP is an innovative service providing early detection and early intervention for emerging mental health problems within a prison setting. The service offers tailored interventions to prisoners and their families with the objective of preventing the onset of severe mental health problems and family breakdown. Our work to date has demonstrated the feasibility of implementing early detection of psychosis within prison and, at the same time, has brought to light that prevention work in mental health should not be focused solely on the psychosis risk, but rather on the full range of potentially serious mental health disorders. A key finding of our earlier work is that, in addition to the 5% of prisoners identified with At Risk Mental State for psychosis, a further 11% were experiencing other emerging mental health problems. Currently, prison mental health services have no provision for these individuals until they develop more severe mental health problems. Furthermore, the link between prison and community services after release is often problematic and there is a need for ‘gatework’ in the weeks before release to help prisoners to prepare for their reintegration into the community. Central to this issue is the finding indicating that a chaotic and disrupted family and social support network can result in a range of problems, which contribute to coming back to prison. Importantly, family support can reduce the risk of inmates becoming socially isolated.

Methods: A naturalistic longitudinal study was conducted at a specialized early psychosis clinic at a university hospital in Sendai, Japan. Individuals with ARMS (n = 106) were recruited and followed on a case-by-case treatment basis. Results: Although the baseline characteristics of the participants generally replicated previous studies, no one had a history of substance use. Twothirds of the participants were psychiatrist referrals; 83 were followed for at least 1 year, with a mean follow-up of 2.4 years. One-third received antipsychotic medication during follow-up and 14 developed psychosis. The estimated cumulative transition rate was 11.1% at 12, 15.4% at 24, and 17.5% at 30 months. Compared to non-converters, converters showed more severe attenuated psychotic symptoms. Discussions: This study replicated previous major Western longitudinal studies, though risk factors associated with substance use appear much lower than in studies from Western countries. Although many patients with ARMS directly visit psychiatrists under universal health insurance coverage, overdiagnosis of schizophrenia and overprescription of antipsychotics are concerns. Improving education for psychiatrists and implementing an appropriate clinical service system is necessary in Japanese clinical settings to address this population’s needs.

King’s College London, Institute of Psychiatry, 2LEAP, South London and Maudsley NHS Trust, 3University College London, London, UK

Clinical Service for At-Risk Mental State – the Singapore experience Swapna Verma, Sujatha Rao, Lye Poon Institute of Mental Health, Singapore

Early intervention in psychosis: a map of Latin America clinical and research initiatives Rodrigo Bressan,1,2,3 Elisa Brietzke,1,2 Ary Neto,1,2,3 Álvaro Dias,2 Rodrigo Mansur1,2 1 Program of Recognition and Intervention in Individuals in At-Risk Mental State (PRISMA), Department of Psychiatry, Universidade Federal de São Paulo, 2Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo, 3Program of Schizophrenia (PROESQ), Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil

Objective: The presentation aims to review Latin America’s Early Intervention Services (EIS) in psychosis, and to shed light onto their challenges and particularities. Method: An Internet-based search comprising medical societies’ websites, published articles, and major universities’ websites was conducted and the results were critically discussed. Results: Latin American countries are profoundly deficient in specialized EIS. Our research found seven target services, among which four are based in urban areas of Brazil, inside tertiary hospitals or universities. Among the initiatives advanced by these centers, there are partnerships with the public educational system and other community-based efforts toward knowledge transfer. On the other hand, several challenges remain to be accomplished, especially in relation to their broadening and expansion, which is necessary to match the existing demand. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Introduction: The Support for Wellness Achievement Programme (SWAP) was established in in March 2008 within the remit of the Singapore Early Psychosis Intervention Programme to provide a comprehensive and integrated assessment and treatment service for those experiencing At Risk Mental States (ARMS). The management of these individuals is done within a multidisciplinary framework with focus on psychosocial interventions. Methods: From March 2008 to March 2014, 240 patients were accepted into the service. Socio demographic information was taken at baseline and all patients were evaluated using the Comprehensive Assessment of At Risk Mental State (CAARMS). Severity of psychopathology was assessed by Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and social and occupational functioning was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS) and Global Assessment of Functioning Scale (GAF). Results: The mean (SD) age of patients was 20.8 (3.4) years and 65.7% were males. The majority of patients (51.9%) belonged to the attenuated psychosis symptoms (APS) group. The mean (SD) total score at baseline for PANSS was 57.6 (7.9) and SOFAS was 53.06(9.9) indicating moderate impairment in social and occupational functioning. Of the 240 patients, 30 (12.5%) made the transition to psychosis within 2 years. Conclusion: Although the transition rates have been low and similar to other ARMS programmes internationally, it is crucial that individuals with ARMS who are help-seeking, distressed or disabled by their symptoms, have access to a service where assessment, monitoring and psychosocial interventions are offered.

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9th International Conference on Early Psychosis

Symposium Session 16 Tuesday November 18, 4:30–5:55 p.m., Concord A Enhancing Schizophrenia prevention and recovery through innovative treatments – a new network approach in Germany Chair: Peter Falkai, Ludwig-Maximilians-University Munich; co-chair: F. Markus Leweke, Central Institute of Mental Health; speakers: Stephan Ruhrmann, F. Markus Leweke, Peter Falkai, Wolfgang Woelwer Most recently, the ESPRIT network has been funded by the German Federal Ministry of Education and Research to introduce new interventions that will enhance schizophrenia prevention in high-risk subjects and recovery in the early post-acute phases of the illness, leading to relevant, measurable and economically valuable improvements in outcome in a 4 years perspective. This symposium aims to present the design, aims and program of this network approach. We will conduct joint translational projects to test innovative interventions to prevent conversion to schizophrenia in high-risk (HR) individuals, enhance recovery in schizophrenia patients in the early phases of the illness, and evaluate the outcome and efficacy of these interventions and implement them in clinical practice. For prevention of conversion in HR participants, we will conduct a randomized controlled trial (RCT) comparing two interventions with favorable risk-benefit ratios and clear translational rationale, a psychotherapy module aimed at improving social cognition, and a NMDA modulator/ antioxidant (N-Acetyl Cysteine). To enhance recovery in patients after an acute episode, three harmonized RCTs will test the following add-on treatments: cannabidiol, a mechanistically novel drug acting on the endocannabinoid system, actimetry-controlled physical exercise, and a psychotherapeutic intervention aiming at improving social cognition and social interaction. We will also test the hypothesis that transcranial direct current stimulation (tDCS) enhances the effects of cognitive training. We will evaluate treatment success for recovery, everyday function and stress reactivity, and quality of life. We provide cost-effectiveness analyses for experimental interventions and standardized inpatient treatment, and enhance transfer of successful results into practice.

Enhancing recovery in early schizophrenia – a controlled clinical trial investigating cannabidiol CR vs. placebo as an add-on to antipsychotic treatment F. Markus Leweke,1 Cathrin Rohleder,1 Peter Falkai,2 Andreas Heinz,3 Joachim Klosterkötter,4 Frank Schneider,5 Andreas Meyer-Lindenberg1 1 Central Institute of Mental Health, Mannheim, Germany, 2Ludwig-Maximilians-University Munich, Germany, 3Charité, Humboldt University Berlin, Germany, 4University of Cologne, Germany, 5RWTH Aachen, Germany

Current antipsychotic treatments of schizophrenia are only partially effective, and their use is often associated with serious side effects. Cannabidiol is a natural counterpart of the psychoactive component of marijuana, delta-9-tetrahydrocannabinol and has no psychotomimetic or addictive properties. In a controlled clinical trial of cannabidiol versus amisulpride in acute paranoid schizophrenia we showed a statistically significant clinical improvement in all symptoms clusters of schizophrenia compared to baseline with either treatment. Cannabidiol displayed a significantly superior side-effect profile in particular regarding prolactin elevation, extrapyramidal symptoms and weight gain. The favorable side-effect profile and potentially novel mechanism of action identify this molecule as a potential antipsychotic. However, long-term safety and efficacy data is still lacking. This study in 180 remitted schizophrenia patients is to evaluate the efficacy and safety of the novel compound cannabidiol in the maintenance treatment of schizophrenia in comparison to placebo as an add-on to an established treatment with either olanzapine or amisulpride, in a 12 months, double-blind, parallel-group, randomized, placebo-controlled clinical trial. Thereby, relevant data on cannabidiol’s antipsychotic potential will be gained.

Aerobic exercise for the improvement of cognition and enhancement of recovery in post-acute schizophrenia Peter Falkai,1 Andrea Schmitt,1 Alkomiet Hasan,1 Bernd Malchow,1 Frank Schneider,2 Henrik Walter,3 Wolfgang Woelwer,4 Andreas Meyer-Lindenberg5

N-Acetylcysteine (NAC) and integrated preventive psychological intervention (IPPI) in subjects clinically at high risk for psychosis Stephan Ruhrmann,1 Martin Hellmich,1 Rene Hurlemann,2 Wolfgang Maier,2 Joachim Klosterkötter1 1

University of Cologne, Germany, 2University of Bonn, Germany

Psychotic disorders are among the most expensive brain-related disorders in Europe. This is mainly due to their early onset and long-term disabling courses. Prevention is one of the key strategies to fight these deteriorating outcomes. Recent meta-analyses indicate promising preventive effects of both pharmacological and cognitive-behavioral interventions. Yet, reported transition rates are still too high. Clinical evidence suggests that disturbances of social functioning predict conversion to psychosis. Neurobiological evidence implicates glutamatergic dysfunction and redox imbalance in schizophrenia. We hypothesize that interventions targeting (i) social functioning and (ii) glutamatergic/oxidative pathways already in at-risk states would significantly reduce transition rates. To test these hypotheses, our study is designed as a randomized, placebo-controlled, 18-month trial (6 months of intervention plus 12 months of follow-up), involving 200 subjects at-risk for psychosis. Specifically, we will compare the preventive effects of a cognitive-behavioral and social-cognitive intervention to a pharmacological intervention with N-acetylcysteine, a drug with a pro-glutamatergic, neuroprotective and anti-inflammatory profile.

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1 Ludwig-Maximillians-University Munich, Germany, 2RWTH Aachen, Germany, 3Charité, Humboldt University Berlin, Germany, 4University of Duesseldorf, Germany, 5Central Institute of Mental Health, Mannheim, Germany

Schizophrenia is associated with poor psychosocial functioning in a substantial number of patients due to cognitive deficits primarily in memory domains like episodic and working memory connected to brain structural abnormalities like hippocampal volume decrease. We lately were able to show an improvement of episodic memory in chronic schizophrenia patients after 3-month training with bicycle ergometer accompanied by normalization of hippocampal volume (30 min 3×/week). In a subsequent second study, we detected a significant improvement in physical fitness, negative symptoms, episodic memory and executive function after 3 months of aerobic exercise (ergometer training 30 min 3×/week) with the main effects after 6 weeks. In the suggested study in 180 recent-onset schizophrenia patients, we plan to extend the exercise training period to 6 months and to stepwise increase the duration of training sessions up to 50 min (3×/week) to maximize the training intensity as suggested by the American College of Sport Medicine (ACSM) and investigate its long-term effects on cognition and psychopathological symptoms. A two-armed study is planned to investigate effects of aerobic exercise compared to a balance and tone program as control condition. Additionally, advanced imaging techniques for longitudinal analysis of structural and functional connectivity and volumetric brain changes will be applied in order to elucidate to what extent aerobic exercise can induce lasting plastic changes underlying functional recovery. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Efficacy of “Integrated Social Cognitive and Behavioral Skills Therapy (ISST)” in improving functional outcome in schizophrenia Wolfgang Woelwer,1 Wolfgang Gaebel,1 Wolfgang Maier,2 Joachim Klosterkötter,3 Andreas Fallgatter,4 Stefan Klingberg4 1

University of Duesseldorf, Germany, 2University of Bonn, Germany, 3University of Cologne, Germany, 4University of Tuebingen, Germany

Deficits in social functioning are a defining, very straining feature of schizophrenia precluding patients from participating in a satisfying life. Traditional drug and psychosocial therapy and available specific treatment strategies that directly target key determinants of functional outcome like neurocognition, social cognition, and social behavioral skills have produced only moderate effects leaving an urgent need for further optimization. The present trial aims to more efficaciously improve functional outcome by integrating social behavioral and social cognitive treatment strategies. Six months of “Integrated Social Cognitive and Behavioral Skills Therapy (ISST)” will be compared with “Neurocognitive Remediation Therapy (NCRT)” as active control condition within a randomized multicenter clinical trial using a two group pre-post design with 2 × 90 patients in the remitted early phase of schizophrenia. Beyond “all-causediscontinuation” as common primary outcome of all clinical trials of the ESPRIT-consortium, measures of functional outcome and subjective quality of life, patient experience as well as neurocognitive, social cognitive and social behavioral measures will be assessed at baseline (V0), after completion of treatment (V6), and after 6 months follow-up (V12). ISST is expected to reduce the 1-year discontinuation rate by 20% compared with NCRT, and to be superior in functional outcome measures by an effect size of at least d = 0.42.

Third talk will present Multiple Family Group intervention in the Early Psychosis Intervention Programme in Singapore. It is an activity-based and experiential programme which comprises four 2.5-hour weekly sessions. Fourth talk is about the Community Exercise Program (FitMind) in Hong Kong. FitMind was designed to promote exercise habit in the community consisting of a set of 10 aerobic movements. Participants were recruited to go through a 12-week aerobic exercise program.

Self-stigma in young people at high risk of psychosis Ziyan Xu Beijing Anding Hospital, Capital Medical University, China

Symposium Session 17 Tuesday November 18, 4:30–5:55 p.m., Concord B Healing the broken mind: Asian perspectives Chair: Young Chul Chung, Chonbuk National University Medical School; co-chair: Swapna Verma, Early Psychosis Intervention Programme, Institute of Mental Health, Singapore; speakers: Ziyan Xu, Young Chul Chung, Christopher Loh, Edwin HM Lee Individuals with early psychosis and their family members are often ashamed of being treated in mental health clinic. This embarrassment becomes a big obstacle deterring them from getting right treatment. This symposium will cover various treatment strategies from personal level to family and community levels in order to provide optimal intervention to individuals with early psychosis. First talk will address “Stigma issue” especially from Asian perspectives. The title of second talk is “From Threat to Rumination.” If one is being ignored or rejected, this leads to rumination and suspicion of others motives. The role of rumination in the development of paranoia will be presented. Also, key principles borrowed from Buddhism will be introduced as new approaches to dissolve rumination. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Early detection and intervention programs for young people at high risk for psychosis aim to increase help-seeking rates to improve clinical outcome. While it is likely that young people at risk of psychosis would encounter self-stigma about ‘mental illness’ label (Wright et al., 2011). The first onset of illness is often a catastrophic event for individuals and their family carers. Self-stigma may be particularly relevant for individuals who are experiencing their first diagnosis of a mental illness. Under the collectivistic nature of Chinese culture, people are more likely to internalize negative stereotypes of mental illness and suffer self-stigma. Fear of stigma has been identified as a significant barrier to help-seeking for health services. Self-stigma has been also associated with reduced hope, poorer well-being and reduced quality of life (Corrigan et al., 2013). Engulfment of self-stigma has been found to be particularly pertinent in individuals experiencing first episode of psychosis. (McCay et al., 2007). The risk of stigma may be particularly problematic because labeling or diagnosis typically be made with young adults who are in the early stage of development of their identify, formation of self-concept and entering into striving toward educational or vocational attainment (Yang et al., 2010). However, potential harmful effects of self-labeling and stigma are easy to be neglected in early intervention programs. Interventions are needed to facilitate a non-stigmatizing use of labeling in mental health services and society. Furthermore, effective strategies to address the self-stigma and its impact on young people at high risk of psychosis and in first-episode psychosis are also needed. The major elements of intervention are outlined as follows: (1) psychoeducation with realistic and empirical information about mental illness. In our experience, patients and carers prefer psychosocial to biogenetic explanations. (2) Motivational interviewing to change problematic behaviors, e.g. reluctant to seek help. (3) Reconstruction and normalization of self-stigmatized beliefs. (Needs to attention do not suggest stigma is flaw, which need to be corrected.) Focusing more on strengthening the art of acceptance to improve psychological flexibility. (4) Social skills training enhance specific skills: selective disclosure, openness and contact with others, and dealing with stigmatizing social situation, etc. (5) Personal empowerment and goal attainment to instill hope and develop realistic life goals. (6) Peer support to provide a range of services. In the Chinese community, caring for a person with a mental health problem is seen as a family responsibility. Therefore, family members are encouraged to participate in the sessions to provide emotional, instrumental and practical support, increase understanding and acceptance of the patients’ situation, refrain from treating them differently, and actively engage the young person at different levels to go back to normal life. Offering an early intervention in a positive frame and antistigma intervention program may represent a cost-effective way to reduce poor outcome for young people at high risk of psychosis and in firstepisode psychosis.

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9th International Conference on Early Psychosis From threat to rumination Young Chul Chung Department of Psychiatry Chonbuk National University Medical School, Jeonju, Korea The perception of threat is a central feature of paranoia. There is considerable evidence that paranoid individuals often experienced an abnormal frequency of adverse events such as bullying, discrimination and victimization. These precipitants may cause state of hyperarousal or induce anomalous perceptual experience. Combined with emotional distress, negative beliefs about the self, others and the world, and reasoning bias, hypervigilant individuals may try to make sense of internal unusual experience in negative and malicious way leading to the formation of threat belief. This threat anticipation cognitive model put forward by Freeman and Garety (2004) is supported by recent brain imaging studies that neural response of amygdale in response to fearful face or threat-related facial expressions has been found altered in patients with schizophrenia. However, there are different theoretical approaches to the understanding of delusion formation such as deficits in self-monitoring and ‘theory of mind’, externalizing attribution style or lower social rank. We would like to suggest rumination as another novel and crucial factor triggering and maintaining paranoid thinking. Nolen-Hoeksema (1987) developed the depressive rumination construct, defined as repetitive thought focused particularly on depressive feelings and symptoms. Rumination has been associated with elevated and prolonged sad mood, vulnerability to and maintenance of depression and metacognitive aspects of depression as well as negative health outcomes such as delayed recovery from coronary incidents. Recently, benefits of rumination-focused cognitive-behavioral therapy in persistent depression have been reported. With regard to psychosis, Halari et al. (2009) reported negative symptoms are associated with rumination. Patients’ family in China reported too much thinking as cause for schizophrenia. Freeman and Garety (1999) suggested that almost twothirds of individuals with persecutory delusions have a worry thinking style even about matters unrelated to paranoia which is, though, a little different concept from rumination. Cognitive slowing, one of the side effects caused by antipsychotic medication, could be a therapeutic benefit to subgroup of psychotic patients with high levels of rumination. We developed a new Rumination Scale (RS) consisting of three subdomains, frustration, anger, and foolishness, based on the teachings of Buddhism (three mind poisons). We recruited patients with anxiety disorder (n = 74), depression (n = 148) and psychosis (n = 65), and normal volunteer (n = 124) to compare psychological aspects using RS and other tools. The RS score in patients with psychosis was between the scores of patients with depression, and patients with anxiety disorder or normal volunteer though no significant differences between subgroups. Interestingly, there were significant positive correlations between the P3 (hallucinatory behavior) and P4 (excitement) of PANSS and total score of RS in patients with psychosis. These results may point to contributing role of rumination in the genesis of positive symptoms. Further studies are needed to explore relationships between rumination and paranoia and to refine the definition of rumination with regard to psychosis. Lastly, therapeutic implications for cognitive therapy will be discussed.

The development of a multiple family group programme for first-episode psychosis in Singapore Christopher Loh, Helen Lee, Justine Xue, Swapna Verma Early Psychosis Intervention Programme, Institute of Mental Health, Singapore Studies have suggested benefits of multiple family group (MFG) in improving families’ coping with first-episode psychosis. MFG in the Early Psychosis Intervention Programme (EPIP) in Singapore is a newly developed, activity-based and experiential programme, which comprises four 2.5hour weekly sessions. The MFG aims to (i) improve understanding of psychosis and its impact on the patients and their families, (ii) allow mutual learning, (iii) expand support network and reduce social isolation, and (iv) assist families to discover their strengths and resources. In the past year, the MFG has been conducted thrice. A total of eight families (27 participants) were involved in the MFGs. No family dropped out but some participants were unable to attend all the sessions. An evaluation form was developed to obtain feedback on the structure and content of the programme. The form comprises 19 four-point (“strongly disagree”, “disagree”, “agree” and “strongly agree”) Likert scale questions and three open-ended questions. Feedback from the open-ended questions revealed that the participants found the multi-family group setting, activities and discus-

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sion topics useful in supporting mutual learning and sharing. 25 out of 27 participants reported that they would recommend the MFG to other families in the same situation. 15 out of 19 Likert scale questions had more than 90% positive feedback from the participants. In conclusion, the MFG has generated positive feedback which suggests potential benefits for the families. Therefore, it would be worthwhile evaluating and shaping the MFG programme further to better meet the needs of families with firstepisode psychosis.

Community exercise program (FitMind) for patients with psychosis Edwin HM Lee, Christy LM Hui, WC Chang, Sherry KW Chan, Jessie JX Lin, Melody JQ Xu, LD de Sousa, Eric YH Chen Department of Psychiatry, The University of Hong Kong, Hong Kong Recent studies found exercise can improve cognition and symptom of patients with psychosis in addition to their physical health. However, most of the exercise interventions were gymnasium-based and it is difficult to generalize the benefits to the community in which many patients cannot access the facilities. FitMind is a community exercise program designed to promote exercise habit in the community through easy-to-learn aerobic exercise. It consists of a set of 10 aerobic movements, which could be linked up together to become interesting aerobic dance. Patients were recruited to go through a 12-week aerobic exercise program with volunteers to coach them to establish exercise habit. Volunteers did FitMind exercise with patients weekly and help to set goals of exercise habit each week, as well as reviewing patients’ progress. In additional to volunteers’ support, pamphlets, videos and website were also provided to facilitate development of exercise habit. The impact of the FitMind program will be discussed.

Symposium Session 18 Tuesday November 18, 4:30–5:55 p.m., Concord C Negative symptoms across the course of psychosis – implications for onset, treatment, and recovery Chair: Jo Hodgekins, University of East Anglia; co-chair: David Fowler, University of Sussex; speakers: Stephen Wood, Lucia Valmaggia, Jo Hodgekins, Mark van der Gaag Although much research has examined the negative symptoms of psychosis in samples of individuals with chronic schizophrenia, less is known about the presence, profile, and impact of negative symptoms in individuals at an earlier stage of psychosis. This symposium brings together research examining negative symptoms across the early course of psychosis, both before and after transition, and will consider implications for treatment and outcome. Lin & Wood will examine the presence of negative symptoms in an ultra high-risk sample and consider implications for transition to psychosis. Valmaggia will describe a latent class cluster analysis of individuals with at-risk mental state and consider the impact of both negative symptoms and impaired role functioning on outcome. Hodgekins will report findings from a latent class growth analysis examining the trajectory of negative symptoms in individuals with first-episode psychosis, including predictors of persistent negative symptoms and poor functional outcomes. Finally, van der Gaag will report findings from a meta-analysis examining the efficacy of psychological interventions for negative symptoms and discuss findings from a recent intervention trial for negative symptoms in individuals with first episode psychosis. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Negative symptoms in the at-risk mental state – association with transition to psychosis and functional outcome

Trajectories of negative symptoms following a first episode of psychosis and implications for social and functional recovery

Stephen Wood,1 Ashleigh Lin,1 Barnaby Nelson,2 Patrick McGorry,2 Alison Yung3

Jo Hodgekins,1 Brioney Gee,1 Max Birchwood,2 Max Marshall,3 Peter Jones,4 Swaran Singh,2 David Fowler5

1 University of Birmingham, UK, 2Orygen Youth Health, The University of Melbourne, Australia, 3University of Manchester, UK

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The at-risk mental state (ARMS) is generally defined by the presence of psychotic symptoms that do not meet the threshold for frank psychotic disorder, because they are attenuated in severity and/or duration. Furthermore, the transition to psychosis is determined on the basis of worsening in these same positive psychotic symptoms. The nature and course of negative symptoms in ARMS individuals is not commonly reported, and no study to date has examined the trajectory of this dimension. Here we present longitudinal data from 266 ARMS individuals (median duration of follow-up 6.6 years), testing the relevance of baseline negative symptoms for later outcome. We divided the ARMS group into those whose baseline negative symptoms (as assessed with the SANS) were above the 66th percentile (High NS, n = 87), and those at or below it (Low NS, n = 179). There was no difference in the proportion of each group that developed psychosis over the follow-up interval (31% vs 25%, p = 0.39), although more of the High NS group had a current or past diagnosis of schizophrenia (16% vs 6%, p = 0.02). The High NS group also had significantly lower functioning at follow-up (SOFAS; 64 vs 69, p = 0.01), and significantly lower quality of life (QLS; 90 vs 100, p = 0.01). These data indicate the relevance of negative symptoms at baseline for outcome. Though the impact on transition is low, high NS are associated with poor functioning and quality of life many years after initial assessment.

University of East Anglia, Norfolk, UK, 2University of Warwick, UK, 3University of Manchester, UK, 4University of Cambridge, UK, 5University of Sussex, UK Negative symptoms are not a stable trait but are subject to significant fluctuations over time. Individuals vary in the stability of their negative symptoms and those with persistently elevated negative symptoms are at highest risk of poor long term outcome. Research investigating individual trajectories of negative symptoms early in the course of non-affective psychosis is limited and little is understood about the longitudinal interplay of negative symptoms and social recovery. The aim of this study was to explore differing trajectories of negative symptoms using longitudinal data from a cohort of individuals receiving treatment for a first psychotic episode. Latent Class Growth Analysis (LCGA) was used to analyse change in negative symptoms and social functioning over a 12-month period using data from the National EDEN study. Persistent negative symptoms were present in a small group of individuals. However, poor social recovery outcomes were more common; suggesting that negative symptoms only partially explain delayed social recovery. Predictors of persistent negative symptoms were examined and implications for assessment and psychosocial interventions are discussed in the context of a current randomised controlled trial.

The battle for ameliorating negative symptoms has a restart Mark van der Gaag,1,2 Eva Velthorst,3 Filip Smit,1,4,5 Carin Meyer,3 Maarten Koeter,3,6 Anne-Kathrin Fett,3,7,8 Anton Staring,9 Lieuwe de Haan3 1

Negative psychotic symptoms and impaired role functioning in the at-risk mental state: a latent class cluster analysis study Lucia Valmaggia,1,2 Daniel Stahl,1 Yung Alison,3,4 Barnaby Nelson,4 Paolo Fusar-Poli,1,2 Patrick McGorry,4 Phillip McGuire1,2 1

Institute of Psychiatry, King’s College London, 2South London and Maudsley NHS Trust, London, UK, 3Orygen Youth Health, University of Melbourne, Australia, 4University of Manchester, UK Background: Individual symptom scores at baseline do not predict the course and outcome of the at risk mental state. Method: Latent class cluster analysis was applied to investigate data from 318 individuals with an at risk mental state for psychosis. The score on the Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to explore the number, size and symptom profiles of latent classes. Results: Latent class cluster analysis resulted in the following four classes: class 1 (mild) had the lowest scores on all the CAARMS items, they were younger, more likely to be students and had the highest Global Assessment of Functioning (GAF) score, 4.9% made transition to psychosis. Class 2 (moderate) scored moderately on all CAARMS items and was more likely to be in employment, 10.9% made a transition. Individuals in Class 3 (moderate–severe) scored moderately severe on the CAARMS and had a transition risk of 11.4%. Class 4 (severe) scored highest on the CAARMS, had the lowest GAF score, was more likely to be unemployed and had the highest transition risk (41.2%). Alogia, avolition/apathy, anhedonia, social isolation and impaired role functioning were the best items to distinguish between class 4 and the other classes. Conclusions: Negative symptoms and impaired social functioning at baseline are important for the outcome in the at risk mental state for psychosis. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Department of Clinical Psychology, EMGO Institute for Health and Care Research, VU University, Amsterdam, 2Parnassia Psychiatric Institute, The Hague, The Netherlands, 3Academic Medical Center, Department of Psychiatry, Amsterdam, 4Trimbos Institute (Netherlands Institute of Mental Health and Addiction), Utrecht, 5Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, 6Program for Mood Disorders, Academic Medical Center, Universiteit van Amsterdam, 7Department of Educational Neuroscience, Faculty of Psychology and Education, VU University of Amsterdam, 8Department of Psychosis Studies, Institute of Psychiatry, King’s College London, UK, 9 Altrecht Psychiatric Institute, The Netherlands Background: Most studies on CBT trials primarily focused on positive symptoms and investigated negative sympts only as secondary outcome. To enhance our understanding about factors contributing to improvement of negative symptoms, we reviewed all available evidence on these outcomes. Methods: A systematic search of the literature was conducted in PsychInfo and PubMed to identify RCTs reporting on CBT intervention’s impact on negative symptoms in schizophrenia. Random effects meta-analyses were performed on end-of-treatment, short-term and long-term change in negative symptoms. Results: Thirty-five publications covering 30 trials in 2312 patients, published between 1967 and 2013, were included. Our results showed that the studies’ pooled effect on symptom alleviation is small (Hedges’ g = .093 (CI 95% = −.028 − .214, p = 0.130)) and heterogeneous (Q = 73.067, df = 29, p < .001; ??2 = .081; I2 = 60.31) in studies with negative symptoms as secondary outcome. Similar results apply for studies specifically focused on negative symptom reduction (Hedges’ g = .157 (CI 95% = −.010 − .409, p = .225)) Meta-regression showed that stronger treatment effects were associated with an earlier year of publication, lower study quality and with CBT provided individually (as compared to group-based). Conclusions: The beneficial effect of CBT on negative symptoms found in older studies was not supported by more recent findings. These vanishing effects could not be explained by study or sample characteristics. Only individual therapies and on a tendency level more behavioral studies did somewhat better. Another promising avenue is a focus on asocial beliefs. A new trial targeting underestimation of hedonic, social and cognitive capacities in psychotic patients has just started.

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9th International Conference on Early Psychosis

Symposium Session 19 Wednesday, November 19, 12:45–2:10 p.m., Concord A Neurodevelopmental trajectories and psychiatric disorders Chair: Michio Suzuki, University of Toyama; co-chair: Christos Pantelis, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health; speakers: Matcheri S Keshavan, René S Kahn, Tsutomu Takahashi, Christos Pantelis Neuroimaging research has proven that structural and functional brain changes predate the onset of psychotic disorders such as schizophrenia. Some of those changes may be consequences of abnormal neurodevelopment during gestation, whereas dynamic brain changes after birth are also suggested to be involved in the increasing risk for developing psychosis. In particular, abnormalities in brain maturational process during adolescence, a period of remarkable physical, cognitive, and behavioral changes, have been the subject of investigations since incidence of many psychiatric disorders increases during adolescence. Abnormal brain maturation has also been implicated in progressive brain changes reported in schizophrenia patients after psychosis onset. Determining the neurodevelopmental trajectories of human brain structure and function and their aberrations in psychiatric disorders could contribute to improved understanding of the mechanisms underlying their complex clinical manifestations as well as development of a biological marker that might be useful for early intervention and prevention. This symposium highlights updated observations in psychopathological, cognitive, and neuroimaging studies in individuals at genetic high risk, those at clinical high risk, and patients with schizophrenia in early phases to better understand risk as well as resilience factors for emerging mental illness.

Cognitive change is related to brain loss in the early phases of schizophrenia René S Kahn, Manabu Kubota, Neeltje E van Haren, Wiepke Cahn University Medical Center Utrecht, The Netherlands Background: There is consistent evidence for cognitive changes prior to the onset of psychosis in schizophrenia. Also, progressive brain changes during the course of the disease have consistently been shown, but it has not been studied whether the two phenomena are related. Method: A total of 78 first-episode schizophrenia patients and 113 agematched healthy controls were tested twice with a 3-year interval. IQ and 1.5T sMRI were obtained at both time points. Surface-based analysis with FreeSurfer software (5.1.0) was applied to measure global and local cortical thickness change in each subject. yearly cortical thickness change was defined as the percent thickness change per year during the scan interval. Results: Cortical thickness, but not surface, decreased in the patients versus controls and this loss was significantly associated with decreases in IQ (r = .385, p = 0.015). This finding was particularly pronounced in the earliest phases of the illness (r = .588, p < 0.001) and was not confounded by medication use. Conclusion: Cortical thinning in schizophrenia is related to worsening in global cognitive function and that this is most prominent in the early stages of the illness. Whether this relationship can also be found in highrisk subjects needs to be studied.

Developmental trajectories and psychopathology in young relatives at risk for schizophrenia Matcheri S Keshavan,1,2 Jai L Shah,1,3 Neeraj Tandon,1 Debra M Montrose2 1

Harvard Medical School/Beth Israel Deaconess Medical Center, 2University of Pittsburgh Medical Center, 3Yale University School of Medicine, USA

Objectives: A great deal of research has focused on identifying predictors and developing early interventions for individuals with psychotic disorders such as schizophrenia. While the relationships between early psychopathology, neurocognitive and social deficits and later emergence of psychosis have been studied for some time, the temporal evolution of psychopathology and its neurodevelopmental parallels in individuals at high risk (HR) for schizophrenia is less well characterized. Method: Using age-appropriate structured diagnostic interviews and consensus diagnostic evaluations, we prospectively examined the ages of onset of axis-I psychiatric disorders in 169 adolescents and young adults (mean ∼15.9) at high familial risk for schizophrenia or schizoaffective disorder. Psychopathological, neurocognitive and neuroimaging assessments were carried out annually in a subset of these individuals and a group of age and sex matched healthy controls (HC) up to 3 years. Results: About 60% of HR subjects had one or other axis I psychopathology as evaluated longitudinally. Attention deficit/Conduct/Learning disorders had the earliest ages of onset, followed by Affective and Anxiety disorders and Substance use disorders. Sub-threshold (prodromal) syndromes and schizophrenia or related psychoses appeared latest, (initially Intermittent and later Chronic). The neurocognitive and neurobiological correlates of this psychopathological trajectory will be presented. Discussion: We propose that the premorbid and prodromal phases of schizophrenia in at-risk relatives may be characterized by “A_CLAASSic” trajectory of psychopathology emerging from childhood to young adulthood. Understanding such patterns of psychopathological evolution and their dynamic neurodevelopmental underpinnings could be of considerable importance for early detection and intervention efforts.

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Brain morphologic changes during the course of schizophrenia Tsutomu Takahashi, Michio Suzuki University of Toyama, Japan Previous MRI studies have demonstrated gross brain morphologic changes, such as altered sulcogyral pattern, at the onset of first-episode schizophrenia, suggesting an early neurodevelopmental disturbance. Recent studies in individuals at ultra high-risk of psychosis (UHR) further supported the neurodevelopmental pathology of schizophrenia. On the other hand, longitudinal MRI studies have demonstrated active progressive brain changes especially in temporal regions during the initial stage of illness, which may represent a pathological process in late neurodevelopment. In this study, we aimed to summarize our MRI findings in the early course of schizophrenia, including those in UHR individuals recruited from the Consultation Support Service in Toyama (CAST). The UHR subjects and schizophrenia patients exhibited a shallower olfactory sulcus depth and smaller adhesio interthalamica as compared with healthy controls, suggesting that abnormalities in these potential neurodevelopmental markers predate the onset of psychosis. The UHR subjects also shared an increased pituitary volume with first-episode schizophrenia, possibly reflecting a common vulnerability to stress in early psychosis. In longitudinal comparisons, the schizophrenia patients showed significant gray matter reduction of the superior temporal gyrus during firstepisode of psychosis, which was correlated with the severity of positive psychotic symptoms. They also showed mild volume reduction over time in the prefrontal cortex. These findings may support the role of both early and late neurodevelopmental processes as well as environmental factors such as stress in the development of psychosis. Further work in a larger UHR sample is required to examine the possible relation between the brain morphology and emergence of psychosis. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Trajectories of brain change during development: understanding risk and resilience factors for emerging mental illness Christos Pantelis,1 Stephen Wood,2 Vanessa Cropley,3 Patrick McGorry,4 Nitin Gogtay5 1

Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Australia, 2University of Birmingham, UK, 3Swinburne University of Technology, Victoria, Australia, 4Orygen Research Centre, The University of Melbourne, Melbourne, Australia, 5National Institute of Mental Health, Singapore Mental disorders like schizophrenia, mood disorders and substance abuse begin in adolescence and early adulthood. This is a time of active brain changes as adolescents mature into adulthood. Such maturational changes provide the context for understanding how and why these disorders arise during this critical period of development. I will first summarise the findings from the Melbourne early psychosis and prodromal studies examining premorbid and progressive brain changes during and following the onset of psychosis. I will consider whether the evidence supports these as risk-related markers of illness onset and transition. I will also examine evidence from studies of childhood schizophrenia (Gogtay et al., 2011). The findings suggest that biomarkers should be examined longitudinally to assess normal and abnormal trajectories during maturation and with the emergence of mental disorders (Pantelis et al., 2005; 2009). These trajectories include evidence for (a) neurodevelopmental lag, (b) neurodevelopmental arrest, and (c) neuroprogressive changes. These trajectories can also be considered to reflect the impact of both risk and resilience factors. Finally, I will consider the importance of examining trajectories of acute relapse and remission (Cropley et al., 2013, 2014).

Symposium Session 20 Wednesday, November 19, 12:45–2:10 p.m., Concord B

Psychopathological antecedents to severe mental illness in offspring of parents with major depressive disorder, bipolar disorder or schizophrenia Rudolf Uher, Jill Cumby, Lynn McKenzie, Jessica Morash, Alexa Bagnell, Lukas Propper, Sabina Abidi, Barbara Pavlova, Martin Alda Dalhousie University, Canada Although the familial risk for mood and psychotic disorders overlaps, antecedents to psychotic disorders (attenuated psychotic symptoms and basic symptoms) have not been explored in youth at familial risk for mood disorders. In the “Families Overcoming Risk and Building Opportunities for Well-being” (FORBOW) study, we assess psychopathological antecedents in offspring of parents with mood disorders and schizophrenia. At the time of writing, 108 high-risk offspring aged between 3 and 21 years (mean age 11) have been recruited and assessed with the Structured Interview for Psychosis-Risk Syndromes (SIPS) for ultra-high risk criteria and with the Schizophrenia Proneness Instrument, Adult (SPI-A) and Child and Youth version (SPI-CY), for the basic symptom criteria COPER and COGDIS. Sixteen (16%) offspring experienced one or more (attenuated) psychotic symptoms and 17 (17%) reported basic symptoms fulfilling the COGDIS or COPER high-risk criteria. The rate of basic symptoms and attenuated psychotic symptoms was elevated in the offspring of parents with both mood and psychotic disorders: psychotic symptoms or high-risk basic symptom profiles were present in 40% of offspring of parents with schizophrenia, 27% of offspring of parents with bipolar disorder and 29% of offspring of parents with major depressive disorder, compared to 0% in offspring of control parents. These preliminary data suggest that putative antecedents to psychosis, including high-risk basic symptom profiles and attenuated psychotic symptoms are common among offspring of parents with both psychotic and major mood disorders.

Prevalence of psychosis-risk criteria and symptoms in an inpatient sample of children and adolescents Frauke Schultze-Lutter,1 Chantal Michel,1 Petra Walger,2 Maurizia Franscini,2 Benno G. Schimmelmann1

Prevalence and significance of psychosis-risk criteria and symptoms outside specialized early detection services Chair: Frauke Schultze-Lutter, University of Bern; speakers: Rudolf Uher, Frauke Schultze-Lutter, Stephan Ruhrmann, Martina Brandizzi In clinical samples recruited in specialized early detection and intervention services, both ultra-high risk (UHR) and basic symptom criteria, are not only associated with a 1-year conversion rate of roughly 20% but also with various other impairments. Therefore, a UHR-related syndrome, the attenuated psychosis syndrome, was introduced as a condition for further studies in DSM-5 as a self-contained but not a risk syndrome. This preliminary placement was not least due to the fact that knowledge on the prevalence of attenuated psychotic symptoms – and other risk symptoms – in adolescent and adult clinical populations and in the general community is still lacking. The studies presented in the symposium address this important issue on new data of four different samples: (1) a 3–21-yearold sample at genetic high-risk for either psychosis or severe affective disorder, (2) an unselected 12–18-year-old sample of help-seeking youths routinely screened at child and adolescent out-patient services across Rome, (3) an 8–17-year-old inpatient sample not suspected to develop psychosis, and (4) a sample of 8–40-year-olds randomly selected from the general community. Consistently, UHR criteria were assessed with the Structured Interview for Psychosis-Risk Syndromes (SIPS) and basic symptom criteria with the Schizophrenia Proneness Instrument, Adult (SPI-A) and Child and Youth version (SPI-CY), respectively, in all four studies. Study results, and their comparison will shed light on the prevalence of risk criteria and symptoms and the context in which these might occur. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

1 University of Bern, Bern, Germany, 2University of Cologne, Cologne, Germany, 3University of Zurich, Zurich, Switzerland

Adolescents from the community have increased prevalence rates of attenuated psychotic symptoms (APS) and positive symptoms, with higher rates reported for children. APS were related to a higher psychiatric morbidity. Thus, APS and other risk criteria might be even more frequent in clinical child and adolescent samples, even if the clinical picture does not suggest the possible development of psychosis. We studied their prevalence and possible clinical impact in an inpatient sample of 8–17-yearolds (at the time of writing: N = 41). Ultra-high risk (UHR) and basic symptom (BS) criteria were assessed with the ‘Structured Interview for Psychosis-Risk Syndromes’ and the ‘Schizophrenia Proneness Instrument, Child and Youth version’. Only one patient (2%) met APS-related risk criteria. Additional 15 patients (37%) acknowledged at least any one past or present risk symptom (47% APS and 73% BS). Perception-related phenomena were most frequent: in 46% of those with BS, and in all with APS. The presence of risk symptoms was associated with significantly lower psychosocial functioning and a deficit in processing speed with no additional effect of age or gender. As expected, risk symptoms – especially perception-related – were frequent in children and adolescents with severe mental disorders requiring inpatient treatment. Yet, risk criteria were rarely met. Nevertheless, already the presence of risk symptoms was related to increased deficits in psychosocial functioning and processing speed, a potential core cognitive deficit in psychosis. This indicates that risk symptoms might have additional psychopathological significance in clinical inpatients that add to the impairments caused by their prominent disorder.

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9th International Conference on Early Psychosis Prevalence of at-risk criteria of psychosis in children and adolescents, and in young adults: results from two Swiss community samples Stephan Ruhrmann,1 Benno G. Schimmelmann,2 Chantal Michel,2 Alexandra Martz-Irngartinger,2 Caroline Linder,2 Frauke Schultze-Lutter2

Symposium Session 21 Wednesday, November 19, 12:45–2:10 p.m., Concord C

1

University of Cologne, Cologne, 2University of Bern, Bern, Germany

The prevalence and significance of APS and other risk symptoms in the general population, when assessed in the same way as in help-seeking persons, is still rather unclear. In two complimentary studies, we studied the prevalence of ultra-high risk and basic symptom criteria and symptoms assessed with the ‘Structured Interview for Psychosis-Risk Syndromes’ (SIPS) and the ‘Schizophrenia Proneness Instrument, Adult/Child and Youth version’ (SPI-A/SPI-CY) by trained psychologists in random community samples of age 8–17 and 16–40 years. At the time of writing, 1229 interviews with young adults and 55 with children/adolescents were completed. While only 2.8% of the young adults acknowledged the presence of any risk criterion, 9.1% of the children/adolescents did so. An even more pronounced age-related difference was found in the prevalence of lifetime risk phenomena: 25.2% of the young adults and 45.5% of the children/adolescents reported at least any one. Thereby, “perceptual abnormalities/hallucinations” of the SIPS, mainly on APS level, were most frequent in both samples. While risk phenomena occurred, at least temporarily, in a quarter of young adults and even in nearly half of the children and adolescents, only a minority fulfilled the frequency and onset requirements of SIPS and SPI-A/SPI-CY – again with higher rates in children and adolescents. This highlights the importance of these additional requirements of the risk criteria, but also the need to further examine developmental peculiarities. These factors might play a crucial role in the differentiation between ill and non-ill persons and thus should be studied in more detail.

It’s about time: improving physical health in FEP. Rationale for the HeAL approach Chair: Jackie Curtis, University of New South Wales; co-chair: Fiona Gaughran, Institute of Psychiatry, King’s College London; speakers: Debra L Foley, Christoph U Correll, Helene Speyer, Fiona Gaughran Many people experiencing psychosis face a future restricted not only by mental illness but also by poor physical health. Despite recent advances in our understanding the nature of psychosis and its treatments, those affected still lose up to 15–20 years of life. Higher rates of obesity, cardiovascular disease and diabetes contribute to a widening health gap and these physical health co-morbidities are now the most frequent cause of premature death for people with psychosis, being more common than suicide. This symposium will highlight the current evidence for emergent cardiometabolic risk in the early stages of treatment for psychosis drawing from large data sets from Australia, USA, Denmark and the UK. Weight gain and cardiometabolic disturbance are evident soon after antipsychotic treatment initiation in those experiencing first episode psychosis, compounded by high rates of tobacco use, inactivity and poor nutrition. In an effort to address these issues, the Healthy Active Lives (HeAL) declaration (www.iphys.org.au) argues that it is time to discard the traditional Cartesian dualism in favour of a far more holistic body and mind approach, right from the onset of psychosis. Routine antipsychotic adverse effect monitoring along with smoking cessation and lifestyle interventions should form part of routine multi-disciplinary care for first episode psychosis.

Liberiamo il Futuro: first results of an Italian early detection project Martina Brandizzi,1 A Masillo,1 M Curto,1 J Fortes Lindau,1 Georgio Kotzalidis,1 Eva Gebhardt,1 L Godeas,2 Diana Di Pietro,2 Paolo Girardi,1 Paolo Fiori Nastro1 1

Sapienza University of Rome, 2Community Mental Health Service of ASL Rome H, Rome, Italy

Best buys for early intervention to improve cardiometabolic health in adults with psychosis: an Australian perspective

Psychotic-like experiences (PLEs) are commonly endorsed in questionnaires in community and clinical populations, especially by adolescents. Within the early detection project “Liberiamo il Futuro” (LIF), the prevalence of attenuated psychotic-like experiences (APLEs) in a sample of help-seeking adolescents (11–18 years) and the correlation with age, functioning and risk status is explored. LIF aims to identify subjects at high risk for developing a psychosis according to the ultra-high risk (UHR) and the basic symptoms criteria among help-seeking adolescents (11–18 years) and young adults (18–30 years). To identify patients with an increased risk of psychosis, the Prodromal Questionnaire (PQ-92) was administered. Patients endorsing 18 or more APLEs on its positive symptoms subscale were further assessed with the Structured Interview for Psychosis-Risk Syndromes and the Schizophrenia Proneness Instrument, Child and Youth version. At the time of writing, 171 11–18-year-olds were assessed. Ninetyeight (41%) passed the PQ-threshold, and 82 were further interviewed. With great overlap between the symptoms, 20 adolescents (24%) reported UHR symptoms, 44 (54%) cognitive-perceptive basic symptoms (COPER) and 30 (37%) cognitive disturbances (COGDIS). APLEs are common in adolescents seeking help for mental problems. Since APLEs might index a risk for a much wider range of psychopathology than psychotic disorders only, more research is needed to understand when APLEs signal an incipient psychotic illness and which features are associated with a worse outcome. To this aim, basic symptoms may help to distinguish young people at risk for developing a psychotic disorder from those at risk for other psychopathological disturbances.

Debra L Foley,1 Andrew Mackinnon,1 Vera Morgan,2 Gerald Watts,2 Jonathan Shaw,3 Dianna Magliano,3 David Castle,1 John McGrath,4 Anna Waterreus,2 Cherrie Galletly5

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1 University of Melbourne, 2University of Western Australia, 3Baker IDI Heart and Diabetes Institute, 4University of Queensland, 5University of Adelaide, Australia

Those with psychosis are more likely to develop diabetes and to die prematurely from coronary heart disease than those in the general community. There is a pressing need to implement effective interventions that target the earliest expressions of cardiometabolic risk. The first aim of this work is to present data collected by the Australian National Survey of Psychosis (n = 1,155) to describe the prevalence of screened type 2 diabetes by age and gender, the prevalence of risk factors established in the general population, their association with type 2 diabetes in adults with psychosis, and to test if they confound the association between type 2 diabetes and treatment with the drugs clozapine or olanzapine. The second aim of this work is to present data collected by the Australian National Survey of Psychosis (n = 1,155–1,642) and The Australian Diabetes, Obesity and Lifestyle Study (n = 8,866), a general population sample, to describe which cardiometabolic risk indicators first distinguished those with psychosis from the general population, whether obesity explained the pattern of observed differences, and what the “best buys” for early intervention to improve cardiometabolic health in men and women with psychosis are based on this data. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Cardiometabolic risk in first episode schizophrenia-spectrum disorder patients: baseline results from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study Christoph U Correll The Zucker Hillside Hospital, Glen Oaks, New York Background: Schizophrenia individuals have high cardiovascular morbidity and mortality yet, risk status and moderators/mediators in the earliest illness stages are less clear. Methods: Baseline results of the NIMH-funded Recovery After an Initial Schizophrenia Episode (RAISE) study, collected at 34 sites in 21 US states from 07/2010 to 07/2012. Participants were patients aged 15–40 years with research-confirmed diagnoses of first-episode psychosis and 30 kg/m2) at baseline, and 35% at 1 year. Rates of central obesity were high, rising over the year from 45% to 56% exceeding the International Diabetes Federation threshold for metabolic syndrome. HbA1c levels rose over the first year (p = 0.001) with black patients having higher HbA1c levels at 12 months than white patients (p = 0.013). 17% had metabolic syndrome at baseline, rising to 25% at 12 months. 76% were tobacco smokers, smoking 10.7 cigarettes a day, with little change over the year. 53% were current cannabis users on presentation, with 42% using at 1 year. 22% had alcohol dependence at baseline, dropping to 10% at 12 months. 32% had low and 68% had moderate-high levels of physical activity at baseline with little change over the year. This large UK first episode study of cardiovascular risk in early psychosis shows significant rises in obesity, central obesity and HbA1c in the first year in this ethnically diverse patient group.

Conclusions: Psychiatric illness seems to affect body composition adversely, but antipsychotic treatment, especially with olanzapine, followed by quetiapine, even of short duration has noticeable adverse metabolic effects. Prevention of/early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring and smoking cessation interventions are needed from the earliest phases of treatment.

Associations between diet, sedentary behavior, cardiovascular fitness, and 10 years risk of cardiovascular disease in patients with schizophrenia Helene Speyer,1,2 Jesper Krogh,1,2 Merete Nordentoft1,2 1

Mental Health Center Copenhagen, 2University of Copenhagen, Denmark

Background: Patients with schizophrenia have a 20 years reduction in life expectancy, mainly due to cardiovascular disease (CVD). Aim: To investigate possible associations between diet, sedentary behavior, cardiovascular fitness, and 10 years risk of CVD in patients with schizophrenia. Method: Dietary and sedentary behavior were assessed in patients with schizophrenia and waist circumference above 102 cm (male) and 88 cm (female). We used a food frequency questionnaire and physical activity scale. Cardiovascular fitness (ml/kg/min) was assessed by an incremental bicycle test and 10 years risk of CVD was estimated with PRECARD. Results: 429 patients were included. Mean age was 38.6 (SD 12.4), and 54.1% were females. 10 years risk of CVD was 16.1% (SD 10.0) for males and 6.7% (SD 7.0) for females. According to dietary habits, 21.3% were classified as unhealthy, 60.7% as medium healthy, and 18.0% as unhealthy. Mean hours of sedentary behaviour were 10.1 (SD 3.7). There was no significant association between diet and sedentary behaviour with CVD risk. Mean cardiovascular fitness was 16.0 (SD 11.5) and the association with CVD-risk was −0.09 (95% CI. −0.17 to −0.02; p = 0.01). Analysis was adjusted for age and gender. Conclusion: We found no association between diet and sedentary behaviour with CVD risk. Cardiovascular fitness was significantly associated to CVD risk. These findings highlight the importance of physical activity, which could be an important target for CVD risk reduction in patients with schizophrenia. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Symposium Session 22 Wednesday, November 19, 2:15–3:40 p.m., Concord A Who shifted the goalposts? Psychosis and borderline personality disorder Chair: Andrew Chanen, The University of Melbourne, Orygen Youth Health Research Centre; Speakers: Andrew Thompson, Martina Jovev, Andrew Chanen, Félix-Antoine Bérubé Both psychotic disorders and borderline personality disorder have their onset in youth. Psychotic symptoms appear to be common among patients with borderline personality disorder and vice versa. Their cooccurrence is clinically well recognised, is associated with significant risks and is complex to treat. The separation of psychotic symptoms into ‘true’ and ‘quasi’ is clinically and scientifically problematic. Yet, there is currently no consensus regarding the authenticity, phenomenology, severity or treatment of these experiences. Evidence is accumulating for separate dimensional models of psychosis and borderline personality disorder. Yet, there is little scientific literature integrating these fields. This symposium will address the phenomenology of psychotic symptoms and borderline personality pathology and their functional effects over the period from puberty through to emerging adulthood.

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9th International Conference on Early Psychosis Borderline personality features and development of psychosis in an ‘Ultra High Risk’ (UHR) population: a case control study

A comparison of psychotic symptoms in youth with borderline personality disorder or first-episode psychosis

Andrew Thompson,1,2,3 Barnaby Nelson,2,3 Andreas Bechdolf,2,4 Andrew Chanen,2,3 Isabelle Domingues,5 Emma McDougall,2 Alison Yung2,3,6

Andrew Chanen,1,2,3 Felix-Antoine Berube,3,4 Martina Jovev,1,2,3 Jennifer Betts,1,2 Hok Pan Yuen,1,2 Richard Kerslake,3 Michael Kaess2,5

1 University of Warwick, 2The University of Melbourne, 3Orygen Youth Health Research Centre, 4University of Cologne, 5University of California, San Diego, 6University of Manchester

1

Background: There is clinical uncertainty whether Borderline Personality Disorder (BPD) traits in those with an ‘at risk mental state’ (ARMS) have an effect on the risk of ‘transition’ to psychosis. We aimed to investigate the relationship between baseline BPD features, risk of transition and type of psychotic disorder experienced.

Objective: To characterise the phenomenology, intensity and functional impact of psychotic experiences in first-presentation BPD patients and to compare these experiences with those from a first episode psychosis (FEP) sample.

Method: A case-control study of ‘Ultra High Risk’ for psychosis (UHR) patients treated at the clinic, between 2004 and 2007. ‘Cases’ were UHR individuals who made the ‘transition’ to full threshold psychotic disorder within 24 months; ‘Control’ group was a matched UHR sample who had not developed a psychotic disorder at 24-months. Individuals were matched on time of entry to the clinic, age and gender. DSM-IV BPD features were assessed from clinical assessments using a structured instrument (SCID-II BPD). Psychosis diagnosis following transition was rated from the clinical files using the OPCRIT computer algorithm. The number of BPD traits and number with full threshold BPD were compared in those who developed psychosis and those who did not. Results: We analysed data from 48 cases and 48 controls. There was no statistically significant difference in the rate of transition to psychosis for those with baseline full-threshold BPD, compared to those without BPD. The number of BPD traits or number with full threshold BPD did not differ by psychosis diagnosis grouping.

The University of Melbourne, 2Orygen Youth Health Research Centre, Orygen Youth Health Clinical Program, 4Université de Montréal, 5University of Heidelberg

3

Methods: A cross-sectional interview was conducted that included the Brief Psychiatric Rating Scale (BPRS) and the Community Assessment of Psychic Experiences (CAPE-42) scores with four groups of patients: BPD + FEP (n = 17), FEP (n = 16), BPD (n = 34), and clinical controls (n = 49). Results: The group with BPD + FEP had the greatest psychopathology, and intensity, frequency and distress with their symptoms. Structured clinical interviews indicated a greater intensity of psychosis in patients with FEP (including BPD + FEP group), but on self-report measures patients with BPD reported a greater frequency of symptoms. Both the BPD and FEP groups reported similar levels of distress and positive symptom frequency. Conclusions: Psychotic symptoms are as common and distressing in BPD as they are in FEP. The co-occurrence of BPD and FEP is associated with particularly severe, frequent and distressing psychotic symptoms. Psychotic symptoms in BPD warrant particular clinical attention.

Conclusions: Co-occurring BPD or BPD features does not appear to strongly influence the risk of short-term transition to psychosis or the risk of developing a non-affective psychotic disorder in this UHR sample.

Phenomenology of psychotic symptoms in borderline personality disorder versus schizophrenia spectrum or affective psychotic disorders: a systematic review Psychotic symptoms and borderline personality disorder in youth Martina Jovev,1,2,3 Louise McCutcheon,2,3 Jennifer Betts,1,2 Andrew Chanen1,2,3 1

The University of Melbourne, 2Orygen Youth Health Research Centre, Orygen Youth Health Clinical Program

3

DSM-5 criterion 9 for Borderline Personality Disorder (BPD) refers to the presence of ‘transient, stress-related paranoid ideation or severe dissociative symptoms’. This criterion suggests possible overlap with first episode psychosis. However, the relationship between psychosis and BPD is neither conceptually clear nor have there been many empirical studies into the treatment, overlap or association between these two disorders. Participants (n = 23) were selected from a clinical file audit study conducted at the Helping Young People Early (HYPE) Program in Melbourne, Australia. HYPE is a specialised indicated prevention and early interventions service for young people (aged 15 to 24) BPD. The present study compared individuals with BPD symptoms who have been identified using the Comprehensive Assessment of At Risk Mental States (CAARMS) as having psychotic symptoms (n = 10) to those without (n = 13). Perceptual abnormalities were the most common symptoms identified. Individuals with psychotic symptoms were more likely to reside in residential care, hostel or inpatient unit at the time of entry into the service. These individuals were also more likely to report affective instability, have a history of aggression toward people or animals, more current antisocial traits and to have been in contact with a mental health professional prior to coming to OYH-CP. Treatment within the HYPE program and other clinical implications will be discussed.

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Félix-Antoine Bérubé,2,4 Michael Kaess,2,5 Jennifer Betts,1,2 Amit Bhaduri,3 John Gleeson,2,6 Martina Jovev,1,2,3 Richard Kerslake,3 Andrea Polari,3 Henry Jackson,1 Andrew Chanen1,2,3 1

The University of Melbourne, 2Orygen Youth Health Research Centre, Orygen Youth Health Clinical Program, 4Université de Montréal, 5University of Heidelberg, 6Australian Catholic University

3

Objectives: There is currently no consensus regarding the phenomenology and severity of hallucinations and other psychotic phenomena associated with Borderline Personality Disorder (BPD). This review investigates the quality, duration, functional impact, distress related to psychotic symptoms occurring in the context of BPD compared with psychotic symptoms occurring in the context of schizophrenia spectrum disorders (SSD) or affective psychotic disorders. It also examines the relations of these symptoms to life-events and dissociative symptoms. Methods: Systematic review following PRISMA guidelines, identifying relevant articles through a comprehensive electronic search strategy, hand searching of relevant publications, consultation of relevant experts in the field as well as forward/backward citation. Included studies compare psychotic symptoms across two or more groups of which one is composed of subjects with BPD and at least one is composed of subjects with SSD or affective disorders. Studies will be reviewed for risks of bias. When quantitative measures are available, effect sizes will be compared among the groups. Results/Conclusion: The review is currently underway. Data extraction and analysis will be completed shortly. The findings will inform discussion about current clinical practice and research with regard to the diagnosis and treatment of psychotic symptoms occurring in the context of BPD. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA

Symposium Session 23 Wednesday, November 19, 2:15–3:40 p.m., Concord B New developments in the early recognition of individuals at risk for or with emerging schizophrenia and bipolar spectrum disorders Chair: Christoph Correll, The Zucker Hillside Hospital; co-chair: Taishiro Kishimoto, Keio University; speakers: Rachel Loewy, John M Kane, Christoph U Correll, Taishiro Kishimoto Schizophrenia and bipolar disorder are among the most debilitating psychiatric disorders. Currently, available management options are still too often insufficient. Long treatment delays and the inability to effectively and safely delay/prevent the full disorder preclude effective targeted and early secondary prevention. Moreover, heterogeneity of psychosis and affective spectrum disorders with genetic and phenomenological overlap complicate the conceptualization, measurement and effective early intervention during the prodromal and first episode phases of schizophrenia and bipolar spectrum disorders. This symposium will target early identification, characterization and measurement in individuals at risk for and with emerging schizophrenia and bipolar spectrum disorders. Rachel Loewy will present data from a series of studies on self-report screening for early psychosis and risk for psychosis, using paper and web-based screening in mental health clinics, university settings and across catchment areas. John Kane will present new methods for the early identification of individuals with emerging/suprathreshold psychotic disorders, utilizing internet and social media strategies involving colleges and high schools. Christoph Correll will review data supporting the fact that an identifiable clinical prodrome exists during the emergence of bipolar disorders. He will focus on the methodological and practical complications in characterizing and operationalizing the bipolar prodrome, which is more complex than the schizophrenia prodrome, being more heterogeneous, pleiotrophic and episodic. Taishiro Kishimoto will present data on the first specific bipolar prodrome interview and rating scale, describing its development and recent validation results in a large group of over 200 adolescents and young adults.

Developing strategies to Reduce DUP in the age of social media and the Internet John M Kane1,2 1

The Zucker Hillside Hospital, 2Hofstra North Shore LIJ School of Medicine, New York, USA Background: Despite the severity of first episode of psychosis (FEP), the duration of untreated psychosis (DUP) averages 2 years, preceded by another 2 years of “prodromal” symptoms. Longer DUP independently predicts readmissions, greater symptom severity and poor quality of life. Although FEP individuals are young and use social media and the Internet widely, these novel technologies have been leveraged insufficiently to reduce DUP. Methods: (1) Development and pilot testing of an e-survey, which can provide anonymous self-assessment for early signs of psychosis, with linkages to educational websites and referrals to FEP programs; (2) collection of social media information and linguistic analysis of at-risk and FEP individuals to identify words/search terms that people with emerging psychotic disorders use in order to facilitate access to these vulnerable, often socially withdrawn individuals; and (3) engagement of high school students in designing surveys of mental health literacy and developing Internet and social media strategies for earlier identification of high-risk and FEP youth. Results: Data will be presented on the development and piloting of the e-survey in 200 college students, linguistic analysis and word count of social media communications provided by 50 first episode psychosis patients from the period before their diagnoses, as well as the results of health literacy surveys in 1,000 high school students. Conclusions: Results from these three linked projects are expected to provide novel information that is critical for the establishment of Internet/ social media points of outreach and engagement, which can be leveraged to identify and refer at-risk and FEP individuals.

Does a prodrome exist in bipolar disorder? Christoph U Correll1,2 1

The Zucker Hillside Hospital, 2Hofstra North Shore LIJ School of Medicine, New York, USA

Screening for early psychosis and risk for psychosis Rachel Loewy University of California San Francisco (UCSF), California, USA Background: Self-report screening for psychosis and psychotic-like symptoms is an important tool used by early detection efforts to reduce the duration of untreated psychosis (DUP) and to identify youth experiencing clinical high risk for psychosis (CHR). Methods: We will describe a series of validation studies of the Prodromal Questionnaire (PQ) and two brief versions of the measure, tested in a variety of settings in multiple languages and countries: early psychosis clinics, general mental health clinics, university courses, and in a prison population. Results: Accuracy of the instrument compared to clinical interview was moderate to strong, varying by setting for both sensitivity (71%–90%) and specificity (58%–87%), with best performance by the brief versions that include information on related distress and impairment. Cutoff selection to maximize accuracy in different settings will be discussed. We will also discuss successful efforts to screen entire catchment areas and utilize new web-based screening as part of broader early psychosis outreach efforts. Conclusions: The Prodromal Questionnaire (PQ) is an effective self-report screening tool for psychosis and psychotic-like symptoms. It is scalable and can be used as part of early identification effort to identify youth with emerging, subthreshold symptoms of psychosis and reduce DUP. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

Background: Despite therapeutic advances, bipolar disorder (BD) remains one of the most debilitating psychiatric disorders. Unfortunately, lacking knowledge about the underlying pathophysiology limit early identification and indicated prevention efforts. Therefore, early characterization of the “prodromal” (subsyndromal) stages of BD has attracted increasing attention, especially in youth, given the early age of first BD symptom onset. Methods: Review of phenomenological manifestations of the prodromal stages preceding syndromal BD, and presentation of the psychometric properties of the newly developed Bipolar Prodrome Symptom ScaleProspective (BPSS-P). Results: While offspring studies in BD are ongoing, clinical “high-risk” BD research is relatively new. So far, retrospective and early prospective data suggest that a clinical mania prodrome exits in a sizeable patient group. Moreover, phenomenologically, the “early mania prodrome” includes nonspecific symptoms of depression and decreasing role and social functioning, character traits (cyclothymic-hypersensitive) that may become more pronounced, as well as potentially more specific, attenuated mania-like symptoms (especially mood swings/lability, racing thoughts and sleep abnormalities). The “late mania prodrome” seems to consist of BD not otherwise specified and, possibly, cyclothymia, where symptoms are either not prolonged or severe/impairing enough to warrant a BD-I diagnosis. Conclusions: Data suggest that a relevant proportion of patients presents with a clinically identifiable “prodromal” symptom stage that may enable indicated prevention. Prospective risk marker studies, using instruments specifically targeting at-risk BD phenomenology, are needed to advance the BD clinical high-risk approach.

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9th International Conference on Early Psychosis Characterizing and operationalizing clinical high-risk for bipolar disorder: description and validation of the Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P) in a psychiatric sample and healthy controls Taishiro Kishimoto Keio University, Japan Aims: To (1) summarize the current terminology, models and emerging criteria for risk for bipolar disorder (BD), and (2) present data on the validation of the first specific bipolar prodrome interview/rating scale. Methods: (1) Review of existing terminology, models and operational criteria for individuals considered at-risk for BD; (2) interview study investigating the psychometric characteristics of the Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P), the first dedicated bipolar at-risk interview/rating scale. Results: Confusion around and inconsistent use of terminology for precursors, risk factors, at-risk states, and risk criteria exists. Several models have been presented, including currently diagnosable disorders as either risk states or potential prodromal presentations, distal and proximal presentations, and incorporating genetic factors in combination with depression or mood instability/cyclothymic features. Analyzing data from 205 youth aged 12–23 years and/or their caregivers with mood-spectrum disorders (n = 129), non-mood-spectrum disorders (n = 34) and healthy controls (n = 42), the BPSS-P had good psychometric properties. This included very high internal consistency (Cronbach’s α = 0.87 and 0.89 for the BPSS-P Mania and Depression Indices), inter-rater reliability (ICC = 0.934–0.985), and convergent validity (r ≥ 0.50 between the BPSS-P Mania Index and the YMRS, GBI-M-10, and CHT; and between the BPSS-P Depression Index and MADRS and CHT). In addition, the BPSS-P had good discriminatory power, not only regarding healthy controls, but also regarding depression spectrum disorder and non-mood spectrum psychiatric disorders. Conclusions: Unified terminology should be developed, to facilitate progress in the early recognition and prevention of BD. The BPSS-P use across multiple settings and predictive validity requires further investigation.

Early lifestyle intervention attenuates antipsychotic-induced weight gain in first episode psychosis Jackie Curtis,1,2 Andrew Watkins,1,3 Simon Rosenbaum,1,2 Scott Teasdale,1,2 Megan Kalucy,1,2 Katherine Samaras,4,5 Philip B. Ward2,6 1

Early Psychosis Programme, The Bondi Centre, South Eastern Sydney Local Health District, 2School of Psychiatry, University of New South Wales, Australia, 3Faculty of Health, University of Technology Sydney, Australia, 4 Department of Endocrinology, St Vincent’s Hospital, Darlinghurst, Australia, 5Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, Australia, 6Schizophrenia Research Unit, South Western Sydney Local Health District, Liverpool, Australia Youth with first episode psychosis (FEP) receiving antipsychotic (AP) medications are at risk of obesity and metabolic syndrome. AP initiation induces rapid deterioration in metabolic health, with up to 77% experiencing clinically significant (>7%) weight-gain within 12 months (1,2). We aimed to determine whether a multidisciplinary, 12-week intervention could attenuate weight gain. Young people with FEP aged 15–25 were enrolled in the ‘Keeping the Body in Mind’ Program, including weekly individualized dietetic monitoring and education and group education, and individualized exercise prescriptions by an exercise physiologist, utilising a supervised on-site gym. Controls were youth with FEP from another service that did not offer lifestyle interventions. 16 participants (56% females, mean age 20.0 ± 2.3 years) completed the intervention, and data were obtained from 12 controls (8% female, mean age 21.7 ± 2.0). Weight gain was substantially lower in the intervention group compared to controls (1.8 kgs ± 3.0 versus 7.8 kgs ± 4.7, p < 0.001). Waist circumference did not increase significantly in the intervention group, whilst waist circumference increased significantly for controls (0·1 cm ± 4·0 versus 7·1 cm ± 3·6, p < 0.001). BP, lipids or glucose did not change significantly for either group. Multidisciplinary early lifestyle interventions can attenuate antipsychotic induced weight gain. References: 1. Correll CU et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009, 302: 1765–73. 2. Perez-Iglesias R et al. Weight gain induced by haloperidol, risperidone and olanzapine after 1 year: findings of a randomized clinical trial in a drug-naive population. Schiz Res 2008, 99: 13–22.

SHAPE (Supporting Health And Promoting Exercise) project for young people with psychosis

Symposium Session 24 Wednesday November 19, 2:15–3:40 p.m., Concord C It’s about time: implementing real world service change to reduce cardiometabolic risk in first episode psychosis Chair: Philip Ward, UNSW; SWSLHD; co-chair: Anna Meneghelli, Azienda Ospedaliera, Ospedale Niguarda Ca’ Granda Dipartimento di Salute Mentale, Programma2000 Milan; speakers: Jackie Curtis, Jo Smith, Edwin HM Lee, Sharman Robertson People living with severe mental illness have twice the rates of overweight/ obesity, twice the rate of diabetes, two to three times the rate of tobacco use and five times greater risk of elevated cholesterol levels than the general population. These risk factors for cardiovascular disease are present from early on in the course of first episode psychosis, and lay the seeds for future morbidity and substantially reduced life expectancy. Increasingly first-episode psychosis services are making efforts to address this problem, including trials of lifestyle interventions focused on increasing physical activity and fitness and improving diet and nutritional status, and the factors that impact physical activity. This symposium will highlight a range of real-world interventions aimed at improving the physical health of youth with first-episode psychosis, developed by services based in Australia, the United Kingdom, Hong Kong and Canada.

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Jo Smith,1,2 Briony Williams,2 Marie Brand,1 David Hickman,2 Eleanor Bradley,2 Jane Richardson,2 Chris Burton,3 Susie Ackner,1 Kat Ferrer,1 Lisa Griffiths,2 Veronica Wilkie,2,4 Rachel Hird-Smith1 1 Worcestershire Health and Care NHS Trust, Worcester, UK, 2University of Worcester, UK, 3Worcestershire County Council, Worcester, UK, 4South Worcestershire Clinical Commissioning Group, Worcester, UK

Physical health problems are common in young people with psychosis who experience poor health and a significant reduction in life expectancy. This is mainly due to premature cardiovascular disease (CVD), underpinned by metabolic disorders like diabetes, and tobacco smoking. Moreover, the mortality gap compared to non-psychotic peers is widening. Yet in many UK EI services, physical health monitoring is not systematic and care plans fail to routinely address the physical health risks for young people with psychosis. This paper will describe one of the first UK ‘real world’ service evaluations of a bespoke EI physical health monitoring and intervention programme for young people with early psychosis called ‘SHAPE’. SHAPE employs nutritionists, exercise physiologists and health trainers to offer a co-ordinated, multi-professional, 12 week wellbeing and exercise programme in a youth focused, socially inclusive setting. Its clinical impact is evaluated at 12 weeks and 12 months. This paper will provide preliminary data on the baseline physical health status of an initial cohort of young people who have accessed the SHAPE Programme to date. It will also describe early outcome data on the clinical impact of SHAPE at 12 weeks on key physical health risk markers and in promoting healthy lifestyle behaviours. It will discuss the acceptability of SHAPE in engaging young people with psychosis to address their physical health needs and in supporting adherence to a structured physical health monitoring and intervention programme. SHAPE has been funded through The Health Foundation (UK) SHINE Award 2014 Programme. © 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

SYMPOSIA Factors for motivational intervention of exercise in patients with psychosis Edwin HM Lee, Jenny TM Lee, Christy LM Hui, WC Chang, Sherry KW Chan, Eric YH Chen Department of Psychiatry, University of Hong Kong, Hong Kong SAR, China Background: Physical activity has many well-known benefits including reduce the risk of cardiovascular disease, diabetes, obesity, hypertension, cancers and early death. Despite the fact that regular physical activity helps to improve functioning and reduce symptoms, the prevalence of physical activity remains low due to multiple biopsychosocial factors. In order to successfully motivate change in physical activity habit among this population, potential factors in predicting change in physical activity behavior was explored. Methods: A cross sectional survey questionnaires using the 5-point-Likert scale were used to measure the physical activity behavior, which include decisional balance, self-efficacy and processes of change, among outpatients who are diagnosed with psychosis with age between 18 and 64, at the out-patient clinic in Hong Kong. Results: 181 outpatients completed the questionnaires and the majority of the subjects were in contemplation stage (51.4%), followed by preparation stage (25.4%), pre-contemplation stage (17.1%) and action and maintenance stages (6.1%). The mean age of this sample was 29.2 years old and 64.2% of subjects were diagnosed as schizophrenia spectrum disorder. Male showed a higher level of intention in changing physical activity behavior than female. In general, the mean of all factors were in the prophesied direction with significant findings except the cons of decisional balance and dramatic relief. Discussion: The findings indicated that different physical activity level was correlated with different physical activity behavior. Motivational intervention with strategies in promoting regular physical activity based on the targeted factors was developed.

© 2014 The Authors Early Intervention in Psychiatry © 2014 Wiley Publishing Asia Pty Ltd Early Intervention in Psychiatry 2014; 8 (Suppl. 1): 1–31

The effect of a multi-modal, 12-week healthy lifestyle, grocery shopping and walking group intervention with and without switch to ziprasidone on metabolic parameters in a Canadian first episode psychosis population Sharman Robertson,1,2,3 Gretchen Conrad,1 Margo Gibson,1 Cindy DesLauriers,1 Crystal Morris,1 Julie Daly,1 Helene Charlebois,1 Leanne Mezzabotta,1 Paul Roy,1 Mark Kaluzienski,1 Walter Hoe,1 Carrie Robertson1 1

The Ottawa Hospital ‘On Track’, First Episode Psychosis Program, Ottawa, Canada, 2The Ottawa Hospital Research Institute, Ottawa, Canada, 3The Royal Ottawa Mental Health Centre, Ottawa, Canada Individuals with psychotic spectrum illnesses are intrinsically vulnerable to central obesity, insulin insensitivity, metabolic syndrome, type-2 diabetes and cardiovascular disease. Higher rates of central obesity and abnormal serum glucose/lipids may exist prior to starting antipsychotic medication. Multiple risk factors have been identified: positive, negative and cognitive symptoms of psychosis, poverty, stigma, metabolically active medications, and poor diet. No clear consensus exists on optimal prevention and treatment of endocrine derangement in first episode psychosis (FEP) populations. This pilot study was conducted at an FEP clinic in Ottawa, Canada. We present data from 25 patients: four were switched to ziprasidone alone; 17 attended a multimodal interdisciplinary intervention (a 12-week Solution Focused Healthy Lifestyle Group, a 12-week Walking Group and a 12-week Grocery Group); four were switched to ziprasidone and attended the multimodal intervention. Baseline mean age was 27.2 years, mean duration of psychosis was 15.7 months. 96% had a schizophrenia-spectrum diagnosis and 24% of the sample was of high risk ethnicity. Patients were on an average of 1.7 medications. Mean group attendance was high: 87% for the Healthy Lifestyle Group, 72% for the Walking Group and 75% for the Grocery Group. 70% of patients lost weight – mean loss of 3.8 kg and mean waist circumference reduction of 3.9 cm. 13% and 17% maintained or gained weight respectively. None developed diabetes or dyslipidemia. Baseline PANSS scores decreased from 60 to 51.6 at 12 weeks. Although this sample is small, results suggest that these interventions can be effective in FEP populations.

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