Effect of time and duration of untreated psychosis on cognitive and social functioning in Chinese patients with first-episode schizophrenia: A 1-year study Nord J Psychiatry Downloaded from informahealthcare.com by Universite De Sherbrooke on 05/02/15 For personal use only.
ANISHA HEERAMUN-AUBEELUCK, NA LIU, FELIX FISCHER, NAN HUANG, FAZHAN CHEN, LEIYING HE, CHENGQING YANG, YANLI LUO, ZHENG LU
Heeramun-Aubeeluck A, Liu N, Fischer F, Huang N, Chen F, He L, Yang C, Luo Y, Lu Z. Effect of time and duration of untreated psychosis on cognitive and social functioning in Chinese patients with first-episode schizophrenia: A 1-year study. Nord J Psychiatry 2014; Early Online:1–8. Background: Duration of untreated psychosis (DUP) is believed to exert a deleterious effect on cognitive and social function. However, to date, results remain inconclusive. Aims: To investigate the effect of time and DUP on cognitive and social functioning in first-episode schizophrenia (FES) subjects in Shanghai, China. Methods: FES patients were subjected to a comprehensive neuropsychological battery, the Personal and Social Performance scale (PSP) and the Positive and Negative Symptoms Scale (PANSS) at baseline, 6 month and 1 year. DUP was defined as the time from onset of first psychotic symptoms to first contact made with psychiatric services. Results: Though the rate of non-completers in our observational study was relatively high (40%), we did not find any significant differences between the completers and non-completers (P-values ⬎ 0.05). Significant impairments in verbal learning and memory and executive function were noted over the course of 1 year. Meanwhile, social function improved significantly over the course of 1 year. Although, DUP did not share any significant relationship with cognitive or social function the effect estimate (range: ⫺ 0.03 to 0.02) of an increase of 1 month in DUP was clinically non-negligible in this study. Conclusions: In Chinese FES patients, the longitudinal course of cognitive function tends to worsen in verbal learning and memory, executive function and motor speed, while that of social function tends to improve. DUP was not found to be associated with cognitive or social deterioration in Chinese FES. • Cognition, Duration of untreated psychosis, First-episode, Schizophrenia, Social function. Zheng Lu, M.D., Shanghai Mental Health Center, Department of Psychiatry, No. 600 South Wan Ping Road, Shanghai 200030, China, E-mail: [email protected]; Accepted 26 May 2014.
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chizophrenia is a severe and chronic clinical syndrome with profoundly disruptive psychopathology involving cognition, emotion, perception and behavior. In China, it has been estimated that approximately 4.25 million people are affected with schizophrenia yearly (1). A more recent survey conducted in Beijing noted that only 58% received treatment and 29% sought help from mental health professionals (2). Schizophrenia remains heavily stigmatized in China (3) and this might contribute to some extent to a longer period of untreated psychosis. Duration of untreated psychosis (DUP) is defined as a continuous period of psychosis that starts from the onset of psychosis and ends at the initiation of treatment (4).
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This is the most commonly used definition of DUP. Until now, there has been no standardized definition of DUP (5). Some authors claimed that the first psychotic symptom even if brief was the start of DUP (6). In other studies, authors stated that the psychotic symptom ought to be present for a defined period of time (7) or that the psychotic episode ought to be rated as at least moderate on a scale such as the Brief Psychiatric Rating Scale (BPRS) or the Positive and Negative Syndrome Scale (PANSS) (8). Though initiation of antipsychotic medication is commonly accepted as the endpoint of psychosis, other studies used different criteria, namely admission to hospital (9), duration or dose of medication or the end DOI: 10.3109/08039488.2014.929738
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of a defined period of treatment (10), and time period until the final diagnosis could be established (11). Though there is no general consensus on the assessment of DUP (5), some assessment scales were developed such as the Nottingham Onset Schedule (NOS) (6) and the Royal Park Multidiagnostic Instrument for psychosis (RPMIP) (12). It is postulated that the longer the DUP, the greater the cognitive deficits that could be explained by the theory of toxic effect of psychosis (13). However, results on the effect of DUP remain inconclusive. In a sample of 113 first-episode psychosis patients, Norman et al. (14) demonstrated that cognitive function was independent of length of DUP. In another sample of 207 firstepisode psychosis patients, Rund et al. (15) also found no relationship between cognitive function and length of DUP. More recent studies also replicated similar findings (16–18). However, there are also studies that found DUP exerting an effect on decline in some cognitive domains such as attention (19), verbal memory (20, 21), executive function (22) and visual memory (23). de Haan et al. (24) followed 205 schizophrenia patients over 10 years and reported no association between DUP and outcome measures. However, other studies reported that a short DUP was associated with a good outcome (25–27). A more recent retrospective study conducted by Primavera et al. (28) reported that shorter DUP correlated with better functioning. Unlike age, gender and premorbid adjustment, DUP is one parameter that can potentially be modified (29, 30). According to the latest survey from the World Health Organization (31), 24 million people worldwide are affected with schizophrenia. In China, research on DUP is scarce, thus highlighting the importance of investigating DUP in Chinese first-episode schizophrenia (FES) patients.
Aims This study aimed to report: 1) the longitudinal course of cognitive and social functioning in Chinese FES patients; and 2) the effect of DUP on cognitive and social functioning in Chinese FES.
Materials and Methods Study design The “shi yi wu”, also known as the National 11th Fiveyear Project was conducted in six centers in different parts of China, namely Beijing (three centers), Shanghai, Sichuan and Hunan. In brief, it consisted of identifying Chinese FES patients who sought or were referred for treatment at the outpatient department in one of the above-mentioned centers. This article is focused on reporting the findings of FES patients who were recruited at the Shanghai
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Mental Health Center in Shanghai. At the time of entry into this study, all patients were drug-naive or had been taking low doses of antipsychotic or other psychotropic medication not exceeding 2 weeks. The nature of this study was explained to patients and relatives and written consent was requested for participation in this project. It should be pointed out that as part of an ethical consideration, patients were free to leave the study whenever they wanted or relatives were free to withdraw the patients from the study. This study was approved by the Shanghai Mental Health Center Ethics Committee Board. From 8 August 2009 until 20 February 2011, all referrals to the Shanghai Mental Health Center were screened for patients using the Structured Clinical Interviews for DSM-IV, patient edition (SCID-I/P) assessment for those who met the following criteria: 1) aged 16–45 years; 2) meeting DSM-IV criteria for a diagnosis of schizophrenia; and 3) no prior treatment with antipsychotic or other psychotropic medication or if previously treated, a total life time of treatment of less than 2 weeks. The exclusion criteria were as follows: 1) organic brain diseases or other clinically significant concurrent physical illness; 2) history of head injury, loss of consciousness for more than 1 h, or significant mental retardation; 3) current (past 3 months) alcohol and substance abuse history or past history of dependence; 4) contraindications to use of olanzapine, risperidone or aripiprazole; 5) other psychotic disorders like schizoaffective disorder, brief psychotic disorder or psychosis not otherwise specified. There were 103 patients who met the inclusion criteria but two refused to participate. Thus, at baseline, 101 patients underwent a complete evaluation of clinical symptoms and laboratory tests before being randomly assigned to treatment. The medication protocol consisted of choosing one of the commonly used second-generation antipsychotics: olanzapine (5–20 mg/day), risperidone (3–6 mg/day) or aripiprazole (10–20 mg/day). In case of poor response, the treating psychiatrist could change the drug to another of the three chosen antipsychotics. In cases of significant extrapyramidal effects, patients were administered trihexyphenidyl (5–15 mg/day). Small doses of intravenous lorazepam (1–2 mg) were used for the management of acute behavioral disturbances in some patients. The interviewers assessing cognitive and social functioning were blinded to the DUP status of the patients throughout the study. All clinical assessments were conducted at baseline, 6 months and 1 year. The sociodemographic data has been summarized in Table 1. NORD J PSYCHIATRY·EARLY ONLINE·2015
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Table 1. Cognitive domains and cognitive tests used. Cognitive domain Working memory Processing speed Executive functioning Verbal Learning/memory Visual Memory Motor speed
Cognitive tests and scores used 1) Paced Auditory Serial; Addition Test, 50 items (PASAT)—Total correct score; 2) WMS-III spatial span—Total score 1) WAIS-III Digit Symbol—Total count; 2) WAIS-III symbol search—Total count; 3) Trail making test A—Time taken 1) Color Trails II—total time taken to complete lines 1) Hopkins Verbal Learning Test-Revised (HVLT)—Total learning and delayed recall 1) Brief Visuospatial Memory Test-Revised (BVMT)—Total learning and delayed recall 1) Grooved Pegboard test—Time taken for insertion with dominant and non-dominant hand
WMS-III, Wechsler Memory Scale, 3rd edition; WAIS-III, Wechsler Adult Intelligence Scale.
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Duration of untreated psychosis (DUP) DUP was defined as the number of months from onset of psychotic phenomena to first contact made with the mental health services. Since there are no validated Chinese assessment scales for DUP assessment in China, data relating to onset of psychosis was collected during SCID-I/P interviews with the patient, as well as interviews with close relative(s) and/or carer(s), and clinical notes (17, 32). Psychosis was defined as the time of emergence of psychotic symptoms as dated by patients/ relatives (33). The inter-rater reliability was assessed by using Pearson’s correlation coefficient and was deemed satisfactory (⬎ 0.75).
Measures The clinical symptoms of psychosis were assessed by the Mandarin Chinese version of the PANSS scale consisting of 30 items and seven levels of psychopathology. The Chinese PANSS scale proved to be reliable and valid in Chinese patients (34). The inter-rater reliability for this study was deemed satisfactory (Pearson’s correlation coefficient ⬎ 0.75). Social functioning was assessed by the Personal and Social Performance scale (PSP) developed from the Social and Occupational Functioning Assessment Scales (SOFAS). Scores are from 0 to 100 points and are based on the assessment of four objective indicators: (a) socially useful activities; (b) personal and social relationships; (c) self-care; and (d) disturbing and aggressive behaviors. The Chinese version of the PSP demonstrated good reliability, validity and sensitivity to change over time (35). Inter-rater reliability assessed by Pearson’s correlation coefficient was deemed satisfactory (⬎ 0.75). Patients also underwent an extensive neuropsychological battery designed by the Institute of Mental Health, Peking University in collaboration with the University of California, San Diego HIV Neurobehavioral Research Center. The cognitive tests along with the corresponding scores used for analysis and their relevant cognitive domains are described in Table 1. These tests demonstrated cross-cultural validity in recent studies (36). NORD J PSYCHIATRY·EARLY ONLINE·2015
All the clinical assessments were conducted by trained personnel at the Shanghai Mental Health Center.
Statistical analysis We conducted complete case analysis and excluded all persons who did not complete all cognitive tests at all times. We assessed differences in descriptive variables between completers and non-completers at baseline in order to identify possible attrition bias. All raw scores of the cognitive tests were converted to standardized z-scores, with mean and standard deviation derived from the baseline test. For each cognitive domain, the mean score of the respective z-scores was then calculated. Test scores at different time intervals and effect of DUP on cognitive and social function were modeled within a multilevel analysis framework to account for repeated measurement and inter-individual variability. At first, we fitted a multilevel model for each cognitive domain with fixed effects for 6 months and 1 year. We implemented two separate effects because we suspected that a linear association with 1 year having twice the effect of 6 months might not be suitable. The variability of patients was entered as a random effect in the model. The resulting effect estimates for 6 months and 1 year including a 95% confidence interval are the outcomes to assess research question 1—the longitudinal course of cognitive and social function. To assess the effect of DUP on cognitive and social function at each time interval (baseline, 6 months and 1 year), we included three interaction terms (DUP⫻ baseline, DUP ⫻ 6 months, DUP ⫻ 1 year) in the models above. We present a likelihood ratio test between models with and without DUP terms based on a chi-square distribution in order to assess overall model fit increase as well as single effect estimates and P-values for each of the interaction terms. As we suspected a possibly weaker effect of an additional month of DUP at higher levels of DUP, we fitted those models also after log-transformation of DUP to control.
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Table 2. Socio-demographic and clinical characteristics of completers and non-completers.
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Non-completers (n ⫽ 63) Gender (%/n) Female Male Age (mean/s) Schooling years (mean/s) DUP in months (mean/s) Marital status (%/n) Divorced Married Remarried Single Widowed Drugs used (%/n) Aripiprazole Olanzapine Risperidone Drug switch (%/n) No change Aripiprazole Olanzapine Risperidone
Completers (n ⫽ 38)
Combined (n ⫽ 101)
Test statistics χ2 ⫽ 1.1; P ⫽ 0.29
56% (35) 44% (28) 26.7 (6.8) 13.1 (2.7) 9.8 (10.8)
45% (17) 55% (21) 25.9 (7.3) 12.2 (3.5) 9.8 (10.6)
51% (52) 49% (49) 26.4 (7.0) 12.8 (3.1) 9.8 (10.7)
6% (4) 16% (10) 0 % (0) 76% (48) 2 % (1)
8% (3) 21% (8) 3 % (1) 68% (26) 0 % (0)
7% (7) 18% (18) 1% (1) 73% (74) 1 % (1)
32% (20) 30% (19) 38% (24)
37% (14) 37% (14) 26% (10)
34% (34) 33% (33) 34% (33)
F ⫽ 0.52; P ⫽ 0.47 F ⫽ 2; P ⫽ 0.16 F ⫽ 0.06; P ⫽ 0.80 χ2 ⫽ 2.9; P ⫽ 0.58
χ2 ⫽ 1.5; P ⫽ 0.48
χ2 ⫽ 0.16; P ⫽ 0.98 62% (39) 6% (4) 25% (16) 6% (4)
63% (24) 5 % (2) 24% (9) 8% (3)
62% (63) 6% (6) 25% (25) 7% (7)
s, standard deviation; DUP, duration of untreated psychosis.
Results
Effect of DUP on cognitive and social functioning
Demographics and clinical characteristics
Table 4 shows the effect estimates of DUP on outcomes. For all outcomes, the omnibus likelihood
The demographic and clinical comparisons of all participants (completers and non-completers) are presented in Table 2. As can be seen, there were no significant differences between those who abandoned the study over the course of 1 year and those who continued (all P-values ⬎ 0.05). The main reasons for our non-completers were that some were no longer willing to be part of the study, had lost interest in the test, found the tests difficult or were unable to come for follow-up assessments. Some patients were probably experiencing marked social dysfunction and hence were unable to comprehend and fulfill the given tasks. The mean raw scores for completers (n ⫽ 38) in each cognitive domain and social function tests are displayed in Table 3.
Longitudinal course of cognitive and social functioning We found a significant impairment of about 1 ⫻ standard deviation in verbal learning and memory, and about half a standard deviation in executive functioning at the 6-month and 1-year follow-up compared with baseline. Motor speed was significantly lower at 1 year while working memory was slightly increased at the 1-year follow-up. In all other cognitive tests, no significant change was observed (Fig. 1). On the other hand, we found a stable pattern of increasing social functioning over the course of 1 year and a difference between baseline and the 1-year follow-up of about 2 ⫻ standard deviations.
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Table 3. Raw mean (standard deviation, s) scores of completers of cognitive and social function tests.
Tests Working memory PASAT Spatial span Processing speed Digit symbol Symbol search Trail A Executive function Color Trail line 2 Verbal learning/memory HVLT total learning HVLT delayed recall Visual memory BVMT total learning BVMT delayed recall Motor speed GP Dominant hand GP non-dominant hand PSP
Baseline, mean (s), n ⫽ 38
6-month, mean (s), n ⫽ 38
1-year, mean (s), n ⫽ 38
33.9 (9.8) 16.6 (3.7)
37.3 (8.9) 16.4 (2.5)
40.0 (9.5) 16.0 (2.8)
60.5 (14.5) 28.0 (9.0) 44.8 (18.2)
62.8 (16.5) 29.7 (10.8) 39.2 (16.9)
67.7 (13.9) 31.0 (11.0) 35.0 (13.8)
112.8 (49.1)
91.8 (30.5)
83.5 (28.1)
23.8 (4.6) 7.7 (2.2)
19.9 (5.3) 5.9 (2.5)
19.1 (5.6) 6.0 (2.7)
21.8 (7.1) 9.0 (3.1)
21.6 (7.0) 8.6 (2.7)
23.4 (7.8) 8.8 (3.2)
80.6 (17.7) 97.5 (44.1) 36.7 (15.6)
77.5 (21.6) 93.1 (37.9) 53.4 (16.8)
74.1 (16.4) 84.0 (17.4) 67.1 (10.9)
PASAT, Paced Addition Serial Addition Test; HVLT, Hopkins Verbal Learning Test, Revised; BVMT, Brief Visuospatial Memory Test, Revised; GP, Grooved Pegboard Test; PSP, Personal and Social Performance scale. NORD J PSYCHIATRY·EARLY ONLINE·2015
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Fig. 1. The longitudinal course of cognitive function.
ratio test revealed that inclusion of DUP in the statistical model did not result in an increased fit, for neither cognitive nor social functioning. However, effect estimates of an additional month of DUP ranged between ⫺ 0.03 and 0.02, which seemed small at first sight. Although statistically non-significant, clinically relevant effects cannot be ruled out due to small sample size. Sensitivity analysis with log-transformed DUP did not change this picture. NORD J PSYCHIATRY·EARLY ONLINE·2015
Discussion The aims of this study were to examine the effects of time and DUP on cognitive and social functioning. The main findings indicate that over time: 1) there is significant deterioration in verbal learning and memory and executive function; 2) a general worsening in performance of motor speed and a minor increase in performance in working memory; and 3) social function improves over time.
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Table 4. Effect of duration of untreated psychosis (DUP) on cognitive and social functions.
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Baseline
Effect of DUP Working memory Processing speed Executive function Verbal learning/memory Visual memory Motor speed PSP Effect of log DUP Working memory Processing speed Executive function Verbal learning/memory Visual memory Motor speed PSP
6-month
1-year
Overall test
Effect estimate
P-value
Effect estimate
P-value
Effect estimate
P-value
P-value
⫺ 0.01 0.01 0.02 0.01 0.00 ⫺ 0.01 ⫺ 0.01
0.564 0.306 0.079 0.531 0.815 0.221 0.494
⫺ 0.01 ⫺ 0.02 0.01 0.01 0.00 0.01 ⫺ 0.03
0.233 0.051 0.302 0.430 0.879 0.454 0.038
⫺ 0.02 ⫺ 0.01 0.01 ⫺ 0.01 ⫺ 0.01 0.00 ⫺ 0.01
0.072 0.517 0.262 0.519 0.324 0.707 0.409
0.205 0.053 0.330 0.266 0.521 0.193 0.202
⫺ 0.07 0.00 0.03 0.00 ⫺ 0.01 ⫺ 0.14 0.00
0.482 0.999 0.721 0.986 0.923 0.195 0.994
⫺ 0.12 ⫺ 0.18 0.11 0.09 ⫺ 0.04 0.00 ⫺ 0.20
0.227 0.037 0.227 0.513 0.765 0.990 0.109
⫺ 0.16 ⫺ 0.09 0.09 ⫺ 0.12 ⫺ 0.04 ⫺ 0.04 ⫺ 0.11
0.112 0.263 0.348 0.391 0.779 0.722 0.385
0.360 0.129 0.595 0.307 0.987 0.491 0.347
PSP, Personal and Social Performance scale.
Meanwhile, DUP did not share any relationship with cognitive or social function but seemed to exert a small yet clinically non-negligible effect.
Effect of time on cognitive function Cognitive deficits are common in schizophrenia and are even deemed core features (37, 38). We found that longitudinal assessment of cognitive function had no significant differences over time except in verbal learning, and memory and executive function. Our findings confirm that even in Chinese FES verbal memory is affected (39– 41). Though Rund et al. (42) claimed that cognitive deficits were stable in first-episode psychosis patients, others have found impairments in other domains such as executive function (19, 41, 43, 44). We believe that the general decrease in motor speed could be partially related to the effect of antipsychotics and we do not exclude the possibility that since this test was the last in the battery of tests, patients had lost interest in the process.
Effect of time on social function The longitudinal course of social function improved over 1 year. There was a considerable increase in PSP scores from baseline to 1 year in all patients, which could be attributed to the effectiveness of the antipsychotics used. Similar improvements were noted by Popolo et al. (45).
Effect of DUP on cognitive function We found that DUP did not result into any increased model fit with cognitive function. Similar findings were obtained after logarithmic transformation of the DUP. Our findings correlate with those of Ayres et al. (16),
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Goldberg et al. (17) and Malla et al. (18). However, there are some studies reporting a longer DUP leading to impaired performance on different cognitive domains such as Verbal IQ and verbal working memory (21), attention (19) and visual memory (23). Differences in findings might be due to different sets of cognitive tests used and different mean DUP. Despite growing evidence that cognitive deficits are present long before the onset of schizophrenia (46, 47) and data supporting neurodevelopmental hypothesis for cognitive impairment in schizophrenia (48, 49), the toxic effect of psychosis cannot be completely dismissed (18). In our study, the small effect estimate of the DUP effect seems to illustrate this viewpoint.
Effect of DUP on social function Deterioration in social function in FES occurs after the onset of disease and shows mild improvement over time (50). We found that there was no increased model fit between DUP and social function. Some studies reported that a longer DUP led to a deterioration in social function (26, 28, 29, 32). However, it should be noted that these studies used the Global Assessment of Functioning (GAF) or the Social Function Scale (SFS) scale for measuring social function and had a longer median DUP and follow-ups. In a systematic review, Marshall et al. (27), found a modest association between length of DUP and functional outcome, and it was noted that outcome was independent of premorbid adjustment.
Limitations Despite our homogeneous sample of FES, limitations that came up were: 1) missing data for cognitive assessments NORD J PSYCHIATRY·EARLY ONLINE·2015
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contributing to increased Type II statistical error; 2) the potential effects of antipsychotics interfering with cognitive and social functioning were not investigated. However, recent findings from the Clinical Antipsychotics Trial of Intervention Effectiveness (CATIE) trial showed no significant differences in neurocognitive functioning in response to medications (51); 3) DUP was assessed through structured clinical interview and not through use of a scale.
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Conclusions Chinese FES patients are impaired in verbal learning and memory and executive function over the course of 1 year. Social function improves significantly with the effect of antipsychotics; hence, early detection and regular medication are important for improving functional outcome. DUP was not found to be associated with cognitive or social deterioration in Chinese FES.
Role of funding source The “di shi yi wu” or National Five-year plan was supported by the National Key Project of Scientific and Technical Supporting Programs and funded by the Ministry of Science & Technology of China (No. 2007BAI17B04). Acknowledgment—The authors wish to extend their gratitude to Dr. Rainer Leonhart of the University of Freiburg for his assistance in statistical analysis.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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A HEERAMUN-AUBEELUCK ET AL. 30. Fusar-Poli P, Meneghelli L, Valmaggia P, Allen P, Galvan F, McGuire P, et al. Duration of untreated prodromal symptoms and 12-month functional outcome of individuals at risk of psychosis. Br J Psychiatry 2009;194:181–2. 31. World Health Organization. http://www.who.int/mental_health/ management/schizophrenia/en/ (last accessed October 3, 2013). 32. Barnes TRE, Leeson VC, Mutsatsa SH, Watt HC, Hutton SB, Joyce EM. Duration of untreated psychosis and social function: 1-year follow-up study of first-episode schizophrenia. Br J Psychiatry 2008;193:203–9. 33. Browne S, Gervin M, Waddington JL, Larkin C, O’Callaghan E. Determinants of quality of life at first presentation with schizophrenia. Br J Psychiatry 2000;176:173–6. 34. Si T, Yang J, Shu L, Wang X, Kong Q, Zhou M, et al. The reliability, validity of PANSS and its implications. Chinese Ment Health J 2004;18:45–7 (in Chinese). 35. Si T, Shu L, Su Y, Tian C, Yan J, Cheng J, et al. The Chinese version of the Personal and Social Performance Scale (PSP): Validity and reliability. Psychiatry Res 2011;185:275–9. 36. Cysique LA, Jin H, Franklin Jr. DR, Morgan EE, Shi C, Yu X, et al. Neurobehavioral effects of HIV-1 infection in China and the U.S.: A pilot study. J Int Neuropsychol Soc 2007;13:781–90. 37. Elvevåg B, Goldberg TE. Cognitive impairment in schizophrenia is the core of the disorder. Crit Rev Neurobiol 2000;14:1–21. 38. Heinrichs RW. The primacy of cognition in schizophrenia. Am Psychol 2005;60:229–42. 39. Bozikas VP, Andreou C. Longitudinal studies of cognition in first-episode psychosis: A systematic review of the literature. Aust N Z J Psychiatry 2011;45:93–108. 40. Rodríguez-Sánchez JM, Pérez-Iglesias R, González-Blanch C, Pelayo-Téran JM, Mata I, Martínez O, et al. 1-year follow-up study of cognitive function in first-episode non-affective psychosis. Schizophr Res 2008;104:165–74. 41. Aas M, Dazzan P, Mondelli V, Melle I, Murray RM, Pariante CM. A systematic review of cognitive function in first-episode psychosis including a discussion on childhood trauma, stress and inflammation. Front Psychiatr 2014;4:1–13. 42. Rund BR, Melle I, Friis S, Johannessen JO, Larsen TK, Midboe LJ, et al. The course of neurocognitive functioning in first-episode psychosis and its relation to premorbid adjustment, duration of untreated psychosis, and relapse. Schizophr Res 2007;91:132–40. 43. Saleem MM, Harte MK, Marshall KM, Scally A, Brewin A, Neill JC. First-episode psychosis patients show impaired cognitive functions—A study of a South Asian population in the UK. J. Psychopharmacol 2013;27:336–73.
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44. Rodríguez-Sánchez JM, Crespo-Facorro, González-Blanch C, Pérez-Iglesias R, Vásquez-Barquero JL. Cognitive dysfunction in first-episode psychosis: The processing speed hypothesis. Br J Psychiatry 2007;191:s107–10. 45. Popolo R, Vinci G, Balbi A. Cognitive function, social functioning and quality of life in first-episode psychosis: A 1-year longitudinal study. Int J Clin Pract 2010;14:33–40. 46. Owens DGC, Johnstone EC. Precursors and prodromata of schizophrenia: Findings from the Edinburgh High Risk Study and their literature context. Psychol Med 2006;36:1501–14. 47. Reichenberg A, Caspi A, Harrington HL, Houts R, Keefe RS, Murray RM, et al. Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: A 30-year study. Am J Psychiatry 2010;167:160–9. 48. van Os J, Kapur S. Schizophrenia. Lancet 2009;374: 635–45. 49. Kinros J, Reichenberg A, Frangou S. The neurodevelopmental theory of schizophrenia: Evidence from studies of early onset cases. Isr J Psychiatry Relat Sci 2010;47:110–17. 50. Jaracz K, Górna K, Rybabowski F. Social functioning in firstepisode schizophrenia. A prospective follow-up study. Arch Psychiatry Psychother 2007;4:19–27. 51. Swartz MS, Stroup TS, McEvoy JP, Davis SM, Rosenheck RA, Keefe RS, et al. What CATIE found: Results from the schizophrenia trial. Psychiatr Serv 2008;59:500–6. Anisha Heeramun-Aubeeluck, Psychiatry, Tongji University, Shanghai, China. Na Liu, Psychiatry, Shanghai Mental Health Centre, Shanghai, China. Felix Fischer, Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany. Nan Huang, Psychiatry, Shanghai Mental Health Centre, Shanghai, China. Fazhan Chen, Psychiatry, Shanghai Mental Health Centre, Shanghai, China. Leiying He, Psychiatry, Shanghai Mental Health Centre, Shanghai, China. Chengqing Yang, Psychiatry, Shanghai Mental Health Centre, Shanghai, China. Yan-Li Luo, Psychiatry, Shanghai Mental Health Centre, Shanghai, China. Zheng Lu, Psychiatry, Shanghai Mental Health Centre, Shanghai, China.
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ANISHA HEERAMUN-AUBEELUCK, NA LIU, FELIX FISCHER, NAN HUANG, FAZHAN CHEN, LEIYING HE, CHENGQING YANG, YANLI LUO, ZHENG LU
Heeramun-Aubeeluck A, Liu N, Fischer F, Huang N, Chen F, He L, Yang C, Luo Y, Lu Z. Effect of time and duration of untreated psychosis on cognitive and social functioning in Chinese patients with first-episode schizophrenia: A 1-year study. Nord J Psychiatry 2014; Early Online:1–8. Background: Duration of untreated psychosis (DUP) is believed to exert a deleterious effect on cognitive and social function. However, to date, results remain inconclusive. Aims: To investigate the effect of time and DUP on cognitive and social functioning in first-episode schizophrenia (FES) subjects in Shanghai, China. Methods: FES patients were subjected to a comprehensive neuropsychological battery, the Personal and Social Performance scale (PSP) and the Positive and Negative Symptoms Scale (PANSS) at baseline, 6 month and 1 year. DUP was defined as the time from onset of first psychotic symptoms to first contact made with psychiatric services. Results: Though the rate of non-completers in our observational study was relatively high (40%), we did not find any significant differences between the completers and non-completers (P-values ⬎ 0.05). Significant impairments in verbal learning and memory and executive function were noted over the course of 1 year. Meanwhile, social function improved significantly over the course of 1 year. Although, DUP did not share any significant relationship with cognitive or social function the effect estimate (range: ⫺ 0.03 to 0.02) of an increase of 1 month in DUP was clinically non-negligible in this study. Conclusions: In Chinese FES patients, the longitudinal course of cognitive function tends to worsen in verbal learning and memory, executive function and motor speed, while that of social function tends to improve. DUP was not found to be associated with cognitive or social deterioration in Chinese FES. • Cognition, Duration of untreated psychosis, First-episode, Schizophrenia, Social function. Zheng Lu, M.D., Shanghai Mental Health Center, Department of Psychiatry, No. 600 South Wan Ping Road, Shanghai 200030, China, E-mail: [email protected]; Accepted 26 May 2014.
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chizophrenia is a severe and chronic clinical syndrome with profoundly disruptive psychopathology involving cognition, emotion, perception and behavior. In China, it has been estimated that approximately 4.25 million people are affected with schizophrenia yearly (1). A more recent survey conducted in Beijing noted that only 58% received treatment and 29% sought help from mental health professionals (2). Schizophrenia remains heavily stigmatized in China (3) and this might contribute to some extent to a longer period of untreated psychosis. Duration of untreated psychosis (DUP) is defined as a continuous period of psychosis that starts from the onset of psychosis and ends at the initiation of treatment (4).
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This is the most commonly used definition of DUP. Until now, there has been no standardized definition of DUP (5). Some authors claimed that the first psychotic symptom even if brief was the start of DUP (6). In other studies, authors stated that the psychotic symptom ought to be present for a defined period of time (7) or that the psychotic episode ought to be rated as at least moderate on a scale such as the Brief Psychiatric Rating Scale (BPRS) or the Positive and Negative Syndrome Scale (PANSS) (8). Though initiation of antipsychotic medication is commonly accepted as the endpoint of psychosis, other studies used different criteria, namely admission to hospital (9), duration or dose of medication or the end DOI: 10.3109/08039488.2014.929738
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of a defined period of treatment (10), and time period until the final diagnosis could be established (11). Though there is no general consensus on the assessment of DUP (5), some assessment scales were developed such as the Nottingham Onset Schedule (NOS) (6) and the Royal Park Multidiagnostic Instrument for psychosis (RPMIP) (12). It is postulated that the longer the DUP, the greater the cognitive deficits that could be explained by the theory of toxic effect of psychosis (13). However, results on the effect of DUP remain inconclusive. In a sample of 113 first-episode psychosis patients, Norman et al. (14) demonstrated that cognitive function was independent of length of DUP. In another sample of 207 firstepisode psychosis patients, Rund et al. (15) also found no relationship between cognitive function and length of DUP. More recent studies also replicated similar findings (16–18). However, there are also studies that found DUP exerting an effect on decline in some cognitive domains such as attention (19), verbal memory (20, 21), executive function (22) and visual memory (23). de Haan et al. (24) followed 205 schizophrenia patients over 10 years and reported no association between DUP and outcome measures. However, other studies reported that a short DUP was associated with a good outcome (25–27). A more recent retrospective study conducted by Primavera et al. (28) reported that shorter DUP correlated with better functioning. Unlike age, gender and premorbid adjustment, DUP is one parameter that can potentially be modified (29, 30). According to the latest survey from the World Health Organization (31), 24 million people worldwide are affected with schizophrenia. In China, research on DUP is scarce, thus highlighting the importance of investigating DUP in Chinese first-episode schizophrenia (FES) patients.
Aims This study aimed to report: 1) the longitudinal course of cognitive and social functioning in Chinese FES patients; and 2) the effect of DUP on cognitive and social functioning in Chinese FES.
Materials and Methods Study design The “shi yi wu”, also known as the National 11th Fiveyear Project was conducted in six centers in different parts of China, namely Beijing (three centers), Shanghai, Sichuan and Hunan. In brief, it consisted of identifying Chinese FES patients who sought or were referred for treatment at the outpatient department in one of the above-mentioned centers. This article is focused on reporting the findings of FES patients who were recruited at the Shanghai
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Mental Health Center in Shanghai. At the time of entry into this study, all patients were drug-naive or had been taking low doses of antipsychotic or other psychotropic medication not exceeding 2 weeks. The nature of this study was explained to patients and relatives and written consent was requested for participation in this project. It should be pointed out that as part of an ethical consideration, patients were free to leave the study whenever they wanted or relatives were free to withdraw the patients from the study. This study was approved by the Shanghai Mental Health Center Ethics Committee Board. From 8 August 2009 until 20 February 2011, all referrals to the Shanghai Mental Health Center were screened for patients using the Structured Clinical Interviews for DSM-IV, patient edition (SCID-I/P) assessment for those who met the following criteria: 1) aged 16–45 years; 2) meeting DSM-IV criteria for a diagnosis of schizophrenia; and 3) no prior treatment with antipsychotic or other psychotropic medication or if previously treated, a total life time of treatment of less than 2 weeks. The exclusion criteria were as follows: 1) organic brain diseases or other clinically significant concurrent physical illness; 2) history of head injury, loss of consciousness for more than 1 h, or significant mental retardation; 3) current (past 3 months) alcohol and substance abuse history or past history of dependence; 4) contraindications to use of olanzapine, risperidone or aripiprazole; 5) other psychotic disorders like schizoaffective disorder, brief psychotic disorder or psychosis not otherwise specified. There were 103 patients who met the inclusion criteria but two refused to participate. Thus, at baseline, 101 patients underwent a complete evaluation of clinical symptoms and laboratory tests before being randomly assigned to treatment. The medication protocol consisted of choosing one of the commonly used second-generation antipsychotics: olanzapine (5–20 mg/day), risperidone (3–6 mg/day) or aripiprazole (10–20 mg/day). In case of poor response, the treating psychiatrist could change the drug to another of the three chosen antipsychotics. In cases of significant extrapyramidal effects, patients were administered trihexyphenidyl (5–15 mg/day). Small doses of intravenous lorazepam (1–2 mg) were used for the management of acute behavioral disturbances in some patients. The interviewers assessing cognitive and social functioning were blinded to the DUP status of the patients throughout the study. All clinical assessments were conducted at baseline, 6 months and 1 year. The sociodemographic data has been summarized in Table 1. NORD J PSYCHIATRY·EARLY ONLINE·2015
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Table 1. Cognitive domains and cognitive tests used. Cognitive domain Working memory Processing speed Executive functioning Verbal Learning/memory Visual Memory Motor speed
Cognitive tests and scores used 1) Paced Auditory Serial; Addition Test, 50 items (PASAT)—Total correct score; 2) WMS-III spatial span—Total score 1) WAIS-III Digit Symbol—Total count; 2) WAIS-III symbol search—Total count; 3) Trail making test A—Time taken 1) Color Trails II—total time taken to complete lines 1) Hopkins Verbal Learning Test-Revised (HVLT)—Total learning and delayed recall 1) Brief Visuospatial Memory Test-Revised (BVMT)—Total learning and delayed recall 1) Grooved Pegboard test—Time taken for insertion with dominant and non-dominant hand
WMS-III, Wechsler Memory Scale, 3rd edition; WAIS-III, Wechsler Adult Intelligence Scale.
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Duration of untreated psychosis (DUP) DUP was defined as the number of months from onset of psychotic phenomena to first contact made with the mental health services. Since there are no validated Chinese assessment scales for DUP assessment in China, data relating to onset of psychosis was collected during SCID-I/P interviews with the patient, as well as interviews with close relative(s) and/or carer(s), and clinical notes (17, 32). Psychosis was defined as the time of emergence of psychotic symptoms as dated by patients/ relatives (33). The inter-rater reliability was assessed by using Pearson’s correlation coefficient and was deemed satisfactory (⬎ 0.75).
Measures The clinical symptoms of psychosis were assessed by the Mandarin Chinese version of the PANSS scale consisting of 30 items and seven levels of psychopathology. The Chinese PANSS scale proved to be reliable and valid in Chinese patients (34). The inter-rater reliability for this study was deemed satisfactory (Pearson’s correlation coefficient ⬎ 0.75). Social functioning was assessed by the Personal and Social Performance scale (PSP) developed from the Social and Occupational Functioning Assessment Scales (SOFAS). Scores are from 0 to 100 points and are based on the assessment of four objective indicators: (a) socially useful activities; (b) personal and social relationships; (c) self-care; and (d) disturbing and aggressive behaviors. The Chinese version of the PSP demonstrated good reliability, validity and sensitivity to change over time (35). Inter-rater reliability assessed by Pearson’s correlation coefficient was deemed satisfactory (⬎ 0.75). Patients also underwent an extensive neuropsychological battery designed by the Institute of Mental Health, Peking University in collaboration with the University of California, San Diego HIV Neurobehavioral Research Center. The cognitive tests along with the corresponding scores used for analysis and their relevant cognitive domains are described in Table 1. These tests demonstrated cross-cultural validity in recent studies (36). NORD J PSYCHIATRY·EARLY ONLINE·2015
All the clinical assessments were conducted by trained personnel at the Shanghai Mental Health Center.
Statistical analysis We conducted complete case analysis and excluded all persons who did not complete all cognitive tests at all times. We assessed differences in descriptive variables between completers and non-completers at baseline in order to identify possible attrition bias. All raw scores of the cognitive tests were converted to standardized z-scores, with mean and standard deviation derived from the baseline test. For each cognitive domain, the mean score of the respective z-scores was then calculated. Test scores at different time intervals and effect of DUP on cognitive and social function were modeled within a multilevel analysis framework to account for repeated measurement and inter-individual variability. At first, we fitted a multilevel model for each cognitive domain with fixed effects for 6 months and 1 year. We implemented two separate effects because we suspected that a linear association with 1 year having twice the effect of 6 months might not be suitable. The variability of patients was entered as a random effect in the model. The resulting effect estimates for 6 months and 1 year including a 95% confidence interval are the outcomes to assess research question 1—the longitudinal course of cognitive and social function. To assess the effect of DUP on cognitive and social function at each time interval (baseline, 6 months and 1 year), we included three interaction terms (DUP⫻ baseline, DUP ⫻ 6 months, DUP ⫻ 1 year) in the models above. We present a likelihood ratio test between models with and without DUP terms based on a chi-square distribution in order to assess overall model fit increase as well as single effect estimates and P-values for each of the interaction terms. As we suspected a possibly weaker effect of an additional month of DUP at higher levels of DUP, we fitted those models also after log-transformation of DUP to control.
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Table 2. Socio-demographic and clinical characteristics of completers and non-completers.
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Non-completers (n ⫽ 63) Gender (%/n) Female Male Age (mean/s) Schooling years (mean/s) DUP in months (mean/s) Marital status (%/n) Divorced Married Remarried Single Widowed Drugs used (%/n) Aripiprazole Olanzapine Risperidone Drug switch (%/n) No change Aripiprazole Olanzapine Risperidone
Completers (n ⫽ 38)
Combined (n ⫽ 101)
Test statistics χ2 ⫽ 1.1; P ⫽ 0.29
56% (35) 44% (28) 26.7 (6.8) 13.1 (2.7) 9.8 (10.8)
45% (17) 55% (21) 25.9 (7.3) 12.2 (3.5) 9.8 (10.6)
51% (52) 49% (49) 26.4 (7.0) 12.8 (3.1) 9.8 (10.7)
6% (4) 16% (10) 0 % (0) 76% (48) 2 % (1)
8% (3) 21% (8) 3 % (1) 68% (26) 0 % (0)
7% (7) 18% (18) 1% (1) 73% (74) 1 % (1)
32% (20) 30% (19) 38% (24)
37% (14) 37% (14) 26% (10)
34% (34) 33% (33) 34% (33)
F ⫽ 0.52; P ⫽ 0.47 F ⫽ 2; P ⫽ 0.16 F ⫽ 0.06; P ⫽ 0.80 χ2 ⫽ 2.9; P ⫽ 0.58
χ2 ⫽ 1.5; P ⫽ 0.48
χ2 ⫽ 0.16; P ⫽ 0.98 62% (39) 6% (4) 25% (16) 6% (4)
63% (24) 5 % (2) 24% (9) 8% (3)
62% (63) 6% (6) 25% (25) 7% (7)
s, standard deviation; DUP, duration of untreated psychosis.
Results
Effect of DUP on cognitive and social functioning
Demographics and clinical characteristics
Table 4 shows the effect estimates of DUP on outcomes. For all outcomes, the omnibus likelihood
The demographic and clinical comparisons of all participants (completers and non-completers) are presented in Table 2. As can be seen, there were no significant differences between those who abandoned the study over the course of 1 year and those who continued (all P-values ⬎ 0.05). The main reasons for our non-completers were that some were no longer willing to be part of the study, had lost interest in the test, found the tests difficult or were unable to come for follow-up assessments. Some patients were probably experiencing marked social dysfunction and hence were unable to comprehend and fulfill the given tasks. The mean raw scores for completers (n ⫽ 38) in each cognitive domain and social function tests are displayed in Table 3.
Longitudinal course of cognitive and social functioning We found a significant impairment of about 1 ⫻ standard deviation in verbal learning and memory, and about half a standard deviation in executive functioning at the 6-month and 1-year follow-up compared with baseline. Motor speed was significantly lower at 1 year while working memory was slightly increased at the 1-year follow-up. In all other cognitive tests, no significant change was observed (Fig. 1). On the other hand, we found a stable pattern of increasing social functioning over the course of 1 year and a difference between baseline and the 1-year follow-up of about 2 ⫻ standard deviations.
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Table 3. Raw mean (standard deviation, s) scores of completers of cognitive and social function tests.
Tests Working memory PASAT Spatial span Processing speed Digit symbol Symbol search Trail A Executive function Color Trail line 2 Verbal learning/memory HVLT total learning HVLT delayed recall Visual memory BVMT total learning BVMT delayed recall Motor speed GP Dominant hand GP non-dominant hand PSP
Baseline, mean (s), n ⫽ 38
6-month, mean (s), n ⫽ 38
1-year, mean (s), n ⫽ 38
33.9 (9.8) 16.6 (3.7)
37.3 (8.9) 16.4 (2.5)
40.0 (9.5) 16.0 (2.8)
60.5 (14.5) 28.0 (9.0) 44.8 (18.2)
62.8 (16.5) 29.7 (10.8) 39.2 (16.9)
67.7 (13.9) 31.0 (11.0) 35.0 (13.8)
112.8 (49.1)
91.8 (30.5)
83.5 (28.1)
23.8 (4.6) 7.7 (2.2)
19.9 (5.3) 5.9 (2.5)
19.1 (5.6) 6.0 (2.7)
21.8 (7.1) 9.0 (3.1)
21.6 (7.0) 8.6 (2.7)
23.4 (7.8) 8.8 (3.2)
80.6 (17.7) 97.5 (44.1) 36.7 (15.6)
77.5 (21.6) 93.1 (37.9) 53.4 (16.8)
74.1 (16.4) 84.0 (17.4) 67.1 (10.9)
PASAT, Paced Addition Serial Addition Test; HVLT, Hopkins Verbal Learning Test, Revised; BVMT, Brief Visuospatial Memory Test, Revised; GP, Grooved Pegboard Test; PSP, Personal and Social Performance scale. NORD J PSYCHIATRY·EARLY ONLINE·2015
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Fig. 1. The longitudinal course of cognitive function.
ratio test revealed that inclusion of DUP in the statistical model did not result in an increased fit, for neither cognitive nor social functioning. However, effect estimates of an additional month of DUP ranged between ⫺ 0.03 and 0.02, which seemed small at first sight. Although statistically non-significant, clinically relevant effects cannot be ruled out due to small sample size. Sensitivity analysis with log-transformed DUP did not change this picture. NORD J PSYCHIATRY·EARLY ONLINE·2015
Discussion The aims of this study were to examine the effects of time and DUP on cognitive and social functioning. The main findings indicate that over time: 1) there is significant deterioration in verbal learning and memory and executive function; 2) a general worsening in performance of motor speed and a minor increase in performance in working memory; and 3) social function improves over time.
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Table 4. Effect of duration of untreated psychosis (DUP) on cognitive and social functions.
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Baseline
Effect of DUP Working memory Processing speed Executive function Verbal learning/memory Visual memory Motor speed PSP Effect of log DUP Working memory Processing speed Executive function Verbal learning/memory Visual memory Motor speed PSP
6-month
1-year
Overall test
Effect estimate
P-value
Effect estimate
P-value
Effect estimate
P-value
P-value
⫺ 0.01 0.01 0.02 0.01 0.00 ⫺ 0.01 ⫺ 0.01
0.564 0.306 0.079 0.531 0.815 0.221 0.494
⫺ 0.01 ⫺ 0.02 0.01 0.01 0.00 0.01 ⫺ 0.03
0.233 0.051 0.302 0.430 0.879 0.454 0.038
⫺ 0.02 ⫺ 0.01 0.01 ⫺ 0.01 ⫺ 0.01 0.00 ⫺ 0.01
0.072 0.517 0.262 0.519 0.324 0.707 0.409
0.205 0.053 0.330 0.266 0.521 0.193 0.202
⫺ 0.07 0.00 0.03 0.00 ⫺ 0.01 ⫺ 0.14 0.00
0.482 0.999 0.721 0.986 0.923 0.195 0.994
⫺ 0.12 ⫺ 0.18 0.11 0.09 ⫺ 0.04 0.00 ⫺ 0.20
0.227 0.037 0.227 0.513 0.765 0.990 0.109
⫺ 0.16 ⫺ 0.09 0.09 ⫺ 0.12 ⫺ 0.04 ⫺ 0.04 ⫺ 0.11
0.112 0.263 0.348 0.391 0.779 0.722 0.385
0.360 0.129 0.595 0.307 0.987 0.491 0.347
PSP, Personal and Social Performance scale.
Meanwhile, DUP did not share any relationship with cognitive or social function but seemed to exert a small yet clinically non-negligible effect.
Effect of time on cognitive function Cognitive deficits are common in schizophrenia and are even deemed core features (37, 38). We found that longitudinal assessment of cognitive function had no significant differences over time except in verbal learning, and memory and executive function. Our findings confirm that even in Chinese FES verbal memory is affected (39– 41). Though Rund et al. (42) claimed that cognitive deficits were stable in first-episode psychosis patients, others have found impairments in other domains such as executive function (19, 41, 43, 44). We believe that the general decrease in motor speed could be partially related to the effect of antipsychotics and we do not exclude the possibility that since this test was the last in the battery of tests, patients had lost interest in the process.
Effect of time on social function The longitudinal course of social function improved over 1 year. There was a considerable increase in PSP scores from baseline to 1 year in all patients, which could be attributed to the effectiveness of the antipsychotics used. Similar improvements were noted by Popolo et al. (45).
Effect of DUP on cognitive function We found that DUP did not result into any increased model fit with cognitive function. Similar findings were obtained after logarithmic transformation of the DUP. Our findings correlate with those of Ayres et al. (16),
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Goldberg et al. (17) and Malla et al. (18). However, there are some studies reporting a longer DUP leading to impaired performance on different cognitive domains such as Verbal IQ and verbal working memory (21), attention (19) and visual memory (23). Differences in findings might be due to different sets of cognitive tests used and different mean DUP. Despite growing evidence that cognitive deficits are present long before the onset of schizophrenia (46, 47) and data supporting neurodevelopmental hypothesis for cognitive impairment in schizophrenia (48, 49), the toxic effect of psychosis cannot be completely dismissed (18). In our study, the small effect estimate of the DUP effect seems to illustrate this viewpoint.
Effect of DUP on social function Deterioration in social function in FES occurs after the onset of disease and shows mild improvement over time (50). We found that there was no increased model fit between DUP and social function. Some studies reported that a longer DUP led to a deterioration in social function (26, 28, 29, 32). However, it should be noted that these studies used the Global Assessment of Functioning (GAF) or the Social Function Scale (SFS) scale for measuring social function and had a longer median DUP and follow-ups. In a systematic review, Marshall et al. (27), found a modest association between length of DUP and functional outcome, and it was noted that outcome was independent of premorbid adjustment.
Limitations Despite our homogeneous sample of FES, limitations that came up were: 1) missing data for cognitive assessments NORD J PSYCHIATRY·EARLY ONLINE·2015
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contributing to increased Type II statistical error; 2) the potential effects of antipsychotics interfering with cognitive and social functioning were not investigated. However, recent findings from the Clinical Antipsychotics Trial of Intervention Effectiveness (CATIE) trial showed no significant differences in neurocognitive functioning in response to medications (51); 3) DUP was assessed through structured clinical interview and not through use of a scale.
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Conclusions Chinese FES patients are impaired in verbal learning and memory and executive function over the course of 1 year. Social function improves significantly with the effect of antipsychotics; hence, early detection and regular medication are important for improving functional outcome. DUP was not found to be associated with cognitive or social deterioration in Chinese FES.
Role of funding source The “di shi yi wu” or National Five-year plan was supported by the National Key Project of Scientific and Technical Supporting Programs and funded by the Ministry of Science & Technology of China (No. 2007BAI17B04). Acknowledgment—The authors wish to extend their gratitude to Dr. Rainer Leonhart of the University of Freiburg for his assistance in statistical analysis.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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