This article was downloaded by: [University of Otago] On: 30 December 2014, At: 10:19 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Child & Adolescent Mental Health Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/rcmh20
Cannabis use and family history in adolescent first episode psychosis in Durban, South Africa a
a
Saeeda Paruk , Jonathan K Burns & Rochelle Caplan
b
a
Nelson R Mandela School of Medicine , University of KwaZulu Natal , South Africa b
Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine , University of California , Los Angeles (UCLA) , USA Published online: 31 May 2013.
To cite this article: Saeeda Paruk , Jonathan K Burns & Rochelle Caplan (2013) Cannabis use and family history in adolescent first episode psychosis in Durban, South Africa, Journal of Child & Adolescent Mental Health, 25:1, 61-68, DOI: 10.2989/17280583.2013.767264 To link to this article: http://dx.doi.org/10.2989/17280583.2013.767264
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms
Downloaded by [University of Otago] at 10:19 30 December 2014
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Journal of Child and Adolescent Mental Health 2013, 25(1): 61–68 Printed in South Africa — All rights reserved
Copyright © NISC Pty Ltd
JOURNAL OF C H I L D & A D O LES C EN T M EN T A L H EA L T H ISSN 1728-0583 EISSN 1728-0591 http://dx.doi.org/10.2989/17280583.2013.767264
Research Paper Cannabis use and family history in adolescent first episode psychosis in Durban, South Africa Saeeda Paruk1*, Jonathan K Burns1 and Rochelle Caplan2 Nelson R Mandela School of Medicine, University of KwaZulu Natal, South Africa Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles (UCLA), USA *Corresponding author, email: [email protected]/[email protected]
Downloaded by [University of Otago] at 10:19 30 December 2014
1
2
Objectives: To investigate the clinical correlates of cannabis use in adolescents with first episode psychosis (FEP). Methods: Inpatient psychiatric records provided demographic, lifetime cannabis use, family history of mental illness, and clinical data on 45 FEP adolescents, aged 12–18 years, admitted to a psychiatric unit in Durban, KwaZulu-Natal, South Africa, over a 2-year period. Results: Thirty-one (68.8%) of the 45 FEP adolescents reported a history of lifetime cannabis use. The age of FEP presentation and pre-diagnosis symptom duration was not significantly different in cannabis users versus non cannabis users. Of the 15/43 (34.8%) FEP patients with family history of mental illness, 10 had a history of cannabis use. The 26 (57.8%) schizophrenia spectrum disorder patients did not differ significantly from the 19 (42.2%) with other psychoses in terms of cannabis use and family history of mental illness. They were, however, significantly younger at age of presentation and had a significantly longer duration of pre-diagnosis symptoms. Conclusions: These preliminary findings suggest a high prevalence of cannabis use in adolescents with FEP and highlight the public health concern of addressing substance abuse in the adolescent population.
Introduction Cannabis is the most commonly used illicit substance worldwide and there is an increased incidence of cannabis use in individuals with mental illness (van Os et al. 2002, Brink et al. 2003, United Nations Office on Drugs and Crime 2008, Koen, Jonathan and Niehaus 2009). Cannabis use is considered a risk factor for developing psychosis and comorbid use in first episode psychosis (FEP) predicts poorer outcome (van Os et al. 2002, Arseneault et al. 2004, Moore et al. 2007, Leeson et al. 2011). Cannabis and demographic variables in psychosis In a review of epidemiological studies of cannabis and adult psychosis, Arseneault et al. (2004) concluded that cannabis confers a twofold increase in relative risk for the development of schizophrenia later in adult life. In the Dunedin Multidisciplinary Health and Development study, individuals using cannabis at ages 15 and 18 had higher rates of psychotic illness at age 26 than non-users; and cannabis use by age 15 was associated with increased likelihood of a diagnosis of schizophreniform disorder at age 26 (Silva and Stanton 1996). More recently, Estrada et al. (2011) reported that age of first cannabis use seems to modify age of onset of schizophrenic spectrum disorders and other psychiatric disorders; and that the use of cannabis before age 18 is associated Journal of Child & Adolescent Mental Health is co-published by NISC (Pty) Ltd and Routledge, Taylor & Francis Group
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Paruk, Burns and Caplan
Downloaded by [University of Otago] at 10:19 30 December 2014
with increased risk of psychosis compared to initiating cannabis in adulthood. Cannabis and clinical variables of psychosis Brink et al. (2003) concluded that there was a high comorbidity between substance abuse and first episode psychosis in South Africa among males and that these individuals aged 15–55 years with substance abuse present with FEP at a younger age. Burns, Jhazbhai and Emsley (2010) also reported increased prevalence of cannabis use and a slight male preponderance in adults with first episode psychotic disorders in KwaZulu-Natal. In a study of 16–60-year-old schizophrenia and schizophrenia spectrum patients with cannabis use, Leeson et al. (2011) reported a correlation between cannabis use and age of presentation and argued that early age of onset of psychosis in cannabis users reflects a toxic effect of cannabis rather than this being a feature of the underlying psychotic illness. The association between cannabis use and duration of symptoms before treatment has also been of interest as it has implications for prognosis (Jeppesen et al. 2008, Farooq et al. 2009). Leeson et al. (2011) and Burns et al. (2010) have reported no association between cannabis use and duration of symptoms in adult samples of first episode psychosis. A recent systematic review found that while most studies reported shorter duration of untreated psychosis (DUP) in cannabis-using patients, meta-analysis did not detect a significant relationship between DUP and cannabis use (Burns 2012). Interestingly, in contrast to adult studies (Leeson et al. 2011), Schimmelmann et al. (2011) reported that baseline cannabis use was associated with an older age of onset and longer duration of untreated psychosis in an adolescent early onset psychosis study. Their explanation was that in adolescents (versus adults), younger pre-psychotic adolescents were less likely to access cannabis than older adolescents in keeping with the general increase in cannabis use with increasing age in the general adolescent population and that this counteracted the potential neurotoxic effect of cannabis causing early onset of symptoms in their sample. Family history of mental illness Faridi et al. (2009) concluded that diverse psychopathology is common in families of FEP patients and this may imply a generalised vulnerability to psychiatric disorders in general in such families compared to a vulnerability to psychosis more specifically. Gregg, Barrowclough and Haddock (2007) suggest that substance use and schizophrenia share a common genetic vulnerability; however the exact genetic factors are yet to be identified. Early onset schizophrenia is also associated with high familial risk, and the risk of cannabis related psychosis is higher in first-degree relatives of FEP probands (Estrada et al. 2011). In South Africa, Koen et al. (2009) demonstrated that FEP patients with cannabis use had a lower mean age of presentation of onset of illness and hypothesized that cannabis use increases the vulnerability to first episode psychosis in in genetically vulnerable individuals (Koen et al. 2009) . The Koen et al. (2009) hypothesis is supported by the association between COMT Val158Met polymorphism and cannabis use in the early emergence of psychosis in young people (Estrada et al. 2011); and by the association between a positive family history of schizophrenia and increased sensitivity to cannabis (McGuire et al. 1995). This study therefore examined the association of both cannabis use and positive family history of mental illness with clinical correlates in first episode psychosis in adolescents in the South African setting. We predicted that cannabis use in adolescent FEP would be associated with a family history of mental illness (FHMI). Table 1 summarises the data from recent local and international studies which included cannabis use, age of onset and DUP in adolescent FEP subjects. Objectives The aim of the study was to describe the profile of adolescents presenting with first episode psychosis to a psychiatric unit and the association with life-time cannabis use and family history of mental illness.
Journal of Child and Adolescent Mental Health 2013, 25(1): 61–68
63
Table 1: FEP studies examining association between cannabis use/family history of psychosis and age of onset and DUP.
Downloaded by [University of Otago] at 10:19 30 December 2014
Study/author
FEP patient Age group sample (years) size (N)
Cannabis use Lifetime cannabis use, 29.1% Lifetime cannabis use, 45.0%
Age of onset and cannabis use
DUP and cannabis use
Family history of mental illness
Not studied
Not studied
Not studied
Age of first cannabis use correlated with age of onset
Not studied
No difference in distribution of COMT Val 158 Met and cannabis Not studied
CAFEPS; Baeza et al. (2009) Estrada et al. (2011)
110
9–17
157
Mean age = 17.1 (SD 3.60)
Sevy et al. (2010)
49
16–40
74% had Earlier age of cannabis use onset in male disorder (CUD) CUD patients before psychosis
No statistical difference
Leeson et al. (2011)
99
16–60
69% of sample Younger age at had cannabis prodrome and exposure and age of onset 71% males used cannabis
No statistical difference
Brink et al. (2003) (South Africa)
33
Mean age = 29.25 years
Cannabis most commonly used substance (p = 0.03)
Burns et al. (2010) (South Africa)
54
EPPIC study; Schimmelmann et al. (2010)
99
16–45 and current average cannabis use age of 25 = 35% years, 8 months 14–18 65.7% lifetime cannabis use
Younger age Not available of onset of psychosis in substance users No association
Shorter DUP (0.026)
No association
Longer DUP (p = 0.027)
No association between age of onset and family history of psychosis Not available
A post hoc exploratory analysis was also performed on the association between age of presentation and duration of symptoms pre-treatment and: 1) lifetime cannabis exposure; 2) family history of mental illness; and 3) diagnostic category. Methods Subjects Forty-five FEP adolescents were identified from a retrospective record review of all adolescent admissions over a two-year period at a psychiatric unit in Durban, KwaZulu-Natal, South Africa. The study included all adolescents in the age range 12 to 18 years who presented with psychotic symptoms requiring admission and excluded those managed as outpatients. Procedures A child psychiatrist extracted the following data from the patients’ hospital files: demographic data (age, gender, religion, ethnicity, language and educational level); risk factors (lifetime substance
64
Paruk, Burns and Caplan
use, family history of mental illness, medical history, past psychiatric history, forensic history, and any documented psychosocial stressors); the DSM-IV-TR diagnosis; and the duration of psychotic symptoms reported by the patient or caregiver. All DSM-V-TR diagnoses of schizophreniform disorder, schizophrenia and schizoaffective disorder were categorised as ‘schizophrenia-spectrum psychosis’, while those with substance-induced psychotic disorders, psychosis due to general medical condition, mood disorders with psychotic features and psychotic disorder not otherwise specified were categorised as ‘other psychoses’.
Downloaded by [University of Otago] at 10:19 30 December 2014
Definitions Cannabis use was defined as a positive report of lifetime cannabis exposure before seeking treatment. Family history of mental illness included first and second degree relatives, and was based on information recorded in the medical records from patient and family members during the clinical assessment. Family history of psychosis specifically could not be accurately assessed in all cases as the data were unavailable either due to limitations in record keeping or because families often do not know the precise diagnoses. Duration of symptoms pre-treatment refers to the period in weeks of the first appearance of positive and/or negative symptoms noted by patient and/or care giver and the initiation of treatment in hospital. Duration of untreated psychosis in the literature generally refers to the period in weeks between the first appearance of positive psychotic symptoms and treatment initiation and while the duration of symptoms pre-treatment is not as specific, it still provides insight into the period interval before patients seek/receive treatment. Age of presentation was defined in years as the age at treatment initiation. Age at first hospitalisation was also age of presentation, as all the adolescents were admitted at treatment initiation. Ethics approval was obtained from the Biomedical Research Ethics Committee at the University of KwaZulu-Natal, the provincial department of health and the hospital. Statistical analysis Data were analysed using SPSS version 15.0 (SPSS Inc.; Chicago, Illinois, USA) package and a P value of
Journal of Child & Adolescent Mental Health Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/rcmh20
Cannabis use and family history in adolescent first episode psychosis in Durban, South Africa a
a
Saeeda Paruk , Jonathan K Burns & Rochelle Caplan
b
a
Nelson R Mandela School of Medicine , University of KwaZulu Natal , South Africa b
Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine , University of California , Los Angeles (UCLA) , USA Published online: 31 May 2013.
To cite this article: Saeeda Paruk , Jonathan K Burns & Rochelle Caplan (2013) Cannabis use and family history in adolescent first episode psychosis in Durban, South Africa, Journal of Child & Adolescent Mental Health, 25:1, 61-68, DOI: 10.2989/17280583.2013.767264 To link to this article: http://dx.doi.org/10.2989/17280583.2013.767264
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms
Downloaded by [University of Otago] at 10:19 30 December 2014
& Conditions of access and use can be found at http://www.tandfonline.com/page/ terms-and-conditions
Journal of Child and Adolescent Mental Health 2013, 25(1): 61–68 Printed in South Africa — All rights reserved
Copyright © NISC Pty Ltd
JOURNAL OF C H I L D & A D O LES C EN T M EN T A L H EA L T H ISSN 1728-0583 EISSN 1728-0591 http://dx.doi.org/10.2989/17280583.2013.767264
Research Paper Cannabis use and family history in adolescent first episode psychosis in Durban, South Africa Saeeda Paruk1*, Jonathan K Burns1 and Rochelle Caplan2 Nelson R Mandela School of Medicine, University of KwaZulu Natal, South Africa Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles (UCLA), USA *Corresponding author, email: [email protected]/[email protected]
Downloaded by [University of Otago] at 10:19 30 December 2014
1
2
Objectives: To investigate the clinical correlates of cannabis use in adolescents with first episode psychosis (FEP). Methods: Inpatient psychiatric records provided demographic, lifetime cannabis use, family history of mental illness, and clinical data on 45 FEP adolescents, aged 12–18 years, admitted to a psychiatric unit in Durban, KwaZulu-Natal, South Africa, over a 2-year period. Results: Thirty-one (68.8%) of the 45 FEP adolescents reported a history of lifetime cannabis use. The age of FEP presentation and pre-diagnosis symptom duration was not significantly different in cannabis users versus non cannabis users. Of the 15/43 (34.8%) FEP patients with family history of mental illness, 10 had a history of cannabis use. The 26 (57.8%) schizophrenia spectrum disorder patients did not differ significantly from the 19 (42.2%) with other psychoses in terms of cannabis use and family history of mental illness. They were, however, significantly younger at age of presentation and had a significantly longer duration of pre-diagnosis symptoms. Conclusions: These preliminary findings suggest a high prevalence of cannabis use in adolescents with FEP and highlight the public health concern of addressing substance abuse in the adolescent population.
Introduction Cannabis is the most commonly used illicit substance worldwide and there is an increased incidence of cannabis use in individuals with mental illness (van Os et al. 2002, Brink et al. 2003, United Nations Office on Drugs and Crime 2008, Koen, Jonathan and Niehaus 2009). Cannabis use is considered a risk factor for developing psychosis and comorbid use in first episode psychosis (FEP) predicts poorer outcome (van Os et al. 2002, Arseneault et al. 2004, Moore et al. 2007, Leeson et al. 2011). Cannabis and demographic variables in psychosis In a review of epidemiological studies of cannabis and adult psychosis, Arseneault et al. (2004) concluded that cannabis confers a twofold increase in relative risk for the development of schizophrenia later in adult life. In the Dunedin Multidisciplinary Health and Development study, individuals using cannabis at ages 15 and 18 had higher rates of psychotic illness at age 26 than non-users; and cannabis use by age 15 was associated with increased likelihood of a diagnosis of schizophreniform disorder at age 26 (Silva and Stanton 1996). More recently, Estrada et al. (2011) reported that age of first cannabis use seems to modify age of onset of schizophrenic spectrum disorders and other psychiatric disorders; and that the use of cannabis before age 18 is associated Journal of Child & Adolescent Mental Health is co-published by NISC (Pty) Ltd and Routledge, Taylor & Francis Group
62
Paruk, Burns and Caplan
Downloaded by [University of Otago] at 10:19 30 December 2014
with increased risk of psychosis compared to initiating cannabis in adulthood. Cannabis and clinical variables of psychosis Brink et al. (2003) concluded that there was a high comorbidity between substance abuse and first episode psychosis in South Africa among males and that these individuals aged 15–55 years with substance abuse present with FEP at a younger age. Burns, Jhazbhai and Emsley (2010) also reported increased prevalence of cannabis use and a slight male preponderance in adults with first episode psychotic disorders in KwaZulu-Natal. In a study of 16–60-year-old schizophrenia and schizophrenia spectrum patients with cannabis use, Leeson et al. (2011) reported a correlation between cannabis use and age of presentation and argued that early age of onset of psychosis in cannabis users reflects a toxic effect of cannabis rather than this being a feature of the underlying psychotic illness. The association between cannabis use and duration of symptoms before treatment has also been of interest as it has implications for prognosis (Jeppesen et al. 2008, Farooq et al. 2009). Leeson et al. (2011) and Burns et al. (2010) have reported no association between cannabis use and duration of symptoms in adult samples of first episode psychosis. A recent systematic review found that while most studies reported shorter duration of untreated psychosis (DUP) in cannabis-using patients, meta-analysis did not detect a significant relationship between DUP and cannabis use (Burns 2012). Interestingly, in contrast to adult studies (Leeson et al. 2011), Schimmelmann et al. (2011) reported that baseline cannabis use was associated with an older age of onset and longer duration of untreated psychosis in an adolescent early onset psychosis study. Their explanation was that in adolescents (versus adults), younger pre-psychotic adolescents were less likely to access cannabis than older adolescents in keeping with the general increase in cannabis use with increasing age in the general adolescent population and that this counteracted the potential neurotoxic effect of cannabis causing early onset of symptoms in their sample. Family history of mental illness Faridi et al. (2009) concluded that diverse psychopathology is common in families of FEP patients and this may imply a generalised vulnerability to psychiatric disorders in general in such families compared to a vulnerability to psychosis more specifically. Gregg, Barrowclough and Haddock (2007) suggest that substance use and schizophrenia share a common genetic vulnerability; however the exact genetic factors are yet to be identified. Early onset schizophrenia is also associated with high familial risk, and the risk of cannabis related psychosis is higher in first-degree relatives of FEP probands (Estrada et al. 2011). In South Africa, Koen et al. (2009) demonstrated that FEP patients with cannabis use had a lower mean age of presentation of onset of illness and hypothesized that cannabis use increases the vulnerability to first episode psychosis in in genetically vulnerable individuals (Koen et al. 2009) . The Koen et al. (2009) hypothesis is supported by the association between COMT Val158Met polymorphism and cannabis use in the early emergence of psychosis in young people (Estrada et al. 2011); and by the association between a positive family history of schizophrenia and increased sensitivity to cannabis (McGuire et al. 1995). This study therefore examined the association of both cannabis use and positive family history of mental illness with clinical correlates in first episode psychosis in adolescents in the South African setting. We predicted that cannabis use in adolescent FEP would be associated with a family history of mental illness (FHMI). Table 1 summarises the data from recent local and international studies which included cannabis use, age of onset and DUP in adolescent FEP subjects. Objectives The aim of the study was to describe the profile of adolescents presenting with first episode psychosis to a psychiatric unit and the association with life-time cannabis use and family history of mental illness.
Journal of Child and Adolescent Mental Health 2013, 25(1): 61–68
63
Table 1: FEP studies examining association between cannabis use/family history of psychosis and age of onset and DUP.
Downloaded by [University of Otago] at 10:19 30 December 2014
Study/author
FEP patient Age group sample (years) size (N)
Cannabis use Lifetime cannabis use, 29.1% Lifetime cannabis use, 45.0%
Age of onset and cannabis use
DUP and cannabis use
Family history of mental illness
Not studied
Not studied
Not studied
Age of first cannabis use correlated with age of onset
Not studied
No difference in distribution of COMT Val 158 Met and cannabis Not studied
CAFEPS; Baeza et al. (2009) Estrada et al. (2011)
110
9–17
157
Mean age = 17.1 (SD 3.60)
Sevy et al. (2010)
49
16–40
74% had Earlier age of cannabis use onset in male disorder (CUD) CUD patients before psychosis
No statistical difference
Leeson et al. (2011)
99
16–60
69% of sample Younger age at had cannabis prodrome and exposure and age of onset 71% males used cannabis
No statistical difference
Brink et al. (2003) (South Africa)
33
Mean age = 29.25 years
Cannabis most commonly used substance (p = 0.03)
Burns et al. (2010) (South Africa)
54
EPPIC study; Schimmelmann et al. (2010)
99
16–45 and current average cannabis use age of 25 = 35% years, 8 months 14–18 65.7% lifetime cannabis use
Younger age Not available of onset of psychosis in substance users No association
Shorter DUP (0.026)
No association
Longer DUP (p = 0.027)
No association between age of onset and family history of psychosis Not available
A post hoc exploratory analysis was also performed on the association between age of presentation and duration of symptoms pre-treatment and: 1) lifetime cannabis exposure; 2) family history of mental illness; and 3) diagnostic category. Methods Subjects Forty-five FEP adolescents were identified from a retrospective record review of all adolescent admissions over a two-year period at a psychiatric unit in Durban, KwaZulu-Natal, South Africa. The study included all adolescents in the age range 12 to 18 years who presented with psychotic symptoms requiring admission and excluded those managed as outpatients. Procedures A child psychiatrist extracted the following data from the patients’ hospital files: demographic data (age, gender, religion, ethnicity, language and educational level); risk factors (lifetime substance
64
Paruk, Burns and Caplan
use, family history of mental illness, medical history, past psychiatric history, forensic history, and any documented psychosocial stressors); the DSM-IV-TR diagnosis; and the duration of psychotic symptoms reported by the patient or caregiver. All DSM-V-TR diagnoses of schizophreniform disorder, schizophrenia and schizoaffective disorder were categorised as ‘schizophrenia-spectrum psychosis’, while those with substance-induced psychotic disorders, psychosis due to general medical condition, mood disorders with psychotic features and psychotic disorder not otherwise specified were categorised as ‘other psychoses’.
Downloaded by [University of Otago] at 10:19 30 December 2014
Definitions Cannabis use was defined as a positive report of lifetime cannabis exposure before seeking treatment. Family history of mental illness included first and second degree relatives, and was based on information recorded in the medical records from patient and family members during the clinical assessment. Family history of psychosis specifically could not be accurately assessed in all cases as the data were unavailable either due to limitations in record keeping or because families often do not know the precise diagnoses. Duration of symptoms pre-treatment refers to the period in weeks of the first appearance of positive and/or negative symptoms noted by patient and/or care giver and the initiation of treatment in hospital. Duration of untreated psychosis in the literature generally refers to the period in weeks between the first appearance of positive psychotic symptoms and treatment initiation and while the duration of symptoms pre-treatment is not as specific, it still provides insight into the period interval before patients seek/receive treatment. Age of presentation was defined in years as the age at treatment initiation. Age at first hospitalisation was also age of presentation, as all the adolescents were admitted at treatment initiation. Ethics approval was obtained from the Biomedical Research Ethics Committee at the University of KwaZulu-Natal, the provincial department of health and the hospital. Statistical analysis Data were analysed using SPSS version 15.0 (SPSS Inc.; Chicago, Illinois, USA) package and a P value of
