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Duration of untreated psychosis in adolescents: Ethnic differences and clinical profiles
Schizophrenia Research, 2-3, 150, pages 526 - 532
Duration of Untreated Psychosis (DUP) is an important measure associated with outcome of psychosis. This first study in the UK compared DUP between adolescent and adult-onset individuals and explored whether the adolescent-onset group showed variations in DUP that could be accounted for by sociodemographic and selected risk factors.
This naturalistic cohort study included 940 new first-episode psychosis cases aged 14–35 years (136 adolescent-onset versus 804 adult-onset psychotic individuals) referred to nine Early Intervention Services for Psychosis in London (2003–2009). Sociodemographic characteristics, age of onset, family history of mental illness, duration of untreated psychosis, suicidality and substance use information were collected at entry to the services.
Adolescents presented with significantly greater median DUP (179 days) than adults (81 days, p = 0.005). Large differences in DUP were found amongst adolescent ethnic groups (median DUP: White: 454 days; Black: 103 days; Asian and mixed: 28.5 days). In addition, younger age of onset and higher lifetime cannabis use were associated with longer treatment delay amongst adolescents.
This study of DUP in adolescent-onset psychosis found it to be approximately twice the length of DUP amongst adults. For the adolescent White sub-group, DUP was far greater than the UK Department of Health target (< 3 months). Both the high rates of lifetime cannabis use and the lower age of onset might explain the long DUP in this ethnic group. Physicians need to be particularly vigilant about identifying and managing early psychosis in adolescents.
Keywords: Adolescence, First episode psychosis, Duration of untreated psychosis, Ethnicity, Cannabis, Age of onset.
Duration of Untreated Psychosis (DUP), defined as the time between the onset of psychotic symptoms continuous with the presenting episode and the onset of continuous antipsychotic medication (30 days or less if symptoms remitted) ( Norman and Malla, 2001 ), has become established as an important measure associated with psychosis outcome. Two systematic reviews (Marshall et al, 2005 and Perkins et al, 2005) reported that longer DUP in First Episode Psychosis (FEP), including the broad range of full-blown psychotic conditions (Verdoux et al, 2001 and Melle et al, 2004), is associated with more severe negative symptoms at treatment initiation, and more severe (negative, positive and depression/anxiety) symptoms, poorer functioning and less likelihood to achieve remission at 6, 12 and 24 months. Conversely, shorter DUP was associated with greater treatment responsiveness reflected by greater reduction in psychotic, negative, and global psychopathology.
Although a clear time cut-off has not been established, previous studies have identified that outcomes were significantly worse when DUP exceeded either 3 or 6 months (Carbone et al, 1999, Harrigan et al, 2003, and Melle et al, 2004). In 2003, the UK Department of Health set a national target to reduce DUP to a service median of 3 months and an individual maximum of 6 months ( Department-of-Health, 2003 ).
Previous studies suggest that DUP is two to three times greater for adolescents than for adults, but the reasons for this are unclear (Ballageer et al, 2005, White et al, 2006, Schimmelmann et al, 2007, and Joa et al, 2009). The current study aimed to explore whether the adolescent-onset group shows variations in DUP and what might account for these differences. We hypothesized that: (i) adolescent-onset psychotic individuals would show a significantly longer DUP than adult-onset individuals in a large pan-London naturalistic cohort, and (ii) ethnic and clinical characteristics would play a role shaping DUP amongst adolescents.
2.1. Study design and sample
In a naturalistic cross-sectional cohort study, the sample included patients referred to nine Early Intervention Services for Psychosis (EIS) in London (UK) between 2003 and 2009. These teams serve 13 of London's 33 boroughs including a population of 2.7 million. Inclusion criteria were new referrals of individuals: (i) aged between 14 and 35 years, (ii) who had presented for the first time within the last year to mental health services with more than a week of unremitting frank psychotic symptoms, and (iii) who had less than 6 months of antipsychotic treatment for psychosis. Further details on the sample are available (Fisher et al, 2008 and Ghali et al, 2012).
Detailed sampling procedures for the current study are illustrated in Fig. 1 . Out of the total of 1363 referred individuals, 17 of them did not fulfill criteria for FEP, and another 406 did not have data on age of onset of psychosis. Consequently, this study included a sample of 940 FEP individuals (136 adolescent-onset versus 804 adult-onset psychotic individuals). Included (n = 940) and non-included (n = 406) samples of FEP did not show significant differences in either gender or ethnic distribution.
2.2. Data collection
Data were collected using MiData (minimum data-set) ( Fisher et al., 2008 ). This tool contains standardised measures chosen for the coverage of key areas, feasibility, brevity and established use within the literature for FEP patients. Experienced clinicians, mostly care coordinators, collected and entered the data following the completion of a comprehensive clinical assessment on entry into EIS and having had access to clinical records and collateral history. Multicentre ethical approval to merge anonymised MiData datasets was granted by the Wandsworth Research Ethics Committee.
2.3. Sociodemographic characteristics
Gender, country of birth and, where possible, that of their mother and father were routinely obtained at baseline. Based on this information, clinicians recorded Ethnicity largely in accordance with the 2001 Census of Population for England & Wales ( Office for National Statistics, 2001 ). Individuals were initially assigned to one of the 19 categories. For descriptive and analysis purposes, these were subsequently distilled to five ethnic groups (White, Black British, Other Black, Asian and Mixed people), and further reduced to three broad categories (White, Black, Asian and Mixed) excluding all other ethnic groups ( Ghali et al., 2012 ).
Family history of psychosis (including bipolar disorder) and that of any other psychiatric disorder in first-degree relatives were systematically collected. Additionally, a combined variable of Family history of any psychiatric disorder (coded as ‘1’ for either psychosis or any other psychiatric disorder versus ‘0’ for no psychiatric disorders) was created.
2.4. Clinical characteristics
- (a) The shortened version of the Nottingham Onset Schedule ( Singh et al., 2005 ) (NOS-DUP) is a standardised and reliable instrument for recording relatively precise time-points in emerging psychosis (i.e. the emergence of First Positive psychotic Symptoms (FPS) based on the Positive and Negative Syndrome Scale (PANSS) ( Kay et al., 1987 ) and transition into a psychotic episode). Clinicians achieved satisfactory inter-rater reliability with PANSS and NOS-DUP before completing the assessment. DUP was defined as a continuous variable based on the number of days between date of FPS, and the date of commencement of regular prescribed antipsychotic medication with adherence for at least 75% of the time during the subsequent month. Service-DUP was defined as a continuous variable based on the number of days between date of FPS and date of referral to EIS. Age of Onset was defined as the age of the individual (in years) at which there was clear evidence of the presence of an FPS (i.e. hallucinations, delusions and/or thought disorder, rated as 4 or more on the PANSS), and subsequently dichotomized into adolescent-onset (< age 18) versus adult-onset (≥ age 18) groups ( AACAP, 2001 ).
- (b) The Drake Substance Misuse Scale ( Drake et al., 1996 ) assesses the client's use of alcohol and numerous substances. Lifetime Cannabis Use was dichotomously defined as presence versus absence of any use of cannabis during the lifetime.
- (c) As part of the clinical risk assessment, Lifetime Suicidality was dichotomously rated as the presence versus absence of any incidents of suicide attempts in client’s lifetime.
2.5. Statistical analyses
Chi-square tests were applied for comparisons of categorical variables. The distributions of DUP, Service DUP and age of onset were significantly skewed and the non-parametric Mann–Whitney Test was applied for comparison between groups. The Kruskal–Wallis test with Bonferroni correction was used to compare DUP in the three ethnic groups. We used Spearman correlation to investigate DUP and age of onset. All variables revealing a significant influence on DUP within the adolescent group were included in a general linear model using analysis of covariance (ANCOVA). Interactions among the variables were explored. We obtained normally distributed residuals after removing 3 outliers, and assumptions were met.
3.1. Subject characteristics
The average age of onset of the included sample (n = 904 FEP) was 23 years. Fifteen percent of them (n = 136) presented with adolescent-onset psychosis whereas 85% (n = 804) experienced their FPS in adulthood. The majority (n = 59, 43.4%) of adolescents experienced their first psychotic symptom at age 17, 43 (31.6%) at age 16, 14 (10.3%) at age 15, 8 (5.9%) at age 14 and for 12 (8.8%) it commenced below age 13. Age groups did not show significant differences in gender, ethnicity, family history of psychosis or any psychiatric disorder, lifetime cannabis use or suicidality ( Table 1 ).
|Variable||Included sample n = 940||Adolescent onset (< age 18) n = 136||Adult onset (= > age 18) n = 804||Test statistics||p-value|
|n (mean, SD)||n (median, IQR)||n (median, IQR)|
|Age of onset||940 (23 yr, 5.0)||136 (16.9 yrs, 16.0–17.5)||804 (23.4 yrs, 20.4–27.2)||–||–|
|n (valid %)||n (valid %)||n (valid %)|
|Gender||X2 = 0.72||0.396|
|Male||604 (64.3%)||83 (61.0%)||521(64.8%)|
|Female||336 (35.7%)||53 (39.0%)||283 (35.2%)|
|Ethnicity (5 categories)||–||–|
|White (White British, Irish, Turkish, Greek and Others)||323 (34.4%)||45 (33.1%)||278 (34.6%)|
|Black British||59 (6.3%)||17 (12.5%)||42 (5.2%)|
|Other Black (Black Caribbean, Black African and Others)||336 (35.7%)||46 (33.8%)||290 (36.1%)|
|Asian (Indian, Pakistani, Bangladeshi, Chinese and Others)||113 (12.0%)||8 (5.9%)||105 (13.1%)|
|Mixed||109 (11.6%)||20 (14.7%)||89 (11.1%)|
|Ethnicity (3 broad categories)||X2 = 1.39||0.498|
|White (White British, Irish, Turkish, Greek and Others)||323 (34.4%)||45 (33.1%)||278 (34.6%)|
|Black (Black British, Black Caribbean, Black African and Black Others)||395 (42.0%)||63 (46.3%)||332 (41.3)|
|Asian and mixed (Indian, Pakistani, Chinese, Bangladeshi, Asian Others and Mixed)||222 (23.6%)||28 (20.6%)||194 (24.1%)|
|Family history of Psychosis||X2 = 1.92||0.166|
|No||643 (78.0%)||81 (72.9%)||562 (78.8%)|
|Yes||181 (22.0%)||30 (27.1%)||151 (21.2%)|
|Family history of any Psychiatric Disorder||X2 = 2.79||0.094|
|No||519 (62.9%)||62 (55.9%)||457 (64.1%)|
|Yes||305 (37.1%)||49 (44.1%)||256 (35.9%)|
|Lifetime Cannabis Use||X2 = 0.23||0.636|
|No||293 (44.5%)||38 (42.2%)||255 (44.9%)|
|Yes||365 (55.5%)||52 (57.8%)||313 (55.1%)|
|Lifetime Suicidality||X2 = 0.009||0.925|
|No||553 (80.1%)||75 (79.8%)||478 (80.2%)|
|Yes||137 (19.9%)||19 (20.2%)||118 (19.8%)|
|n (median, IQR)||n (median, IQR)||n (median, IQR)|
|Duration of Untreated Psychosis||845 (86 days,19–282)||118 (179 days,18–514.5)||727 (81 days,19–244)||U = 36,058.5||0.005|
|Service DUP||940 (135 days,39.3–372.0)||136 (346 days,105.5–721.3)||804 (120 days,37.0–311.3)||U = 37,238.5||0.000|
n = sample size; % = percentage; IQR = interquartile range; SD = standard deviation; Missing: Any missing value.
3.2. DUP comparison between age groups
The median DUP for the included sample (data available for n = 845) was 86 days (IQR: 19–282). The adolescent-onset group presented a significantly greater median DUP (179 days) than the adult-onset group (81 days), p = 0.005.
The median Service-DUP for the included sample (n = 940) was 135 days (IQR: 39.3–372.0). The same pattern was found for Service-DUP comparisons: the adolescent-onset group presented a significantly greater median Service-DUP (346 days) than the adult-onset group (120 days), p < 0.001 ( Fig. 2 ).
3.3. Determinants of DUP amongst adolescents
Individual hypothesis testing ( Table 2 ) showed that younger age of onset (R: − 0.348; p < 0.0001) and White ethnicity (X2 = 9.5; p = 0.009) were significantly associated with DUP amongst adolescents. After Bonferroni correction differences remained significant for the comparison of White versus Black ethnicity (p = 0.03) and White versus Asian and mixed ethnicity (p = 0.021). Marginal evidence of a difference in median DUP was found between lifetime cannabis users (275 days) versus nonusers (95 days) (p = 0.049). Neither gender nor family history of psychosis (or any psychiatric disorder), nor lifetime suicidality demonstrated a significant association with DUP amongst adolescents.
|Variable||Variable estimates||DUP estimates (in days)||Test statistics||p-value|
|Age of onset (n = 118)||16.9||16.0–17.5||179.0||18.0–514.5||rs: − 0.348||< 0.0001|
|n (valid %)||median||IQR|
|Gender (n = 118)||U = 1615.5||0.881|
|Ethnicity (3 broad categories) (n = 118)||X2 = 9.5||0.009|
|White||36 (30.5%)||345.5||99.3–985.3||U = 699.0||White vs Black: 0.03*|
|Black||56 (47.5%)||103.5||14.8–385.3||U = 280.0||White vs Asian: 0.021*|
|Asian and mixed||26 (22.0%)||36.5||6.8–327.8||U = 636.0||Black vs Asian: 1.000*|
|Family history of Psychosis (n = 96)||U = 904.0||0.590|
|Family history of any Psychiatric Disorder (n = 96)||U = 1124.5||0.886|
|Lifetime Cannabis Use (n = 76)||U = 522.0||0.049|
|Lifetime Suicidality (n = 81)||U = 480.0||0.323|
n = sample size; % = percentage; IQR = interquartile range; * = Bonferroni correction. DUP: Duration of Untreated Psychosis.
When age of onset, lifetime cannabis use and ethnicity were included together in a general linear model (n = 73; Table 3 ), younger age of onset (β: − 480.4, p < 0.0001), lifetime cannabis use (β: 262.6, p = 0.036) and White ethnicity (relative to Asian and Mixed, β: − 5410.3, p = 0.010) were associated with a significant increase in DUP. Additionally, the analysis revealed a significant interaction between age of onset and ethnicity: amongst the White and Black groups earlier onset was strongly associated with longer DUP; whereas for the Asian and Mixed group, earlier onset was only weakly associated with relatively longer DUP.
|Parameter||Variable estimates||DUP estimates mean (95% CI)||Parameters estimates|
|n (valid%)||β||Sig.||95% CI|
|Age of onset||73 (100%)||623.9 (327.6–920.2)||− 480.4||< 0.0001||− 543.6 to − 417.3|
|Lifetime Cannabis Use|
|No#||33 (45.2%)||548.6 (101.8–995.3)||–||–||–|
|Yes||40 (54.8%)||686.0 (273.3–1098.8)||262.6||0.036||17.9 to 507.3|
|Ethnicity (3 broad categories)|
|White#||21 (28.8%)||1268.1 (497.9–2038.3)||–||–||–|
|Black||32 (43.8%)||444.9 (19.9–869.9)||212.7||0.798||− 1863.2 to 1437.8|
|Asian & mixed||20 (27.4%)||233.8 (48.2–419.4)||5410.3||0.010||− 9470.4 to − 1350.2|
|Ethnicity*age of onset|
|Age of onset*White#||–||–||–|
|Age of onset*Black||− 3.1||0.952||− 104.9 to 98.7|
|Age of onset*Asian & mixed||309.3||0.013||68.2 to 550.3|
Note: R Squared: 86.7%, Adjusted R Squared: 85.5%.
DUP: Duration of Untreated Psychosis; #: Reference category; β = Beta; Sig. = statistical significance; 95% CI = 95% Confidence Intervals.
3.4. Differential profiles for adolescent ethnic groups included in the general linear model (n = 73)
- (i) A significant DUP difference amongst ethnic categories was found, with the White group displaying the longer median DUP (White, n = 21, median: 454 days, IQR: 253.5–2176; Black, n = 32, median: 99 days, IQR: 7.25–319.25; Asian and mixed group, n = 20, median: 28.5 days, IQR: 6.25–280), p = 0.001 ( Fig. 3 ). After Bonferroni correction, differences remained significant for the comparison of White versus Black ethnicity (p = 0.003), and White versus Asian and Mixed ethnicity (p = 0.006).
- (ii) The White group was the heaviest cannabis using group (n = 16, 76.2%), followed by the Asian and Mixed group (n = 11, 55.0%) and the Black group (n = 13, 40.6%), p = 0.039.
- (iii) Age of onset percentiles revealed a differentiated pattern: the White group presented a lower average age of onset for the 5 to 15 centiles (8.02–13.89 years) in comparison to those of the Black (10.57–15.54 years) and the Asian and Mixed groups (14.68–16.24 years).
This is the first study examining differences in DUP between adolescent and adult-onset FEP in the UK, and would appear to be the largest study of its kind carried out in the world. The time periods for adolescents to receive treatment and to be referred to the EIS were more than twice that of adults. Significant differences were found amongst adolescent ethnic groups, with the adolescent White group being the only one whose median DUP was far greater than the UK Department of Health target. White ethnicity (relative to Asian and Mixed groups), younger age of onset and lifetime cannabis use contributed to treatment delay in the adolescent group.
The treatment delay rates amongst UK adolescents were in line with those from Australia ( Schimmelmann et al., 2007 ) and lower than those from North America (Ballageer et al, 2005 and White et al, 2006). Clinical, functional and neuropsychological comparisons have not explained DUP differences between age groups. Many plausible reasons for treatment delay may apply to adolescents. First, difficulties in identifying psychosis at early presentations ( Rosen et al., 2006 ) as well as the low stability of psychotic experiences ( Dominguez et al., 2011 ) and diagnoses ( Menezes and Milovan, 2000 ). Second, insidious or atypical clinical presentations may lead adolescents to be referred to teachers or youth welfare services rather than health professionals, with possible delays in identifying psychosis and accessing health care treatment. Third, families as well as professionals may attribute behavioral and emotional problems to adolescent turmoil which may delay referral to mental health services. Fourth, adolescents may be more reluctant to see psychiatrists, delaying detection and treatment ( de Haan et al., 2004 ).
Ethnicity was found to be one of the key factors associated with treatment delay amongst adolescents, showing significant differences between the White and ethnic minority groups. Our findings are consistent with UK studies of adult psychosis that found shorter DUP amongst Black African patients compared with White British patients ( Morgan et al., 2006 ). DUP differences have not been explained by differential clinical presentations amongst ethnic groups but might be partially explained by differential pathways to care ( Ghali et al., 2012 ). A UK sample reported an overrepresentation of Black adolescents with psychosis in in-patients units and a higher probability of involuntary admission and detention ( Tolmac and Hodes, 2004 ); potentially resulting in earlier implementation of antipsychotic medication. Moreover, our study showed that the shortest median DUP was displayed by the adolescent Asian and mixed group. Consistent with this, a Canadian study found that Asian individuals were more likely to use emergency services as their first point of contact ( Archie et al., 2010 ), which might result in earlier treatment.
Cannabis use was found to be a predictor of longer DUP. Although most young people who use cannabis do so without experiencing adverse consequences, a vulnerable minority may experience harmful outcomes, including depression, anxiety and psychotic symptoms (Patton et al, 2002 and Di Forti et al, 2009). There is accumulating evidence of an association between cannabis use and psychosis ( Zammit et al., 2008 ) with early adolescent use of cannabis particularly increasing risk of adult schizophreniform disorder ( Arseneault et al., 2002 ), and earlier presentations (Large et al, 2011 and Stone et al, 2013). Treatment delay in adolescents using cannabis might be tentatively explained by cannabis use masking psychopathology ( Henquet et al., 2010 ), and thus potentially reducing individual, family and professionals' perceptions about need for treatment.
In our study, the White adolescent group was shown to be the heaviest cannabis using group and to report the earliest age of onset, but the three factors (ethnicity, cannabis use and age of onset) independently predicted treatment delay. The substance misuse rate is consistent with the higher rate reported by the White British group in adult psychosis ( Ghali et al., 2012 ). Genetic studies have reported considerable variability in the development of psychosis ( Henquet et al., 2009 ) and its age of presentation ( Estrada et al., 2011 ) when cannabis use and catechol-methyl-transferase (COMT) polymorphisms variations were examined. Variations in the COMT gene have been extensively studied as a putative risk factor for psychosis ( Caspi et al., 2005 ) although the replication of these findings has shown controversial results ( Zammit et al., 2011 ), suggesting that they might apply to a subgroup of the population (Henquet et al, 2006 and Henquet et al, 2009). COMT variations across ethnic groups and cannabis use might partly explain differences in age of onset and treatment delay. Nevertheless, socio-cultural factors may also play a role in the identification of symptoms, attribution of meaning and levels of stigma impacting on help-seeking behavior.
Our findings highlight the need for detection and management of psychosis at early stages, where physicians and mental health professionals may play a crucial role. However, general practitioner education campaigns and dedicated EIS by themselves have not shown to reduce DUP ( Lloyd-Evans et al., 2011 ). More initiatives targeting young people, their families and non-health professionals should be conducted. Problem recognition in psychotic presentations is a complicated process that may well start with the interaction between the young person and their significant others. Family awareness might be a key step in early recognition of psychotic presentations that could otherwise be interpreted as adolescent turmoil. Additionally, health systems need to inspect the impact of referral routes on psychosis treatment; in the UK involvement of child and adolescent mental health teams has shown to be crucial in reducing DUP in adolescents ( Cratsley et al., 2008 ).
Given the multifactorial contribution to treatment delay in adolescent psychosis, future research needs to comprise different approaches, including that of investigating: (i) young people's, families' and cultural attitudes to mental illness, service use and treatment, (ii) professionals' management of adolescents with psychotic presentations, and (iii) differential pathways to care for ethnic groups amongst adolescents. This may help elucidate the determinants leading to treatment delay and develop new strategies for appropriately managing adolescent psychosis.
First, age of onset was only available for 69.8% (n = 940) of the original sample. This could potentially have influenced the results but no sociodemographic differences were found with those excluded. The current study still includes the largest sample size both for the adolescent and adult-onset groups to date. Second, age of onset revealed 15 individuals whose FPS were identified below age 14. This distribution raises the question about whether experiences in this age group were true psychotic experiences. Third, data on age of onset and DUP were unavoidably retrospective. Conceptual and methodological problems hinder the measurement of DUP retrospectively ( Norman and Malla, 2001 ), but these inevitable limitations also existed in comparable studies. Fourth, clinical information on individuals' presentation was only available at EIS entry, so that clinical variables with a high potential for influencing DUP could not be explored further. Fifth, given the relatively small cell sizes for the ethnicity analyses and the heterogeneity of the ethnic categories, caution is required in interpreting the results and further replication of findings would be desirable.
Role of funding bodies
M.D.G. Dominguez: Supported by an Alicia Koplowitz Foundation Fellowship; H.L. Fisher: Funded by a UK Medical Research Council-Population Health Scientist fellowship; B. Major, B. Chisholm, N. Rahaman, J. Joyce, J. Woolley, J. Lawrence, M. Hinton, K. Marlowe, K. Aitchison, S. Johnson and M. Hodes: Nothing to report. K. Aitchison: Currently holding an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta.
H.L. Fisher and S. Johnson conceived and designed the larger MiData project. M.D.G. Dominguez and M. Hodes designed the study hypothesis. M.D.G. Dominguez undertook the statistical analysis. M.D.G. Dominguez and M. Hodes worked on the interpretation of the data. M.D.G. Dominguez wrote the first draft of the manuscript. B. Major, B. Chisholm, N. Rahaman, J. Joyce, J. Woolley, Jo Lawrence, M. Hinton, K. Marlowe, and K. Aitchison revised the articule for important intellectual content. All authors contributed to and have approved the final manuscript.
Conflict of interests
All authors: Nothing to report. K. Aitchison has been on the Advisory Board for the Bristol-Myers Squibb and Otsuka Pharmaceuticals Ltd, and in addition received consultancy fees including payment for lectures and educational presentations from the same company. She was previously a member of various advisory boards, receiving consultancy fees and honoraria, and has received research grants from various companies including Lundbeck and GlaxoSmithKline.
MiData was supported by the London Development Centre for Mental Health, with an initial pilot funded by Islington PCT. These funding bodies had no further role in study design, data management and interpretation, writing up and paper submission. We are extremely grateful to clinicians and patients from the MiData Consortium: C&I-EIS, COAST, EQUIP, STEP, Lewisham-EIS, THEIS, Wandsworth-EIS, KCW-EIS, and Brent-EIS, as well as to Joseph Eliahoo, PhD. for statistical advice.
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a Academic Unit of Child and Adolescent Psychiatry, Division of Brain Sciences, Imperial College London, UK
b Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
c EQUIP, Hackney, East London & City Mental Health Trust, London, UK
d Wandsworth EIS, Southwest London & St. Georges' Mental Heath NHS Trust, London, UK
e Kensington, Chelsea, Westminster EIS, CNWL NHS Foundation Trust, London, UK
f Lewisham EIS, SLaM NHS Foundation Trust, London, UK
g STEP, Southwark, SLaM NHS Foundation Trust, London, UK
h Camden & Islington EIS C&I NHS Foundation Trust, London, UK
i THEIS, Tower Hamlets, East London NHS Foundation Trust, London, UK
j Department of Mental Health Sciences, University College London, UK
k Departments of Psychiatry and Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Corresponding author at: Academic Unit of Child and Adolescent Psychiatry, Imperial College London, St. Mary’s Campus, Norfolk Place, London W2 1PG, UK. Tel.: + 44 20 3312 1145; fax: + 44 20 3312 6299.
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