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James Kirkbride

University College London, Division of Psychiatry, Faculty Member

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I am Professor of Psychiatric and Social Epidemiology at the Division of Psychiatry, UCL, interested in the social determinants of psychosis at multiple levels of causation across the life course. My research focusses on investigating why migrants and their descendants experience elevated rates of psychosis, and why rates of psychosis are elevated in urban environments. My research group, PsyLife (www.psylife.eu), addresses these inequalities by applying several epidemiological techniques (multilevel modelling, Bayesian modelling, multiple imputation, causal inference methods) to various datasets, including large epidemiological studies of first episode psychosis (AESOP, ELFEP, SEPEA, EU-GEI) and longitudinal cohort data (ALSPAC, Swedish register data, Chilean registry data).

Using this knowledge, we have developed a translational epidemiological prediction model to forecast expected need for psychosis in different populations (www.psymaptic.org). This informs Early Intervention in Psychosis service commissioners and planners about expected need for psychosis in the populations they serve. It has informed NICE guidance in England on EIP service provision since 2014, and has also been developed for use in Wales, the Republic of Ireland and Chile.

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Papers by James Kirkbride

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study

Psychological Medicine, 2021

Background A history of childhood adversity is associated with psychotic disorder, with an increa... more Background A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Methods We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effec...

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Molecular Psychiatry, 2021

Important questions remain about the profile of cognitive impairment in psychotic disorders acros... more Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range =-0.45 to-0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES =-0.14 to-0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range =-0.88 to-0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range =-0.13 to-0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range =-0.21 to-0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies

Molecular Psychiatry, 2021

Promotion of good mental health, prevention, and early intervention before/at the onset of mental... more Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset ...

Migration history and risk of psychosis: results from the multinational EU-GEI study

Psychological Medicine, 2021

BackgroundPsychosis rates are higher among some migrant groups. We hypothesized that psychosis in... more BackgroundPsychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration.MethodsWe used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case–control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models.ResultsIn total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06–2.44, p = 0.027) and post-migration social disadvantages (O...

Personality disorder in an Early Intervention Psychosis cohort: Findings from the Social Epidemiology of Psychoses in East Anglia (SEPEA) study v1 (protocols.io.bf3hjqj6)

protocols.io, 2020

The independent and combined influence of schizophrenia polygenic risk score and heavy cannabis use on risk for psychotic disorder: A case-control analysis from the EUGEI study

Background: Some recent studies have challenged the direction of causality for the association be... more Background: Some recent studies have challenged the direction of causality for the association between cannabis use and psychotic disorder, suggesting that cannabis use initiation is explained by common genetic variants associated with risk of schizophrenia. We used data from the European Union Gene-Environment Interaction consortium (EUGEI) case-control study to test for the independent and combined effect of heavy cannabis use, and of Schizophrenia Polygenic risk score (SZ PRS), on risk for psychotic disorder. Methods: Genome-wide data were obtained from 492 first episode psychosis patients (FEPp) and from 787 controls of European Ancestry, and used to generate SZ PRS from the summary results of an independent meta-analysis. Information on pattern of cannabis use was used to build a 7-level frequency-type composite cannabis use measure that we previously found was a strong predictor of psychotic disorder. Results: SZ PRS did not predict cannabis initiation (b=0.027; p=0.51) or how...

Early Parental Death and Risk of Psychosis in Offspring: A Six-Country Case-Control Study

Journal of Clinical Medicine, 2019

Evidence for early parental death as a risk factor for psychosis in offspring is inconclusive. We... more Evidence for early parental death as a risk factor for psychosis in offspring is inconclusive. We analyzed data from a six-country, case-control study to examine the associations of early parental death, type of death (maternal, paternal, both), and child’s age at death with psychosis, both overall and by ethnic group. In fully adjusted multivariable mixed-effects logistic regression models, experiencing early parental death was associated with 1.54-fold greater odds of psychosis (95% confidence interval (CI): 1.23, 1.92). Experiencing maternal death had 2.27-fold greater odds (95% CI: 1.18, 4.37), paternal death had 1.14-fold greater odds (95% CI: 0.79, 1.64), and both deaths had 4.42-fold greater odds (95% CI: 2.57, 7.60) of psychosis compared with no early parental death. Experiencing parental death between 11 and 16 years of age had 2.03-fold greater odds of psychosis than experiencing it before five years of age (95% CI: 1.02, 4.04). In stratified analyses, experiencing the dea...

International incidence of psychotic disorders, 2002–17: a systematic review and meta-analysis

The Lancet Public Health, 2019

Background The last comprehensive systematic review of the incidence of psychotic disorders was p... more Background The last comprehensive systematic review of the incidence of psychotic disorders was published in 2004. New epidemiological data from different settings now permit a broader understanding of global variation. We examined the variation in psychosis by demographic characteristics and study method. Methods For this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, PsycINFO, and bibliographies, and directly contacted first authors. We sought to obtain citations of original research published between Jan 1, 2002, and Dec 31, 2017, on incidence of non-organic adult-onset psychotic disorder. We included papers that were published or in grey literature and had no language restrictions. Data were extracted from published reports, where possible, by sex, age, and ethnic group. Quality of yield was assessed. Data were assessed using univariable randomeffects meta-analysis and meta-regression. We registered our systematic review on PROSPERO, number CRD42018086800. Findings From 56 721 records identified, 177 met inclusion criteria. The pooled incidence of all psychotic disorders was 26•6 per 100 000 person-years (95% CI 22•0-31•7). Heterogeneity was high (I²≥98•5%). Men were at higher risk of all psychotic disorders (incidence rate ratio 1•44 [1•27-1•62]) and non-affective disorders (1•60 [1•44-1•77]) than women, but not affective psychotic disorders (0•87 [0•75-1•00]). Ethnic minorities were also at excess risk of all psychotic disorders (1•75 [1•53-2•00]), including non-affective disorders (1•71 [1•40-2•09]). Meta-regression revealed that population registers reported higher rates of non-affective disorders (9•64 [2•72-31•82]), schizophrenia (2•51 [1•24-5•21]), and bipolar disorder (4•53 [2•41-8•51]) than first contact study designs. Interpretation We found marked variation in incidence of psychotic disorders by personal characteristics and place. Some geographical variation could be partially explained by differences in case ascertainment methods.

The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study

The Lancet Psychiatry, 2019

Background Cannabis use is associated with increased risk of later psychotic disorder but whether... more Background Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder. Methods We included patients aged 18-64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of cannabis use carried the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of Δ⁹-tetrahydrocannabinol (THC) in the different types of cannabis available across the sites, we divided the types of cannabis used by participants into two categories: low potency (THC <10%) and high potency (THC ≥10%). Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites. Findings Between May 1, 2010, and April 1, 2015, we obtained data from 901 patients with first-episode psychosis across 11 sites and 1237 population controls from those same sites. Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3•2, 95% CI 2•2-4•1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4•8, 2•5-6•3). The PAFs calculated indicated that if high-potency cannabis were no longer available, 12•2% (95% CI 3•0-16•1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30•3% (15•2-40•0) in London and 50•3% (27•4-66•0) in Amsterdam. The adjusted incident rates for psychotic disorder were positively correlated with the prevalence in controls across the 11 sites of use of high-potency cannabis (r = 0•7; p=0•0286) and daily use (r = 0•8; p=0•0109). Interpretation Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health.

Understanding Racial-Ethnic Disparities in Psychosis Outcomes via Population-Based Approaches

Psychiatric Services, 2018

Ten-Year Outcomes of First-Episode Psychoses in the MRC ÆSOP-10 Study

The Journal of nervous and mental disease, Jan 20, 2015

It has long been held that schizophrenia and other psychotic disorders have a predominately poor ... more It has long been held that schizophrenia and other psychotic disorders have a predominately poor course and outcome. We have synthesized information on mortality, clinical and social outcomes from the ÆSOP-10 multicenter study, a 10-year follow-up of a large epidemiologically characterized cohort of 557 people with first-episode psychosis. Symptomatic remission and recovery were more common than previously believed. Distinguishing between symptom and social recovery is important given the disparity between these; even when symptomatic recovery occurs social inclusion may remain elusive. Multiple factors were associated with an increased risk of mortality, but unnatural death was reduced by 90% when there was full family involvement at first contact compared with those without family involvement. These results suggest that researchers, clinicians and those affected by psychosis should countenance a much more optimistic view of symptomatic outcome than was assumed when these condition...

Risk of psychotic disorders in migrants to Australia

Psychological Medicine, 2020

BackgroundCertain migrant groups are at an increased risk of psychotic disorders compared to the ... more BackgroundCertain migrant groups are at an increased risk of psychotic disorders compared to the native-born population; however, research to date has mainly been conducted in Europe. Less is known about whether migrants to other countries, with different histories and patterns of migration, such as Australia, are at an increased risk for developing a psychotic disorder. We tested this for first-generation migrants in Melbourne, Victoria.MethodsThis study included all young people aged 15–24 years, residing in a geographically-defined catchment area of north western Melbourne who presented with a first episode of psychosis (FEP) to the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1 January 2011 and 31 December 2016. Data pertaining to the at-risk population were obtained from the Australian 2011 Census and incidence rate ratios were calculated and adjusted for age, sex and social deprivation.ResultsIn total, 1220 young people presented with an FEP during the 6-...

Childhood Maltreatment, Educational Attainment, and IQ: Findings From a Multicentric Case-control Study of First-episode Psychosis (EU-GEI)

Schizophrenia Bulletin, 2022

Background and hypothesis Evidence suggests that childhood maltreatment (ie, childhood abuse and ... more Background and hypothesis Evidence suggests that childhood maltreatment (ie, childhood abuse and childhood neglect) affects educational attainment and cognition. However, the association between childhood maltreatment and Intelligence Quotient (IQ) seems stronger among controls compared to people with psychosis. We hypothesised that: the association between childhood maltreatment and poor cognition would be stronger among community controls than among people with first-episode of psychosis (FEP); compared to abuse, neglect would show stronger associations with educational attainment and cognition; the association between childhood maltreatment and IQ would be partially accounted for by other risk factors; and the association between childhood maltreatment, educational attainment, and IQ would be stronger among patients with affective psychoses compared to those with nonaffective psychoses. Study Design 829 patients with FEP and 1283 community controls from 16 EU-GEI sites were asses...

The psychogenic city

Oxford Medicine Online, 2019

Do cities cause psychosis? Over 50% of the world’s population now live in cities, a figure set to... more Do cities cause psychosis? Over 50% of the world’s population now live in cities, a figure set to rise to two-thirds by 2050. This unprecedented change in the organization of human populations will have both positive and negative consequences on a wide variety of social, political, economic, and health-related domains for individuals and society. In this chapter, we focus on one potentially negative consequence of city living; namely, raised risks of non-affective psychotic disorders in urban populations. We review the possible drivers of this phenomenon, which range from a causal role for exposure to deleterious factors in our urban environments through to non-causal factors, such as reverse causation—or social drift—potentially spanning several generations. We conclude by linking current epidemiological evidence with the latest findings from genetics and social neuroscience on this important public mental health issue.

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Translational Psychiatry, 2021

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using ... more Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and th...

The epidemiological burden of major psychiatric disorders

Incidence: The number (frequency, rate, or proportion) of new healthrelated events in a defined p... more Incidence: The number (frequency, rate, or proportion) of new healthrelated events in a defined population within a specified period of time [1] . Prevalence: The total number of individuals with a healthrelated event at a particular time/ period in a defined population [1] . Point prevalence: The proportion of individuals with the condition at a specified point in time. Period prevalence: The proportion of people with the condition at any point during a specified time period (e.g. annual prevalence or lifetime prevalence). Measures of effect: Measures of effect summarize the strength of the relationship between an exposure and outcome, showing the amount of change a particular exposure has in the frequency or risk of the outcome [2, 3]. Measures of effect are used to compare the frequency of an outcome between two groups in relative or absolute terms [2] . Common relative effect measures include odds ratios and relative risks. Absolute effect measures include risk differences or ‘n...

[RoI Psychosis Incidence review] Datasets, documents

Systematic review materials for the incidence of psychotic disorders in Ireland

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated With Common Genetic Variants for Major Psychiatric Conditions: Results From the Multi-Center EU-GEI Study

Schizophrenia Bulletin, 2021

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagn... more Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic...

Understanding the excess psychosis risk in ethnic minorities: the impact of structure and identity

Social Psychiatry and Psychiatric Epidemiology, 2021

Purpose Psychotic disorders, which are associated with substantially increased morbidity and mort... more Purpose Psychotic disorders, which are associated with substantially increased morbidity and mortality, are up to five times more common in some ethnic minority groups compared with the white majority in Western countries. This long-standing and well-replicated public mental health disparity has hitherto largely eluded adequate explanation. We argue that this might have arisen in part due to the lack of attention given to theoretical work characterising the complex and multidimensional social nature of ethnicity by those epidemiological investigations that have dominated the literature. Methods To bridge this gap, we draw on theoretical and empirical literature from across the social sciences considering the ontological significance of ethnicity (as biology, migration, racialised structures and identity) and its relationships with psychotic disorders to illuminate probable drivers of excess psychosis risk. Results The largest gains in our theoretical understanding of excess psychosi...

Readmission after discharge from acute mental healthcare among 231 988 people in England: cohort study exploring predictors of readmission including availability of acute day units in local areas

BJPsych Open, 2021

Background In the UK, acute mental healthcare is provided by in-patient wards and crisis resoluti... more Background In the UK, acute mental healthcare is provided by in-patient wards and crisis resolution teams. Readmission to acute care following discharge is common. Acute day units (ADUs) are also provided in some areas. Aims To assess predictors of readmission to acute mental healthcare following discharge in England, including availability of ADUs. Method We enrolled a national cohort of adults discharged from acute mental healthcare in the English National Health Service (NHS) between 2013 and 2015, determined the risk of readmission to either in-patient or crisis teams, and used multivariable, multilevel logistic models to evaluate predictors of readmission. Results Of a total of 231 998 eligible individuals discharged from acute mental healthcare, 49 547 (21.4%) were readmitted within 6 months, with a median time to readmission of 34 days (interquartile range 10–88 days). Most variation in readmission (98%) was attributable to individual patient-level rather than provider (trust...

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study

Psychological Medicine, 2021

Background A history of childhood adversity is associated with psychotic disorder, with an increa... more Background A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Methods We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effec...

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Molecular Psychiatry, 2021

Important questions remain about the profile of cognitive impairment in psychotic disorders acros... more Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range =-0.45 to-0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES =-0.14 to-0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range =-0.88 to-0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range =-0.13 to-0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range =-0.21 to-0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies

Molecular Psychiatry, 2021

Promotion of good mental health, prevention, and early intervention before/at the onset of mental... more Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset ...

Migration history and risk of psychosis: results from the multinational EU-GEI study

Psychological Medicine, 2021

BackgroundPsychosis rates are higher among some migrant groups. We hypothesized that psychosis in... more BackgroundPsychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration.MethodsWe used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case–control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models.ResultsIn total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06–2.44, p = 0.027) and post-migration social disadvantages (O...

Personality disorder in an Early Intervention Psychosis cohort: Findings from the Social Epidemiology of Psychoses in East Anglia (SEPEA) study v1 (protocols.io.bf3hjqj6)

protocols.io, 2020

The independent and combined influence of schizophrenia polygenic risk score and heavy cannabis use on risk for psychotic disorder: A case-control analysis from the EUGEI study

Background: Some recent studies have challenged the direction of causality for the association be... more Background: Some recent studies have challenged the direction of causality for the association between cannabis use and psychotic disorder, suggesting that cannabis use initiation is explained by common genetic variants associated with risk of schizophrenia. We used data from the European Union Gene-Environment Interaction consortium (EUGEI) case-control study to test for the independent and combined effect of heavy cannabis use, and of Schizophrenia Polygenic risk score (SZ PRS), on risk for psychotic disorder. Methods: Genome-wide data were obtained from 492 first episode psychosis patients (FEPp) and from 787 controls of European Ancestry, and used to generate SZ PRS from the summary results of an independent meta-analysis. Information on pattern of cannabis use was used to build a 7-level frequency-type composite cannabis use measure that we previously found was a strong predictor of psychotic disorder. Results: SZ PRS did not predict cannabis initiation (b=0.027; p=0.51) or how...

Early Parental Death and Risk of Psychosis in Offspring: A Six-Country Case-Control Study

Journal of Clinical Medicine, 2019

Evidence for early parental death as a risk factor for psychosis in offspring is inconclusive. We... more Evidence for early parental death as a risk factor for psychosis in offspring is inconclusive. We analyzed data from a six-country, case-control study to examine the associations of early parental death, type of death (maternal, paternal, both), and child’s age at death with psychosis, both overall and by ethnic group. In fully adjusted multivariable mixed-effects logistic regression models, experiencing early parental death was associated with 1.54-fold greater odds of psychosis (95% confidence interval (CI): 1.23, 1.92). Experiencing maternal death had 2.27-fold greater odds (95% CI: 1.18, 4.37), paternal death had 1.14-fold greater odds (95% CI: 0.79, 1.64), and both deaths had 4.42-fold greater odds (95% CI: 2.57, 7.60) of psychosis compared with no early parental death. Experiencing parental death between 11 and 16 years of age had 2.03-fold greater odds of psychosis than experiencing it before five years of age (95% CI: 1.02, 4.04). In stratified analyses, experiencing the dea...

International incidence of psychotic disorders, 2002–17: a systematic review and meta-analysis

The Lancet Public Health, 2019

Background The last comprehensive systematic review of the incidence of psychotic disorders was p... more Background The last comprehensive systematic review of the incidence of psychotic disorders was published in 2004. New epidemiological data from different settings now permit a broader understanding of global variation. We examined the variation in psychosis by demographic characteristics and study method. Methods For this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, PsycINFO, and bibliographies, and directly contacted first authors. We sought to obtain citations of original research published between Jan 1, 2002, and Dec 31, 2017, on incidence of non-organic adult-onset psychotic disorder. We included papers that were published or in grey literature and had no language restrictions. Data were extracted from published reports, where possible, by sex, age, and ethnic group. Quality of yield was assessed. Data were assessed using univariable randomeffects meta-analysis and meta-regression. We registered our systematic review on PROSPERO, number CRD42018086800. Findings From 56 721 records identified, 177 met inclusion criteria. The pooled incidence of all psychotic disorders was 26•6 per 100 000 person-years (95% CI 22•0-31•7). Heterogeneity was high (I²≥98•5%). Men were at higher risk of all psychotic disorders (incidence rate ratio 1•44 [1•27-1•62]) and non-affective disorders (1•60 [1•44-1•77]) than women, but not affective psychotic disorders (0•87 [0•75-1•00]). Ethnic minorities were also at excess risk of all psychotic disorders (1•75 [1•53-2•00]), including non-affective disorders (1•71 [1•40-2•09]). Meta-regression revealed that population registers reported higher rates of non-affective disorders (9•64 [2•72-31•82]), schizophrenia (2•51 [1•24-5•21]), and bipolar disorder (4•53 [2•41-8•51]) than first contact study designs. Interpretation We found marked variation in incidence of psychotic disorders by personal characteristics and place. Some geographical variation could be partially explained by differences in case ascertainment methods.

The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study

The Lancet Psychiatry, 2019

Background Cannabis use is associated with increased risk of later psychotic disorder but whether... more Background Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder. Methods We included patients aged 18-64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of cannabis use carried the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of Δ⁹-tetrahydrocannabinol (THC) in the different types of cannabis available across the sites, we divided the types of cannabis used by participants into two categories: low potency (THC <10%) and high potency (THC ≥10%). Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites. Findings Between May 1, 2010, and April 1, 2015, we obtained data from 901 patients with first-episode psychosis across 11 sites and 1237 population controls from those same sites. Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3•2, 95% CI 2•2-4•1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4•8, 2•5-6•3). The PAFs calculated indicated that if high-potency cannabis were no longer available, 12•2% (95% CI 3•0-16•1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30•3% (15•2-40•0) in London and 50•3% (27•4-66•0) in Amsterdam. The adjusted incident rates for psychotic disorder were positively correlated with the prevalence in controls across the 11 sites of use of high-potency cannabis (r = 0•7; p=0•0286) and daily use (r = 0•8; p=0•0109). Interpretation Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health.

Understanding Racial-Ethnic Disparities in Psychosis Outcomes via Population-Based Approaches

Psychiatric Services, 2018

Ten-Year Outcomes of First-Episode Psychoses in the MRC ÆSOP-10 Study

The Journal of nervous and mental disease, Jan 20, 2015

It has long been held that schizophrenia and other psychotic disorders have a predominately poor ... more It has long been held that schizophrenia and other psychotic disorders have a predominately poor course and outcome. We have synthesized information on mortality, clinical and social outcomes from the ÆSOP-10 multicenter study, a 10-year follow-up of a large epidemiologically characterized cohort of 557 people with first-episode psychosis. Symptomatic remission and recovery were more common than previously believed. Distinguishing between symptom and social recovery is important given the disparity between these; even when symptomatic recovery occurs social inclusion may remain elusive. Multiple factors were associated with an increased risk of mortality, but unnatural death was reduced by 90% when there was full family involvement at first contact compared with those without family involvement. These results suggest that researchers, clinicians and those affected by psychosis should countenance a much more optimistic view of symptomatic outcome than was assumed when these condition...

Risk of psychotic disorders in migrants to Australia

Psychological Medicine, 2020

BackgroundCertain migrant groups are at an increased risk of psychotic disorders compared to the ... more BackgroundCertain migrant groups are at an increased risk of psychotic disorders compared to the native-born population; however, research to date has mainly been conducted in Europe. Less is known about whether migrants to other countries, with different histories and patterns of migration, such as Australia, are at an increased risk for developing a psychotic disorder. We tested this for first-generation migrants in Melbourne, Victoria.MethodsThis study included all young people aged 15–24 years, residing in a geographically-defined catchment area of north western Melbourne who presented with a first episode of psychosis (FEP) to the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1 January 2011 and 31 December 2016. Data pertaining to the at-risk population were obtained from the Australian 2011 Census and incidence rate ratios were calculated and adjusted for age, sex and social deprivation.ResultsIn total, 1220 young people presented with an FEP during the 6-...

Childhood Maltreatment, Educational Attainment, and IQ: Findings From a Multicentric Case-control Study of First-episode Psychosis (EU-GEI)

Schizophrenia Bulletin, 2022

Background and hypothesis Evidence suggests that childhood maltreatment (ie, childhood abuse and ... more Background and hypothesis Evidence suggests that childhood maltreatment (ie, childhood abuse and childhood neglect) affects educational attainment and cognition. However, the association between childhood maltreatment and Intelligence Quotient (IQ) seems stronger among controls compared to people with psychosis. We hypothesised that: the association between childhood maltreatment and poor cognition would be stronger among community controls than among people with first-episode of psychosis (FEP); compared to abuse, neglect would show stronger associations with educational attainment and cognition; the association between childhood maltreatment and IQ would be partially accounted for by other risk factors; and the association between childhood maltreatment, educational attainment, and IQ would be stronger among patients with affective psychoses compared to those with nonaffective psychoses. Study Design 829 patients with FEP and 1283 community controls from 16 EU-GEI sites were asses...

The psychogenic city

Oxford Medicine Online, 2019

Do cities cause psychosis? Over 50% of the world’s population now live in cities, a figure set to... more Do cities cause psychosis? Over 50% of the world’s population now live in cities, a figure set to rise to two-thirds by 2050. This unprecedented change in the organization of human populations will have both positive and negative consequences on a wide variety of social, political, economic, and health-related domains for individuals and society. In this chapter, we focus on one potentially negative consequence of city living; namely, raised risks of non-affective psychotic disorders in urban populations. We review the possible drivers of this phenomenon, which range from a causal role for exposure to deleterious factors in our urban environments through to non-causal factors, such as reverse causation—or social drift—potentially spanning several generations. We conclude by linking current epidemiological evidence with the latest findings from genetics and social neuroscience on this important public mental health issue.

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Translational Psychiatry, 2021

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using ... more Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and th...

The epidemiological burden of major psychiatric disorders

Incidence: The number (frequency, rate, or proportion) of new healthrelated events in a defined p... more Incidence: The number (frequency, rate, or proportion) of new healthrelated events in a defined population within a specified period of time [1] . Prevalence: The total number of individuals with a healthrelated event at a particular time/ period in a defined population [1] . Point prevalence: The proportion of individuals with the condition at a specified point in time. Period prevalence: The proportion of people with the condition at any point during a specified time period (e.g. annual prevalence or lifetime prevalence). Measures of effect: Measures of effect summarize the strength of the relationship between an exposure and outcome, showing the amount of change a particular exposure has in the frequency or risk of the outcome [2, 3]. Measures of effect are used to compare the frequency of an outcome between two groups in relative or absolute terms [2] . Common relative effect measures include odds ratios and relative risks. Absolute effect measures include risk differences or ‘n...

[RoI Psychosis Incidence review] Datasets, documents

Systematic review materials for the incidence of psychotic disorders in Ireland

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated With Common Genetic Variants for Major Psychiatric Conditions: Results From the Multi-Center EU-GEI Study

Schizophrenia Bulletin, 2021

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagn... more Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic...

Understanding the excess psychosis risk in ethnic minorities: the impact of structure and identity

Social Psychiatry and Psychiatric Epidemiology, 2021

Purpose Psychotic disorders, which are associated with substantially increased morbidity and mort... more Purpose Psychotic disorders, which are associated with substantially increased morbidity and mortality, are up to five times more common in some ethnic minority groups compared with the white majority in Western countries. This long-standing and well-replicated public mental health disparity has hitherto largely eluded adequate explanation. We argue that this might have arisen in part due to the lack of attention given to theoretical work characterising the complex and multidimensional social nature of ethnicity by those epidemiological investigations that have dominated the literature. Methods To bridge this gap, we draw on theoretical and empirical literature from across the social sciences considering the ontological significance of ethnicity (as biology, migration, racialised structures and identity) and its relationships with psychotic disorders to illuminate probable drivers of excess psychosis risk. Results The largest gains in our theoretical understanding of excess psychosi...

Readmission after discharge from acute mental healthcare among 231 988 people in England: cohort study exploring predictors of readmission including availability of acute day units in local areas

BJPsych Open, 2021

Background In the UK, acute mental healthcare is provided by in-patient wards and crisis resoluti... more Background In the UK, acute mental healthcare is provided by in-patient wards and crisis resolution teams. Readmission to acute care following discharge is common. Acute day units (ADUs) are also provided in some areas. Aims To assess predictors of readmission to acute mental healthcare following discharge in England, including availability of ADUs. Method We enrolled a national cohort of adults discharged from acute mental healthcare in the English National Health Service (NHS) between 2013 and 2015, determined the risk of readmission to either in-patient or crisis teams, and used multivariable, multilevel logistic models to evaluate predictors of readmission. Results Of a total of 231 998 eligible individuals discharged from acute mental healthcare, 49 547 (21.4%) were readmitted within 6 months, with a median time to readmission of 34 days (interquartile range 10–88 days). Most variation in readmission (98%) was attributable to individual patient-level rather than provider (trust...