Development and initial validation of a multivariable predictive Early Adversity Scale for Schizophrenia (EAS-Sz) using register data to quantify environmental risk for adult schizophrenia diagnosis after childhood exposure to adversity.

BACKGROUND: Additional to a child's genetic inheritance, environmental exposures are associated with schizophrenia. Many are broadly described as childhood adversity; modelling the combined impact of these is complex. We aimed to develop and validate a scale on childhood adversity, independent of genetic and other environmental liabilities, for use in schizophrenia risk analysis models, using data from cross-linked electronic health and social services registers. METHOD: A cohort of N = 428 970 Western Australian children born 1980-2001 was partitioned into three samples: scale development sample (N = 171 588), and two scale validation samples (each N = 128 691). Measures of adversity were defined before a child's 10th birthday from five domains: discontinuity in parenting, family functioning, family structure, area-level socioeconomic/demographic environment and family-level sociodemographic status. Using Cox proportional hazards modelling of follow-up time from 10th birthday to schizophrenia diagnosis or censorship, weighted combinations of measures were firstly developed into scales for each domain, then combined into a final global scale. Discrimination and calibration performance were validated using Harrell's C and graphical assessment respectively. RESULTS: A weighted combination of 42 measures of childhood adversity was derived from the development sample. Independent application to identical measures in validation samples produced Harrell's Concordance statistics of 0.656 and 0.624. Average predicted time to diagnosis curves corresponded with 95% CI limits of observed Kaplan-Meier curves in five prognostic categories. CONCLUSIONS: Our Early Adversity Scale for Schizophrenia (EAS-Sz), the first using routinely collected register data, predicts schizophrenia diagnosis above chance, and has potential to help untangle contributions of genetic and environmental liability to schizophrenia risk.

A comparison of trajectories of offending among people with psychotic disorders, other mental disorders and no mental disorders: Evidence from a whole-of-population birth cohort study.

BACKGROUND: Trajectory analysis has been used to study long-term offending patterns and identify offender subgroups, but few such studies have included people with psychotic disorders (PDs) and these have been restricted to adult offenders. AIMS: To compare offending trajectories among 10-26-year-olds with PDs with those with other mental disorders (OMDs) or none (NMD) and identify associated risk factors. METHODS: This is a record-linkage study of 184,147 people born in Western Australia (WA) 1983-1991, drawing on data from WA mental health information system, WA corrective services and other state-wide registers. Group-based trajectory modelling was used to identify offending trajectories. RESULTS: Four offender groups were identified in each mental health status group: G1-no/negligible offending; G2-early onset, adolescent, desisting by age 18; G3-early onset, low rate, offending into early adulthood; and G4-very early onset, high rate, peaking at age 17, continuing into early adulthood. The PDs group had the lowest proportion of individuals with no or negligible offending histories-84% compared with 88.5% in the OMDs group and 96.6% in the no mental disorder group. Within mental health status offender groups, the PDs group was characterised by early or very early onset offending persisting into adulthood, accounting for 5.4% and 3.7% of the group respectively (OMD: 3.8%, 1.5%; NMD: 1.0%, 0.5%). Gender, indigenous status, substance use problems, childhood abuse and parental offending were generally associated with trajectory group membership, although among those with PDs childhood abuse and parental offending were only significant in the early onset-life-course-persistent group. CONCLUSIONS: While most people with PDs never offend, some are disproportionately vulnerable from a particularly early age. If the offending subgroup is to be helped away from criminal justice involvement, interventions must be considered in childhood.

Impact of substance use and other risk factor exposures on conviction rates by people with a psychotic illness and other mental disorders.

PURPOSE: To examine the impact of substance use and other risk factors on conviction rates in people with a psychotic illness (PI) and other mental disorders (OMD) compared to those with no mental illness (NMI). METHODS: This research is part of a longitudinal record-linked whole-population study of 467,945 children born in Western Australia (WA) between 1980 and 2001. This cohort was identified through linkages between the WA psychiatric case register, WA corrective services data and other state-wide registers. We assessed 184,147 individuals born during 1983-1991 to explore the impact of exposure to a variety of risk factors on conviction rates. RESULTS: People with PI and OMD had higher conviction rates than those with NMI, with unadjusted incidence rate ratios (IRR) of 3.98 (95% CI 3.67-4.32) for PI and 3.18 (95% CI 3.03-3.34) for OMD. Adjusting for substance use reduced the rates by 60% in PI and 30% in OMD: IRRs 1.59 (95% CI 1.45-1.74) and 2.24 (2.12-2.37), respectively. Minimal change was seen when adjusting for other potential risk factors (including socio-demographics, victimisation and parental offending), with adjusted IRRs 1.58 (95% CI 1.43-1.74) for PI and 1.90 (95% CI 1.80-2.02) for OMD. CONCLUSIONS: Our analysis shows people with a mental illness have higher rates of conviction than those with NMI. Substance use has a major impact on this rate. Results suggest the need for a greater investment in programs addressing the issue of comorbid substance use with a view to reduce the rate of convictions in this population.

Are familial liability for schizophrenia and obstetric complications independently associated with risk of psychotic illness, after adjusting for other environmental stressors in childhood?

OBJECTIVE: The interplay between genetic and environmental factors on risk for psychotic illness remains poorly understood. The aim of this study was to estimate independent and combined effects of familial liability for schizophrenia and exposure to obstetric complications on risk for developing psychotic illness, covarying with exposure to other environmental stressors. METHODS: This whole-population birth cohort study used record linkage across Western Australian statewide data collections (midwives, psychiatric, hospital admissions, child protection, mortality) to identify liveborn offspring (n = 1046) born 1980-1995 to mothers with schizophrenia, comparing them to offspring of mothers with no recorded psychiatric history (n = 298,370). RESULTS: Both maternal schizophrenia and pregnancy complications were each significantly associated with psychotic illness in offspring, with no interaction. Non-obstetric environmental stressors significantly associated with psychotic illness in offspring included the following: being Indigenous; having a mother who was not in a partnered relationship; episodes of disrupted parenting due to hospitalisation of mother, father or child; abuse in childhood; and living in areas of greatest socioeconomic disadvantage and with elevated rates of violent crime. Adjustment for these other environmental stressors reduced the hazard ratio for maternal schizophrenia substantially (from hazard ratio: 5.7, confidence interval: 4.5-7.2 to hazard ratio: 3.5, confidence interval: 2.8-4.4), but not the estimate for pregnancy complications (hazard ratio: 1.1, confidence interval: 1.0-1.2). The population attributable fraction for maternal schizophrenia was 1.4 and for pregnancy complications was 2.1. CONCLUSION: Our finding of a substantial decrease in risk of psychotic illness associated with familial liability for psychosis following adjustment for other environmental stressors highlights potentially modifiable risk factors on the trajectory to psychotic illness and suggests that interventions that reduce or manage exposure to these risks may be protective, despite a genetic liability.

Congenital blindness is protective for schizophrenia and other psychotic illness. A whole-population study.

Congenital/early blindness is reportedly protective against schizophrenia. Using a whole-population cohort of 467,945 children born in Western Australia between 1980 and 2001, we examined prevalence of schizophrenia and psychotic illness in individuals with congenital/early blindness. Overall, 1870 children developed schizophrenia (0.4%) while 9120 developed a psychotic illness (1.9%). None of the 66 children with cortical blindness developed schizophrenia or psychotic illness. Eight of the 613 children with peripheral blindness developed a psychotic illness other than schizophrenia and fewer had developed schizophrenia. Our results support findings from small case studies that congenital/early cortical but not peripheral blindness is protective against schizophrenia.

Impact of social disadvantage and parental offending on rates of criminal offending among offspring of women with severe mental illness.

OBJECTIVE: Children of parents with severe mental illness have an increased risk of offending. Studies suggest that risk factors such as parental offending and social disadvantage may be associated with the increased risk. This paper assesses the impact of these risk factors on offending rates in the offspring of women with severe mental illness compared to offspring of unaffected women. METHODS: This is part of a longitudinal record-linked whole-population study of 467,945 children born in Western Australia from 1980 to 2001 to mothers with severe mental illness and mothers with no recorded psychiatric illness. These data were linked to Western Australia corrective services data producing a dataset of 12,999 people with at least one offence (3.7% of birth cohort). Cox proportional hazard was used to calculate incidence rate ratios of offspring offending. RESULTS: The offending rate for offspring of mothers with severe mental illness (cases) was almost three times the rate for offspring of unaffected mothers (comparison) with an unadjusted incidence rate ratio of 2.75 (95% confidence interval: [2.58, 2.93]). Adjusting for sex, indigenous status, socio-economic status and geographical remoteness reduced the rate ratio by 24% to incidence rate ratio 2.10, 95% confidence interval: [1.97, 2.23]. Adjusting for parental offending further reduced the rate ratio by 23% to incidence rate ratio 1.62, 95% confidence interval: [1.52, 1.72]. The mean age at first recorded offence was significantly lower for cases compared to comparison offspring. CONCLUSION: Children of mothers with a severe mental illness have a higher rate of offending than children of unaffected mothers, and social disadvantage and parental offending have a major impact on this rate. Services supporting these vulnerable children need to focus on improving the social environment in which they and their families live in.

Sociodemographic, clinical and childhood correlates of adult violent victimisation in a large, national survey sample of people with psychotic disorders.

PURPOSE: Our aim was to establish the 12-month prevalence of violent victimisation in a large sample of adults with psychotic disorders (N = 1825), compare this to population estimates, and examine correlates of violent victimisation. METHODS: The Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18-64 years with psychotic disorders. Interview questions included psychopathology, cognition, sociodemographics, substance use, criminality, and childhood and adult victimisation. Multivariable logistic regression models were used to examine the independent contributions of known risk factors, clinical profile and childhood abuse, on risk of violent victimisation. Differences between men and women were examined. RESULTS: Among adults with psychotic disorders, 12-month prevalence of any victimisation was 38.6% (males 37.4%, females 40.5%), and of violent victimisation was 16.4% (males 15.2%; females 18.3%). Violent victimisation was 4.8 times higher than the population rate of 3.4% (6.5 times higher for women; 3.7 times higher for men). Significant correlates of violent victimisation were established sociodemographic and behavioural risk factors predicting victimisation in the general community: younger age, residence in the most disadvantaged neighbourhoods, homelessness, lifetime alcohol abuse/dependence, and prior criminal offending. Among clinical variables, only mania and self-harm remained significant in the multivariable model. Childhood abuse was independently associated with violent victimisation. CONCLUSIONS: Rates of violent victimisation are high for people with psychotic disorders, especially women, compared to population rates. Greater exposure to sociodemographic and behavioural risks may render them particularly vulnerable to victimisation. Social cognition as a valuable treatment target is discussed.

Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression.

BACKGROUND: Recent evidence points to partially shared genetics of neuropsychiatric disorders. AIMS: We examined risk of intellectual disability and other neuropsychiatric outcomes in 3174 children of mothers with schizophrenia, bipolar disorder or unipolar major depression compared with 3129 children of unaffected mothers. METHOD: We used record linkage across Western Australian population-based registers. The contribution of obstetric factors to risk of intellectual disability was assessed. RESULTS: Children were at significantly increased risk of intellectual disability with odds ratios (ORs) of 3.2 (95% CI 1.8-5.7), 3.1 (95% CI 1.9-4.9) and 2.9 (95% CI 1.8-4.7) in the maternal schizophrenia, bipolar disorder and unipolar depression groups respectively. Multivariate analysis suggests familial and obstetric factors may contribute independently to the risk. Although summated labour/delivery complications (OR = 1.4, 95% CI 1.0-2.0) just failed to reach significance, neonatal encephalopathy (OR = 7.7, 95% CI 3.0-20.2) and fetal distress (OR = 1.8, 95% CI 1.1-2.7) were independent significant predictors. Rates of rare syndromes in children of mothers with mental disorder were well above population rates. Risk of pervasive developmental disorders, including autism, was significantly elevated for children of mothers with bipolar disorder. Risk of epilepsy was doubled for children of mothers with unipolar depression. CONCLUSIONS: Our findings provide epidemiological support for clustering of neuropsychiatric disorders. Further larger epidemiological studies are warranted.