Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.

Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia's alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.

Fine-mapping genomic loci refines bipolar disorder risk genes.

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).

Levels of Involvement with Child Protection Services Associated with Early Adolescent Police Contact as a Victim and Person of Interest.

The relationship between childhood maltreatment and subsequent offending/victimization is well established. However, the magnitude of this relationship for different levels of child protection services (CPS) involvement is poorly understood, due to measurement issues, lack of longitudinal data, and reliance on reports of substantiated maltreatment, which can underestimate the impact of maltreatment. This study examined associations between CPS involvement during childhood (ages 0 to <11 years) and police services contact (as a victim and/or a person of interest) for criminal incidents in early adolescence (11 to ~14 years), differentiated according to levels of CPS involvement (i.e., no risk of significant harm [non-ROSH], unsubstantiated ROSH, substantiated ROSH, and out-of-home care; each examined relative to no CPS contact). Data for 71,465 children were drawn from the New South Wales Child Development Study, an intergenerational, longitudinal investigation that uses administrative records from CPS and police alongside other health, justice, and education data. Multinomial regression analyses were conducted to determine associations between increasing levels of CPS involvement and police contact as a victim only, a person of interest only, and as both victim and person of interest while accounting for covariates (i.e., child's sex, Aboriginal, and/or Torres Strait Islander background, socioeconomic status, maternal age at child's birth, and parental offending history). Children exposed to any of the four levels of CPS involvement had higher odds of police contact, relative to children with no CPS involvement. Odds ratios were higher for contact with police as both a victim and a person of interest, compared to police contact as a victim or a person of interest only. These findings highlight that children with even unsubstantiated CPS reports (i.e., non-ROSH and unsubstantiated ROSH reports) are at heightened risk of police contact compared to children who are unknown to CPS, underlining the need to support all families in contact with CPS.

Alteration of DNA Methylation and Epigenetic Scores Associated With Features of Schizophrenia and Common Variant Genetic Risk.

BACKGROUND: Unpacking molecular perturbations associated with features of schizophrenia is a critical step toward understanding phenotypic heterogeneity in this disorder. Recent epigenome-wide association studies have uncovered pervasive dysregulation of DNA methylation in schizophrenia; however, clinical features of the disorder that account for a large proportion of phenotypic variability are relatively underexplored. METHODS: We comprehensively analyzed patterns of DNA methylation in a cohort of 381 individuals with schizophrenia from the deeply phenotyped Australian Schizophrenia Research Bank. Epigenetic changes were investigated in association with cognitive status, age of onset, treatment resistance, Global Assessment of Functioning scores, and common variant polygenic risk scores for schizophrenia. We subsequently explored alterations within genes previously associated with psychiatric illness, phenome-wide epigenetic covariance, and epigenetic scores. RESULTS: Epigenome-wide association studies of the 5 primary traits identified 662 suggestively significant (p < 6.72 × 10-5) differentially methylated probes, with a further 432 revealed after controlling for schizophrenia polygenic risk on the remaining 4 traits. Interestingly, we uncovered many probes within genes associated with a variety of psychiatric conditions as well as significant epigenetic covariance with phenotypes and exposures including acute myocardial infarction, C-reactive protein, and lung cancer. Epigenetic scores for treatment-resistant schizophrenia strikingly exhibited association with clozapine administration, while epigenetic proxies of plasma protein expression, such as CCL17, MMP10, and PRG2, were associated with several features of schizophrenia. CONCLUSIONS: Our findings collectively provide novel evidence suggesting that several features of schizophrenia are associated with alteration of DNA methylation, which may contribute to interindividual phenotypic variation in affected individuals.

Childhood Schizotypy and Adolescent Mental Disorder.

BACKGROUND AND HYPOTHESIS: Schizotypy provides a framework for understanding the developmental nature of psychotic disorders and a means of identifying "at-risk" individuals early in the lifespan. However, there is a lack of prospective longitudinal research examining the relationship between schizotypy in childhood and later psychotic and other mental disorders. We hypothesized that distinct profiles of schizotypy in childhood would be differentially associated with psychotic and other mental disorders emerging later in adolescence. STUDY DESIGN: In a large population cohort of Australian young people (n = 26 837), we prospectively examined the relationship between person-centered profiles of schizotypy identified in middle childhood (age ~11 years) and adolescent diagnoses (age ~13-18 years) across 7 types of mental disorders using multinomial logistic regression. RESULTS: Membership in any of 3 childhood schizotypy profiles (true schizotypy, affective schizotypy, or introverted schizotypy) was associated with an increased likelihood of being diagnosed with any type of mental disorder in adolescence; effects were strongest for the true schizotypy group (aOR = 3.07, 95% CI = 2.64, 3.57), followed by the introverted (aOR = 1.94, 95% CI = 1.75, 2.15) and affective (aOR = 1.29, 95% CI = 1.13, 1.47) schizotypy groups. Six of the 7 types of mental disorders measured (including psychotic disorders) were associated with at least 1 schizotypy group. CONCLUSIONS: Schizotypy in middle childhood is an important correlate of mental disorders in adolescence; however, it does not appear to be specifically associated with psychotic disorders in this age group.

Early life exposure to air pollution and psychotic-like experiences, emotional symptoms, and conduct problems in middle childhood.

BACKGROUND: Air pollution has been linked to a variety of childhood mental health problems, but results are inconsistent across studies and the effect of exposure timing is unclear. We examined the associations between air pollution exposure at two time-points in early development and psychotic-like experiences (PLEs), and emotional and conduct symptoms, assessed in middle childhood (mean age 11.5 years). METHODS: Participants were 19,932 children selected from the NSW Child Development Study (NSW-CDS) with available linked multi-agency data from birth, and self-reported psychotic-like experiences (PLEs) and psychopathology at age 11-12 years (middle childhood). We used binomial logistic regression to examine associations between exposure to nitrogen dioxide (NO2) and particulate matter less than 2.5 µm (PM2.5) at two time-points (birth and middle childhood) and middle childhood PLEs, and emotional and conduct symptoms, with consideration of socioeconomic status and other potential confounding factors in adjusted models. RESULTS: In fully adjusted models, NO2 exposure in middle childhood was associated with concurrent PLEs (OR = 1.10, 95% CI = 1.02-1.20). Similar associations with PLEs were found for middle childhood exposure to PM2.5 (OR = 1.05, 95% CI = 1.01-1.09). Neither NO2 nor PM2.5 exposure was associated with emotional symptoms or conduct problems in this study. CONCLUSIONS: This study highlights the need for a better understanding of potential mechanisms of action of NO2 in the brain during childhood.

Estimating multimodal brain variability in schizophrenia spectrum disorders: A worldwide ENIGMA study.

Objective: Schizophrenia is a multifaceted disorder associated with structural brain heterogeneity. Despite its relevance for identifying illness subtypes and informative biomarkers, structural brain heterogeneity in schizophrenia remains incompletely understood. Therefore, the objective of this study was to provide a comprehensive insight into the structural brain heterogeneity associated with schizophrenia. Methods: This meta- and mega-analysis investigated the variability of multimodal structural brain measures of white and gray matter in individuals with schizophrenia versus healthy controls. Using the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6139 individuals for a given brain measure, we examined variability in cortical thickness, surface area, folding index, subcortical volume and fractional anisotropy. Results: We found that individuals with schizophrenia are distinguished by higher heterogeneity in the frontotemporal network with regard to multimodal structural measures. Moreover, individuals with schizophrenia showed higher homogeneity of the folding index, especially in the left parahippocampal region. Conclusions: Higher multimodal heterogeneity in frontotemporal regions potentially implies different subtypes of schizophrenia that converge on impaired frontotemporal interaction as a core feature of the disorder. Conversely, more homogeneous folding patterns in the left parahippocampal region might signify a consistent characteristic of schizophrenia shared across subtypes. These findings underscore the importance of structural brain variability in advancing our neurobiological understanding of schizophrenia, and aid in identifying illness subtypes as well as informative biomarkers.

Cumulative comorbidity between neurodevelopmental, internalising, and externalising disorders in childhood: a network approach.

Cumulative comorbidity of mental disorders is common, but the extent and patterns of comorbid psychopathology in childhood are not well established. The current study aimed to elucidate the emergent patterns of cumulative mental disorder comorbidity in children using network analysis of diagnoses recorded between birth and age 12 years. Participants were 90,269 children (mean age 12.7 years; 51.8% male) within the New South Wales Child Development Study (NSW-CDS)-a longitudinal record-linkage cohort study of Australian children born in NSW between 2002 and 2005. Binary indicators for eight types of mental disorder were derived from administrative health records. Patterns of conditional association between mental disorders were assessed utilising network analysis. Of 90,269 children, 2268 (2.5%) had at least one mental disorder by age 12 years; of the 2268 children who had at least one mental disorder by age 12 years, 461 (20.3%) were diagnosed with two or more different disorders out of the eight disorder types included in analyses. All disorders were either directly or indirectly interconnected, with childhood affective and emotional disorders and developmental disorders being most central to the network overall. Mental disorder nodes aggregated weakly (modularity = 0.185) into two communities, representative of internalising and externalising disorders, and neurodevelopmental and sleep disorders. Considerable sex differences in the structure of the mental disorder comorbidity networks were also observed. Developmental and childhood affective and emotional disorders appear to be key to mental disorder comorbidity in childhood, potentially reflecting that these disorders share symptoms in common with many other disorders.

Self-reported traumatic brain injury in a sample of impulsive violent offenders: neuropsychiatric correlates and possible "dose effects".

Background: Traumatic brain injury (TBI) is a major public health problem that may be associated with numerous behavioral problems, including impulsivity, aggression and violence. Rates of self-reported TBI are high within offender populations, but the extent to which TBI is causally implicated in causing illegal behavior is unclear. This study examined the psychological and functional correlates of histories of traumatic brain injury in a sample of impulsive violent offenders. Methods: Study participants, all men, had been recruited to participate in a randomized controlled trial of sertraline to reduce recidivism. Study entry criteria were an age of at least 18 years, a documented history of two or more violent offenses and a score of 70 or above on the Barratt Impulsiveness Scale. An extensive list of standardized questionnaires was administered to obtain information on previous TBI and other neuropsychiatric conditions or symptoms. Results: In the sample of 693 men, 66% were aged between 18 and 35 years old, and 55% gave a history of TBI ("TBI+"). Overall, 55% of study participants reported at least one TBI. High levels of neuropsychiatric symptomatology were reported. In 75% of TBI+ individuals, their most severe TBI (by self-report) was associated with loss of consciousness (LOC) < 30 min. Compared to TBI- (those without history of TBI) participants, TBI+ individuals were more impulsive (Eysenck Impulsivity), irritable, angry, and reported higher levels of assaultive behavior, depressive symptomology, alcohol use disorder, suicidal ideation, suicide attempts, and lower quality of life. Potential "dose effects" of TBI severity and frequency in terms of neuropsychiatric symptomatology were identified. Conclusion: Like other studies of offender populations, single and multiple TBIs were very common. The associations of TBI, TBI severity, and TBI frequency (i.e., TBI "burden") with adverse neuropsychiatric phenomena suggest TBI contributes importantly to offender morbidity but the select nature of the sample and cross-sectional study design constrain the interpretation of these findings.

The full spectrum of clinical stages of psychosis among mentally ill prisoners in New South Wales (NSW), Australia.

Research on the association between psychosis and criminal offending has typically focused on violent offenders with chronic psychotic illness. This stages of psychosis in prison (SOPP) study used a clinical staging approach to identify adult men referred to prison mental health services who had an at-risk mental state (ARMS), first episode of psychosis (FEP) or an established psychotic illness. Of the 105 participants included, 6% were determined to have FEP, 6% met ARMS criteria and the remainder had an established psychotic illness. Compared to a prison control sample, individuals on the psychosis spectrum were found to have higher levels of social disadvantage and other co-occurring mental health and substance use problems but were not more likely to have committed a violent offence. These findings support the notion that risk of criminal justice contact and complex illness burden exist across the full spectrum of psychotic illness.

Self-harm and suicidal ideation among young people is more often recorded by child protection than health services in an Australian population cohort.

OBJECTIVE: We investigated patterns of service contact for self-harm and suicidal ideation recorded by a range of human service agencies - including health, police and child protection - with specific focus on overlap and sequences of contacts, age of first contact and demographic and intergenerational characteristics associated with different service responses to self-harm. METHODS: Participants were 91,597 adolescents for whom multi-agency linked data were available in a longitudinal study of a population cohort in New South Wales, Australia. Self-harm and suicide-related incidents from birth to 18 years of age were derived from emergency department, inpatient hospital admission, mental health ambulatory, child protection and police administrative records. Descriptive statistics and binomial logistic regression were used to examine patterns of service contacts. RESULTS: Child protection services recorded the largest proportion of youth with reported self-harm and suicidal ideation, in which the age of first contact for self-harm was younger relative to other incidents of self-harm recorded by other agencies. Nearly 40% of youth with a health service contact for self-harm also had contact with child protection and/or police services for self-harm. Girls were more likely to access health services for self-harm than boys, but not child protection or police services. CONCLUSION: Suicide prevention is not solely the responsibility of health services; police and child protection services also respond to a significant proportion of self-harm and suicide-related incidents. High rates of overlap among different services responding to self-harm suggest the need for cross-agency strategies to prevent suicide in young people.

Conditions of Birth and Early Childhood Developmental Risk for Mental Disorders.

Distinct classes of children in the general population are at increased odds of later mental illness and other adverse outcomes according to patterns of early childhood developmental vulnerability. If certain risk factors known at the time of birth are reliably associated with membership in early childhood risk classes, then preventative interventions could be initiated in the earliest years of life. Associations between 14 factors known at the time of birth and membership in early childhood risk classes were examined in 66,464 children. Risk class membership was associated with maternal mental illness, parental criminal charges and being male; distinct patterns of association were shown for some conditions, for example, prenatal child protection notification was uniquely associated with misconduct risk'. These findings suggest that risk factors known at the time of birth could assist in very early detection of children who may benefit from early intervention in the first 2000 days.

Item response theory analysis of self-reported social-emotional learning competencies in an Australian population cohort aged 11 years.

Childhood social and emotional competencies are recognized as teachable skills affecting well-being and developmental outcomes across the life span. This study sought to develop and validate a brief self-report measure of social-emotional competencies in middle childhood. The study used items from the 2015 Middle Childhood Survey, administered to a representative subsample of the New South Wales Child Development Study cohort, comprising sixth grade students (n = 26,837; aged 11-12 years) attending primary school in New South Wales, Australia. Exploratory and confirmatory factor analyses assessed the latent structure of social-emotional competencies, and item response theory and construct validity analyses evaluated the reliability, validity, and psychometric properties of the derived measure. A correlated five-factor model outperformed other latent structures (one-factor, higher order, and bifactor models) and was consistent with the framework developed by the Collaborative for Academic, Social, and Emotional Learning that informs the Australian school-based social-emotional learning curriculum, incorporating the following: Self-Awareness; Self-Management; Social Awareness; Relationship Skills; and Responsible Decision-Making. This brief (20-item), psychometrically sound, self-report measure of social-emotional competencies in middle childhood provides capacity for exploration of these skills as mediators and moderators of developmental outcomes across the life span. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Out-of-home care characteristics associated with childhood educational underachievement, mental disorder, and police contacts in an Australian population sample.

BACKGROUND: Children in out-of-home care (OOHC) are generally at increased risk of health and social adversities compared to their peers. However, the experiences of children in OOHC are not uniform and their associated health and social indices may vary in relation to characteristics of OOHC placements and child protection contact. OBJECTIVE: To examine associations between a range of characteristics of OOHC placements and child protection contact (e.g., number, type, and age of placement) with educational underachievement, mental disorder, and police contact (as a victim, witness, or person of interest) in childhood. PARTICIPANTS AND SETTING: Participants were Australian children drawn from the New South Wales Child Development Study cohort who had been placed in OOHC at least once between the ages of 0-13 years (n = 2082). METHODS: Logistic regression was used to examine prospective associations of OOHC placement and child protection contact characteristics (type of carer, placement instability, duration and frequency of maltreatment, and amount of time in care) with educational underachievement, mental disorder diagnosis and any type of police contact. RESULTS: Placements with foster carers, greater placement instability, longer and more frequent exposure to maltreatment, and longer time spent in care were each associated with greater likelihood of consequences in all domains of functioning. CONCLUSIONS: Children with certain placement characteristics are at higher risk of adverse consequences and should be prioritised for support services. The magnitude of relationships was not uniform across different health and social indices, highlighting the need for holistic, multiagency approaches to support children placed in care.

Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations.

Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study-and most other large-scale human genetics studies-was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10-6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

Parental mental disorders and offspring schizotypy in middle childhood: an intergenerational record linkage study.

PURPOSE: To investigate relationships between distinct schizotypy risk profiles in childhood and the full spectrum of parental mental disorders. METHODS: Participants were 22,137 children drawn from the New South Wales Child Development Study, for whom profiles of risk for schizophrenia-spectrum disorders in middle childhood (age ~ 11 years) were derived in a previous study. A series of multinomial logistic regression analyses examined the likelihood of child membership in one of three schizotypy profiles (true schizotypy, introverted schizotypy, and affective schizotypy) relative to the children showing no risk, according to maternal and paternal diagnoses of seven types of mental disorders. RESULTS: All types of parental mental disorders were associated with membership in all childhood schizotypy profiles. Children in the true schizotypy group were more than twice as likely as children in the no risk group to have a parent with any type of mental disorder (unadjusted odds ratio [OR] = 2.27, 95% confidence intervals [CI] = 2.01-2.56); those in the affective (OR = 1.54, 95% CI = 1.42-1.67) and introverted schizotypy profiles (OR = 1.39, 95% CI = 1.29-1.51) were also more likely to have been exposed to any parental mental disorder, relative to children showing no risk. CONCLUSION: Childhood schizotypy risk profiles appear not to be related specifically to familial liability for schizophrenia-spectrum disorders; this is consistent with a model where liability for psychopathology is largely general rather than specific to particular diagnostic categories.

Relationships between parental mental illness and/or offending and offspring contact with the police in childhood: Findings from a longitudinal record-linkage study.

BACKGROUND: Parental offending and mental illness are associated with an increased risk of criminal behaviour in offspring during adolescence and adulthood, but the impact of such problems on younger children, including children's experiences of victimisation, is less well known. AIM: To investigate the associations between parental offending and mental illness recorded prior to their offspring's age of 5 years and their offspring's contact with police as a 'person of interest', 'victim' or 'witness' between ages 5 and 13 years. METHODS: Our sample consisted of 72,771 children and their parents drawn from the New South Wales Child Development Study, an Australian longitudinal population-based record linkage study. Logistic regression analyses were conducted to examine associations between parental factors and offspring's police contact. Separate models examined the relationships between maternal or paternal offending and mental illness, as well as the combination among either or both parents, as the independent variables, and their child's police contact as the dependent variable. RESULTS: Parental offending and mental illness were each individually associated with indices of police contact among offspring. Stronger associations were observed when both offending and mental illness were present together (in either parent, or when one parent had both exposures). Stronger associations were evident for mothers with both factors across all offspring police contact types, relative to fathers with both factors, in fully adjusted models; that is, children of mothers with both factors were over four times as likely to have contact with police as a 'person of interest' (OR = 4.29; 95% CI = 3.75-4.92) and over three times as likely to have contact as a victim (OR = 3.35; 95% CI = 3.01-3.74) or witness (OR = 3.58; 95% CI = 3.03-4.24), than children whose mothers had no history of offending or mental illness. CONCLUSIONS: Children with a parental history of offending and mental illness in early life are at an increased likelihood of early police contact as young as 5-13 years of age; it is vital that this is taken as a signal to help them and their affected families according to need.

Cumulative Environmental Risk in Early Life: Associations With Schizotypy in Childhood.

BACKGROUND AND HYPOTHESIS: Psychotic disorders are associated with a growing number of recognized environmental exposures. Cumulative exposure to multiple environmental risk factors in childhood may contribute to the development of different patterns of schizotypy evident in early life. Hypotheses were that distinct profiles of schizotypy would have differential associations with a cumulative score of environmental risk factors. STUDY DESIGN: We prospectively examined the relationship between 19 environmental exposures (which had demonstrated replicated associations with psychosis) measured from the prenatal period through to age 11 years, and 3 profiles of schizotypy in children (mean age = 11.9 years, n = 20 599) that have been established in population data from the New South Wales-Child Development Study. Multinomial logistic regression was used to examine associations between membership in each of 3 schizotypy profiles (true schizotypy, introverted schizotypy, and affective schizotypy) and exposure to a range of 19 environmental risk factors for psychosis (both individually and summed as a cumulative environmental risk score [ERS]), relative to children showing no risk. RESULTS: Almost all environmental factors were associated with at least 1 schizotypy profile. The cumulative ERS was most strongly associated with the true schizotypy profile (OR = 1.61, 95% CI = 1.52-1.70), followed by the affective (OR = 1.33, 95% CI = 1.28-1.38), and introverted (OR = 1.32, 95% CI = 1.28-1.37) schizotypy profiles. CONCLUSIONS: Consistent with the cumulative risk hypothesis, results indicate that an increased number of risk exposures is associated with an increased likelihood of membership in the 3 schizotypy profiles identified in middle childhood, relative to children with no schizotypy profile.