Childhood trauma moderates schizotypy-related brain morphology: analyses of 1182 healthy individuals from the ENIGMA schizotypy working group.

BACKGROUND: Schizotypy represents an index of psychosis-proneness in the general population, often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy. METHODS: We addressed this question using data from a total of 1182 healthy adults (age range: 18-65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical gray matter volume and cortical thickness were determined. RESULTS: A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of morphological changes directly associated with increasing levels of schizotypy or increasing levels of childhood trauma exposure. CONCLUSIONS: These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.

Patterns of health service use for children with mental disorders in an Australian state population cohort.

OBJECTIVES: The rate of mental health services provided to children and young people is increasing worldwide, including in Australia. The aim of this study was to describe patterns of hospital and ambulatory mental health service use among a large population cohort of adolescents followed from birth, with consideration of variation by age, sex and diagnosis. METHODS: Characteristics of services provided for children with mental disorder diagnoses between birth and age 17.5 years were ascertained for a population cohort of 85,642 children (52.0% male) born between 2002 and 2005, from 'Admitted Patients', 'Emergency Department' and 'Mental Health Ambulatory' records provided by the New South Wales and Australian Capital Territory Health Departments. RESULTS: A total of 11,205 (~13.1%) children received at least one hospital or ambulatory health occasion of service for a mental health condition in the observation period. More than two-fifths of children with mental disorders had diagnoses spanning multiple categories of disorder over time. Ambulatory services were the most heavily used and the most common point of first contact. The rate of mental health service contact increased with age across all services, and for most categories of mental disorder. Girls were more likely to receive services for mental disorders than boys, but boys generally had an earlier age of first service contact. Finally, 3.1% of children presenting to mental health services experienced involuntary psychiatric inpatient admission. CONCLUSIONS: The extent of hospital and ambulatory-based mental healthcare service among children emphasises the need for primary prevention and early intervention.

Cumulative environmental risk in early life is associated with mental disorders in childhood.

BACKGROUND: No single environmental factor is a necessary or sufficient cause of mental disorder; multifactorial and transdiagnostic approaches are needed to understand the impact of the environment on the development of mental disorders across the life course. METHOD: Using linked multi-agency administrative data for 71 932 children from the New South Wales Child Developmental Study, using logistic regression, we examined associations between 16 environmental risk factors in early life (prenatal period to <6 years of age) and later diagnoses of mental disorder recorded in health service data (from age 6 to 13 years), both individually and summed as an environmental risk score (ERS). RESULTS: The ERS was associated with all types of mental disorder diagnoses in a dose-response fashion, such that 2.8% of children with no exposure to any of the environmental factors (ERS = 0), compared to 18.3% of children with an ERS of 8 or more indicating exposure to 8 or more environmental factors (ERS ⩾ 8), had been diagnosed with any type of mental disorder up to age 13-14 years. Thirteen of the 16 environmental factors measured (including prenatal factors, neighbourhood characteristics and more proximal experiences of trauma or neglect) were positively associated with at least one category of mental disorder. CONCLUSION: Exposure to cumulative environmental risk factors in early life is associated with an increased likelihood of presenting to health services in childhood for any kind of mental disorder. In many instances, these factors are preventable or capable of mitigation by appropriate public policy settings.

Early childhood developmental vulnerability associated with parental mental disorder comorbidity.

OBJECTIVES: Parental mental health has a profound influence on the mental health and well-being of their offspring. With comorbid mental disorders generally the rule rather than the exception, increased knowledge of the impact of parental mental disorder comorbidity on early child development may facilitate improved targeting and delivery of early intervention for vulnerable offspring. METHODS: Participants were 66,154 children and their parents in the New South Wales Child Development Study - a prospective, longitudinal, record-linkage study of a population cohort of children born in NSW between 2002 and 2004. Early childhood developmental vulnerability was assessed at age ~5 years using the Australian Early Development Census, and information on parental mental disorders was obtained from administrative health records. Binomial and multinomial logistic regression were used to assess the relationship between parental mental disorders and early childhood developmental vulnerability on emotional and behavioural domains, as well as membership of latent developmental risk classes reflecting particular classes of vulnerability. RESULTS: Multiple diagnoses of mental disorders in mothers and fathers were associated with an increased likelihood of early childhood emotional and behavioural developmental vulnerability in offspring, relative to parents without mental disorder. The likelihood of offspring vulnerability increased with the number of parental comorbidities, particularly maternal comorbidities. CONCLUSION: Early childhood developmental vulnerability was strongly associated with parental mental ill-health, with the strength of associations increasing in line with a greater number of mental disorder diagnoses among mothers and fathers. New and expectant parents diagnosed with multiple mental disorders should be prioritised for intervention, including attention to the developmental well-being of their offspring.

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.

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.

Pathways from developmental vulnerabilities in early childhood to schizotypy in middle childhood.

OBJECTIVES: Childhood disturbances in social, emotional, language, motor and cognitive functioning, and schizotypy have each been implicated as precursors of schizophrenia-spectrum disorders. We investigated whether relationships between early childhood developmental vulnerabilities and childhood schizotypy are mediated by educational underachievement in middle childhood. METHODS: Participants were members of a large Australian (n = 19,216) population cohort followed longitudinally. Path analyses were used to model relationships between developmental vulnerabilities at age ~5 years, educational underachievement from ages ~8 to 10 years and three distinct profiles of schizotypy at age ~11 years (true, introverted and affective schizotypy). RESULTS: Early childhood developmental vulnerabilities on five broad domains (related to physical, emotional, social, cognitive and communication development) were associated with schizotypy profiles in middle childhood. Educational underachievement in middle childhood was associated with all schizotypy profiles, but most strongly with the true schizotypy profile (OR = 3.92, 95% CI = 3.12, 4.91). The relationships between schizotypy profiles and early childhood developmental vulnerabilities in 'language and cognitive skills (school-based)' and 'communication skills and general knowledge' domains were fully mediated by educational underachievement in middle childhood, and the relationships with early childhood 'physical health and well-being' and 'emotional maturity' domains were partially mediated. CONCLUSION: Developmental continuity from early childhood developmental vulnerabilities to schizotypy in middle childhood is mediated by educational underachievement in middle childhood. While some domains of early developmental functioning showed differential relationships with distinct schizotypy profiles, these findings support a developmental pathway to schizotypy in which cognitive vulnerability operates from early childhood through to middle childhood.

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.

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.

Forecasting childhood adversities from conditions of birth.

BACKGROUND: Childbirth presents an optimal time for identifying high-risk families to commence intervention that could avert various childhood health and social adversities. OBJECTIVE: We sought to establish the minimum set of exposures required to accurately predict a range of adverse childhood outcomes up to the age of 13 years, from a set of 14 individual and familial risk exposures evident at the time of birth. METHODS: Participants were 72,059 Australian children and their parents drawn from a multi-register population cohort study (data spanning 1994-2018). Risk exposures included male sex, young mother (aged ≤21 years), no (or late first; >16 weeks) antenatal visit, maternal smoking during pregnancy, small for gestational age, preterm birth, pregnancy complications (any of hypertension, diabetes mellitus, gestational diabetes or pre-eclampsia), >2 previous pregnancies of ≥20 weeks, socio-economic disadvantage, prenatal child protection notification, and maternal or paternal mental disorder or criminal offending history. Individual outcomes included early childhood developmental vulnerability (age 5 years), sustained educational underachievement (age 8 and 10 years), mental disorder diagnoses, substantiated childhood maltreatment, and contact with the police as a victim or person-of-interest up to age 13-14 years. RESULTS: Risk exposures at birth predicted individual childhood outcomes with fair to excellent accuracy: the area under the receiver operating characteristic curves ranged between 0.60 (95% CI 0.58, 0.62) for childhood mental disorder and 0.83 (95% CI 0.82, 0.85) for substantiated child maltreatment. The presence of five or more exposures characterised 12-25% of children with one or more adverse outcomes and showed high predictive certainty for models predicting multiple outcomes, which were apparent in 9% of the population. CONCLUSIONS: Up to a quarter of the neonatal population at risk of multiple adverse outcomes can be detected at birth, with implications for population health screening. However, cautious implementation of these models is warranted, given their relatively low positive predictive values.

Interactive effects of polygenic risk and cognitive subtype on brain morphology in schizophrenia spectrum and bipolar disorders.

Grey matter volume (GMV) may be associated with polygenic risk for schizophrenia (PRS-SZ) and severe cognitive deficits in people with schizophrenia, schizoaffective disorder (collectively SSD), and bipolar disorder (BD). This study examined the interactive effects of PRS-SZ and cognitive subtypes of SSD and BD in relation to GMV. Two-step cluster analysis was performed on 146 clinical cases (69 SSD and 77 BD) assessed on eight cognitive domains (verbal and visual memory, executive function, processing speed, visual processing, language ability, working memory, and planning). Among them, 55 BD, 51 SSD, and 58 healthy controls (HC), contributed to focal analyses of the relationships between cognitive subtypes, PRS-SZ and their interaction on GMV. Two distinct cognitive subtypes were evident among the combined sample of cases: a 'cognitive deficit' group (CD; N = 31, 20SSD/11BD) showed severe impairment across all cognitive indices, and a 'cognitively spared' (CS; N = 75; 31SSD/44BD) group showed intermediate cognitive performance that was significantly worse than the HC group but better than the CD subgroup. A cognitive subgroup-by-PRS-SZ interaction was significantly associated with GMV in the left precentral gyrus. Moderation analyses revealed a significant negative relationship between PRS-SZ and GMV in the CD group only. At low and average (but not high) PRS-SZ, larger precentral GMV was evident in the CD group compared to both CS and HC groups, and in the CS group compared to HCs. This study provides evidence for a relationship between regional GMV changes and PRS-SZ in psychosis spectrum cases with cognitive deficits, but not in cases cognitively spared.

Increased incidence of childhood mental disorders following exposure to early life infection.

Early life exposure to infectious diseases confers risk for adult psychiatric disorders but relatively few human population studies have examined associations with childhood mental disorder. Here we examined the effects of exposure to maternal infection during pregnancy, and child infectious diseases in early childhood (birth to age 4 years), in relation to first mental disorder diagnosis (age 5-13 years). The study sample comprised 71,841 children represented in a population cohort of children in New South Wales, Australia, followed from birth to early adolescence via linkage of administrative registers. Childhood exposure to infectious disease was determined during the prenatal period (i.e., maternal infection during gestation), and in early childhood (between birth and age 4 years) using the NSW Ministry of Health Admitted Patients data collection. Days to first diagnosis with a mental disorder was determined from recorded diagnoses between age 5-13 years in the NSW Ministry of Health's Admitted Patients, Emergency Department and Mental Health Ambulatory data collections. While crude hazard ratios for both prenatal infection and childhood infection exposures indicated significantly earlier diagnosis with mental disorders associated with both of these risk factors, only childhood infection exposure was associated with higher adjusted hazard ratios (aHR) for any diagnoses (aHR = 1.21, 95% CI = 1.11-1.32), externalising disorders (aHR = 1.45, 95% CI 1.18-1.79) and developmental disorders (aHR = 1.82, 95% CI 1.49-2.22) when the effects of maternal and early childhood (age < 5 years) mental disorders were taken into account. Exposure to infectious diseases during early childhood, but not prenatal infection exposure, appears to be associated with earlier diagnosis of mental disorders in childhood.

The relationship between cortisol reactivity and emotional brain function is differently moderated by childhood trauma, in bipolar disorder, schizophrenia and healthy individuals.

Childhood trauma is a risk factor for psychotic and mood disorders that is associated with abnormal hypothalamic-pituitary-adrenal (HPA) axis function in response to stress and abnormal social brain function. Here, we aimed to determine whether childhood trauma exposure would differently moderate associations between cortisol reactivity and social brain function, among cases with schizophrenia (SZ), bipolar disorder (BD) and in healthy individuals (HC). Forty cases with SZ, 35 with BD and 34 HCs underwent functional magnetic resonance imaging while performing an emotional face-matching task. Participants completed the Childhood Trauma Questionnaire and cortisol reactivity (i.e. the slope indexing the within-subject difference between pre- and post-imaging salivary cortisol levels) was determined. The severity of childhood trauma moderated the relationship between cortisol reactivity and brain activation in the bilateral temporo-parieto-insular junctions, right middle cingulum, right pre/postcentral gyri, left cerebellum and right lingual gyrus, differently depending on the clinical group. When exposed to high levels of trauma, the cortisol slope was negatively associated with activation in these regions in HC, while the cortisol slope was positively associated with activation in these regions in SZ cases. Similarly, there were differences between the groups in how trauma severity moderated the relationship between cortisol reactivity and functional connectivity between the amygdala and dorsolateral prefrontal cortex. In addition to reflecting typical associations between cortisol reactivity and emotional brain function when not exposed to childhood trauma, these findings provide new evidence that trauma exposure disrupts these relationships in both healthy individuals and in cases with SZ or BD.

A Systematic Review of Studies Reporting Data-Driven Cognitive Subtypes across the Psychosis Spectrum.

The delineation of cognitive subtypes of schizophrenia and bipolar disorder may offer a means of determining shared genetic markers and neuropathology among individuals with these conditions. We systematically reviewed the evidence from published studies reporting the use of data-driven (i.e., unsupervised) clustering methods to delineate cognitive subtypes among adults diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. We reviewed 24 studies in total, contributing data to 13 analyses of schizophrenia spectrum patients, 8 analyses of bipolar disorder, and 5 analyses of mixed samples of schizophrenia and bipolar disorder participants. Studies of bipolar disorder most consistently revealed a 3-cluster solution, comprising a subgroup with 'near-normal' (cognitively spared) cognition and two other subgroups demonstrating graded deficits across cognitive domains. In contrast, there was no clear consensus regarding the number of cognitive subtypes among studies of cognitive subtypes in schizophrenia, while four of the five studies of mixed diagnostic groups reported a 4-cluster solution. Common to all cluster solutions was a severe cognitive deficit subtype with cognitive impairments of moderate to large effect size relative to healthy controls. Our review highlights several key factors (e.g., symptom profile, sample size, statistical procedures, and cognitive domains examined) that may influence the results of data-driven clustering methods, and which were largely inconsistent across the studies reviewed. This synthesis of findings suggests caution should be exercised when interpreting the utility of particular cognitive subtypes for biological investigation, and demonstrates much heterogeneity among studies using unsupervised clustering approaches to cognitive subtyping within and across the psychosis spectrum.

Association between childhood trauma exposure and pro-inflammatory cytokines in schizophrenia and bipolar-I disorder.

BACKGROUND: Elevated levels of pro-inflammatory cytokines are consistently reported in schizophrenia (SZ) and bipolar-I disorder (BD), as well as among individuals who have been exposed to childhood trauma. However, higher levels of inflammatory markers in these disorders are yet to be investigated with respect to levels of exposure to different types of childhood trauma. METHODS: Participants were 68 cases with a diagnosis of schizophrenia/schizoaffective disorder (SZ), 69 cases with a diagnosis of psychotic BD and 72 healthy controls (HC). Serum levels of interleukin 6 (IL-6), tumour necrosis factor-α (TNF-α) and C-reactive protein (CRP) were quantified, and childhood trauma exposure was assessed with the Childhood Trauma Questionnaire. RESULTS: The SZ group had significantly higher levels of IL-6, TNF-α and CRP when compared with the HC group (all p < 0.05, d = 0.41-0.63), as well as higher levels of TNF-α when compared with the BD group (p = 0.014, d = 0.50); there were no differences between the BD and HC groups for any markers. Exposure to sexual abuse was positively associated (standardised ß = 0.326, t = 2.459, p = 0.018) with levels of CRP in the SZ group, but there were no significant associations between any form of trauma exposure and cytokine levels in the HC or BD groups. CONCLUSIONS: These results contribute to the evidence for a chronic state of inflammation in SZ but not BD cases. Differential associations between trauma exposure and levels of pro-inflammatory cytokines across the diagnostic categories suggest that trauma may impact biological (stress and immune) systems differently in these patient groups.

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.

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.

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.

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.