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.

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.

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.

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.

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 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.

Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder.

Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors impact the development of psychopathology within the context of elevated genetic risk is unknown. We herein sought to identify epigenetic signatures operating in the context of polygenic risk for BD in young people at high familial risk (HR) of BD. Peripheral blood-derived DNA was assayed using Illumina PsychArray, and Methylation-450K or -EPIC BeadChips.

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).

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).

Familial clustering of birth risk for adverse childhood outcomes.

Objective: To identify classes of children exposed to distinct clusters of perinatal and familial risk factors at the time of birth, and examine relationships between class membership and a variety of adverse outcomes in childhood.

Design: A prospective longitudinal study of children (and their parents) born between 2002 and 2004 and who have been followed-up until 12-13 years of age. A combination of latent class analysis and logistic regression analyses were used.

Schizotypy, childhood trauma and brain morphometry.

Background: Childhood trauma confers risk for psychosis and is associated with increased 'schizotypy' (a multi-dimensional construct reflecting risk for psychosis in the general population). Structural brain alterations are associated with both childhood trauma and schizotypy, but the potential role of trauma exposure in moderating associations between schizotypy and brain morphology has yet to be determined.

Methods: Participants were 160 healthy individuals (mean age: 40.

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.

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.

Systemic inflammation and grey matter volume in schizophrenia and bipolar disorder: Moderation by childhood trauma severity.

Background: Elevated levels of systemic inflammation are consistently reported in both schizophrenia (SZ) and bipolar-I disorder (BD), and are associated with childhood trauma exposure. We tested whether childhood trauma exposure moderates associations between systemic inflammation and brain morphology in people with these diagnoses.

Methods: Participants were 55 SZ cases, 52 BD cases and 59 healthy controls (HC) who underwent magnetic resonance imaging.

Derivation of poly-methylomic profile scores for schizophrenia.

Schizophrenia and bipolar disorder share biological features and environmental risk factors that may be associated with altered DNA methylation. In this study we sought to: 1) construct a novel 'Poly-Methylomic Profile Score (PMPS)' by transforming schizophrenia-associated epigenome-wide methylation from a previously published epigenome-wide association study (EWAS) into a single quantitative metric; and 2) examine associations between the PMPS and clinical status in an independent sample of 57 schizophrenia (SZ) cases, 59 bipolar disorder (BD) cases and 55 healthy controls (HC) for whom blood-derived DNA methylation was quantified using the Illumina 450 K methylation beadchip. We constructed five PMPSs at different p-value thresholds by summing methylation beta-values weighted by individual-CpG effect sizes from the meta-analysis of a previously published schizophrenia EWAS (comprising three separate cohorts with 675 [353 SZ and 322 HC] discovery cohort participants, 847 [414 SZ and 433 HC] replication cohort participants, and 96 monozygotic twin-pairs discordant for SZ).

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).

Glucocorticoid receptor gene (NR3C1) DNA methylation in association with trauma, psychopathology, transcript expression, or genotypic variation: A systematic review.

The glucocorticoid receptor gene (NR3C1) is a critical component of the stress response system. Cytosine methylation of NR3C1 has been repeatedly associated with trauma and mental disorders, including major depression, post-traumatic stress disorder, anxiety, and personality disorders, suggesting that NR3C1 methylation may play a role in stress-related psychopathology. We systematically reviewed 55 studies examining NR3C1 DNA methylation in association with trauma exposure, psychopathology, gene expression, and/or common genetic variants.