Childhood adversity is associated with increased later mental health problems and suicidal behaviour. Opportunities for earlier healthcare identification and intervention are needed.

To determine associations between hospital admissions for childhood adversity and mental health in children who later die by suicide.

Population-based longitudinal case-control study. Scottish in-patient general and psychiatric records were summarised for individuals born 1981 or later who died by suicide between 1991 and 2017 (cases), and matched controls (1:10), for childhood adversity and mental health (broadly defined as psychiatric diagnoses and general hospital admissions for self-harm and substance use).

Records were extracted for 2477 ‘cases’ and 24 777 ‘controls’; 2106 cases (85%) and 13 589 controls (55%) had lifespan hospitalisations. Mean age at death was 23.7; 75.9% were male. Maltreatment or violence-related childhood adversity codes were recorded for 7.6% cases aged 10–17 (160/2106) versus 2.7% controls (371/13 589), odds ratio = 2.9 (95% CI, 2.4–3.6); mental health-related admissions were recorded for 21.7% cases (458/2106), versus 4.1% controls (560/13 589), odds ratio = 6.5 (95% CI, 5.7–7.4); 80% of mental health admissions were in general hospitals. Using conditional logistic models, we found a dose-response effect of mental health admissions <18y, with highest adjusted odds ratio (aOR) for three or more mental health admissions: aORmale = 8.17 (95% CI, 5.02–13.29), aORfemale = 15.08 (95% CI, 8.07–28.17). We estimated that each type of childhood adversity multiplied odds of suicide by aORmale = 1.90 (95% CI, 1.64–2.21), aORfemale = 2.65 (95% CI, 1.94–3.62), and each mental health admission by aORmale = 2.06 (95% CI, 1.81–2.34), aORfemale = 1.78 (95% CI, 1.50–2.10).

Our lifespan study found that experiencing childhood adversity (primarily maltreatment or violence-related admissions) or mental health admissions increased odds of young person suicide, with highest odds for those experiencing both. Healthcare practitioners should identify and flag potential ‘at-risk’ adolescents to prevent future suicidal acts, especially those in general hospitals.

Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood.

Two hundred and forty-three patients were assessed at their first episode of psychosis for CA and re-assessed after a mean of 21 years of follow-up for several outcome domains, including symptoms, functioning, quality of life, cognitive performance, neurological dysfunction, and comorbidity. The unique predictive ability of CA exposure for outcomes was examined using linear regression analysis controlling for relevant confounders, including socioeconomic status, family risk of schizophrenia, and obstetric complications.

There were 54% of the patients with a documented history of CA at mild or higher levels. CA experiences were more prevalent and severe in schizophrenia than in other psychotic disorders (p < 0.001). Large to very large effect sizes were observed for CA predicting most role functioning variables and negative symptoms (ΔR2 between 0.105 and 0.181). Moderate effect sizes were observed for positive symptoms, personal functioning, impaired social cognition, impaired immediate verbal learning, poor global cognition, internalized stigma, poor personal recovery, and drug abuse severity (ΔR2 between 0.040 and 0.066). A dose–response relationship was observed between levels of CA and severity of outcome domains.

Our results suggest a strong and widespread link between early adversity exposure and outcomes of psychotic disorders. Awareness of the serious long-term consequences of CA should encourage better identification of those at risk and the development of effective interventions.

The neuroanatomical alteration in bipolar II depression (BDII-D) and its associations with inflammation, childhood adversity, and psychiatric symptoms are currently unclear. We hypothesize that neuroanatomical deficits will be related to higher inflammation, greater childhood adversity, and worse psychiatric symptoms in BDII-D.

Voxel- and surface-based morphometry was performed using the CAT toolbox in 150 BDII-D patients and 155 healthy controls (HCs). Partial Pearson correlations followed by multiple comparison correction was used to indicate significant relationships between neuroanatomy and inflammation, childhood adversity, and psychiatric symptoms.

Compared with HCs, the BDII-D group demonstrated significantly smaller gray matter volumes (GMVs) in frontostriatal and fronto-cerebellar area, insula, rectus, and temporal gyrus, while significantly thinner cortices were found in frontal and temporal areas. In BDII-D, smaller GMV in the right middle frontal gyrus (MFG) was correlated with greater sexual abuse (r = −0.348, q < 0.001) while larger GMV in the right orbital MFG was correlated with greater physical neglect (r = 0.254, q = 0.03). Higher WBC count (r = −0.227, q = 0.015) and IL-6 levels (r = −0.266, q = 0.015) was associated with smaller GMVs in fronto-cerebellar area in BDII-D. Greater positive symptoms was correlated with larger GMVs of the left middle temporal pole (r = 0.245, q = 0.03).

Neuroanatomical alterations in frontostriatal and fronto-cerebellar area, insula, rectus, temporal gyrus volumes, and frontal-temporal thickness may reflect a core pathophysiological mechanism of BDII-D, which are related to inflammation, trauma, and psychiatric symptoms in BDII-D.

Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms.

We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT1A) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT1A receptor binding potential (BPF) determined by positron emission tomography (PET) in 13 a priori brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls).

Medication-free participants with MDD (n = 192: 110 female, 81 male, 1 other) and controls (n = 88: 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295. DNA methylation was assayed at three upstream promoter sites (−1019, −1007, −681) of the 5-HT1A receptor gene. A subgroup (n = 119) had regional brain 5-HT1A receptor BPF quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BPF.

Recent stress correlated positively with blood monocyte methylation at the −681 CpG site, adjusted for diagnosis, and had positive and region-specific correlations with 5-HT1A BPF in participants with MDD, but not in controls. In participants with MDD, but not in controls, methylation at the −1007 CpG site had positive and region-specific correlations with binding potential. Childhood adversity was not associated with methylation or BPF in participants with MDD.

These findings support a model in which recent stress increases 5-HT1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.

Despite the growing interest in addiction research, which demonstrates the potential predictive role of adverse childhood experiences (ACEs), little is known about their impact on the psychological symptoms of craving.

After reviewing the relevant diagnostic criteria for addiction and comorbid mental disorders along with routinely collected clinical and service-use data, 208 outpatients were assessed on the study protocol. Following the recruitment phase, nominal and ordinal data were analyzed using nonparametric methods.

Most of the outpatients reported ACEs (89.1%) and experienced cravings (73.4–95.7%). A positive association between ACEs and either intention and preplanning (r = .14, p < .05) or lack of control (r = .15; p < .05) of the craving behavior was found.

Craving behavior in addiction remains a subject of debate. Although correlation analyses showed significant associations between reported ACEs and measures of craving, they were relatively small.

The aetiology of dual harm (co-occurring self-harm and violence towards others) is poorly understood because most studies have investigated self-harm and violence separately. We aimed to examine childhood risk factors for self-harm, violence, and dual harm, including the transition from engaging in single harm to dual harm.

Data from the Avon Longitudinal Study of Parents and Children, a UK-based birth cohort study, were used to estimate prevalence of self-reported engagement in self-harm, violence, and dual harm at ages 16 and 22 years. Risk ratios were calculated to indicate associations across various self-reported childhood risk factors and risks of single and dual harm, including the transition from single harm at age 16 years to dual harm at age 22.

At age 16 years, 18.1% of the 4176 cohort members had harmed themselves, 21.1% had engaged in violence towards others and 3.7% reported dual harm. At age 22 the equivalent prevalence estimates increased to 24.2, 25.8 and 6.8%, respectively. Depression and other mental health difficulties, drug and alcohol use, witnessing self-harm and being a victim of, or witnessing, violence were associated with higher risks of transitioning from self-harm or violence at age 16 to dual harm by age 22.

Prevalence of dual harm doubled from age 16 to 22 years, highlighting the importance of early identification and intervention during this high-risk period. Several childhood psychosocial risk factors associated specifically with dual harm at age 16 and with the transition to dual harm by age 22 have been identified.

Reported childhood adversity (CA) is associated with development of depression in adulthood and predicts a more severe course of illness. Although elevated serotonin 1A receptor (5-HT1AR) binding potential, especially in the raphe nuclei, has been shown to be a trait associated with major depression, we did not replicate this finding in an independent sample using the partial agonist positron emission tomography tracer [11C]CUMI-101. Evidence suggests that CA can induce long-lasting changes in expression of 5-HT1AR, and thus, a history of CA may explain the disparate findings.

Following up on our initial report, 28 unmedicated participants in a current depressive episode (bipolar n = 16, unipolar n = 12) and 19 non-depressed healthy volunteers (HVs) underwent [11C]CUMI-101 imaging to quantify 5-HT1AR binding potential. Participants in a depressive episode were stratified into mild/moderate and severe CA groups via the Childhood Trauma Questionnaire. We hypothesized higher hippocampal and raphe nuclei 5-HT1AR with severe CA compared with mild/moderate CA and HVs.

There was a group-by-region effect (p = 0.011) when considering HV, depressive episode mild/moderate CA, and depressive episode severe CA groups, driven by significantly higher hippocampal 5-HT1AR binding potential in participants in a depressive episode with severe CA relative to HVs (p = 0.019). Contrary to our hypothesis, no significant binding potential differences were detected in the raphe nuclei (p-values > 0.05).

With replication in larger samples, elevated hippocampal 5-HT1AR binding potential may serve as a promising biomarker through which to investigate the neurobiological link between CA and depression.

Stress caused by childhood adversity (CA) is known to contribute to schizophrenia risk and symptoms. Its effects might be mediated by epigenetic mechanisms, specifically DNA methylation (meDNA) within relevant genes, and predominantly influence the hippocampus and prefrontal cortex (PFC). CYP17A1 is a candidate, as it situates within a schizophrenia risk locus and is involved in glucocorticoid synthesis.

To explore meDNA within CYP17A and its relations to hippocampus- and PFC-dependent schizophrenia symptoms: depression and deficits of declarative memory and executive functions.

We assessed meDNA at each CpG within a CYP17A fragment (chr10:104594471-104595887, hg19) in blood of 66 schizophrenia patients using the third-generation sequencing. Immediate memory, depression, cognitive shifting and cognitive inhibition (CI) were assessed with the RAVLT, PANSS, TMT-B and Stroop word-color test, respectively. ANCOVA and regression models adjusted for sex and age were applied to explore the relations between the phenotypes, local haplotype, meDNA and CA, defined as the presence of parental alcoholism or psychiatric illness.

MeDNA at CpG-SNP rs3781286 correlated with CI (corrected p=0.01). However, there were no main or interaction effects of CA either on meDNA at this site or on CI. Both CI and meDNA associated with haplotype, but subsequent analysis showed that meDNA did not mediate the relation between haplotype and CI.

Our findings suggest that CYP17A associates with PFC-dependent cognitive deficits in schizophrenia but did not support the hypothesis that CA plays a role in this association via meDNA or any other mechanism. Grant support: 21-15-00124/Russian Science Foundation https://rscf.ru/project/21-15-00124/.

No significant relationships.

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.

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.

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.

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.

Psychotic experiences (PEs) are relatively common in childhood and adolescence and are associated with increased risk of functional issues and psychiatric illness in young adulthood, and PEs that recur are associated with increased risk of poorer psychiatric and functional outcomes. Childhood adversity is a well-established risk factor for PEs. The aim of this study was to investigate (1) the relationship between childhood adversity and recurring PEs in adolescence and (2) candidate mediators of that relationship.

We used data from Cohort ‘98 of the Growing Up in Ireland study (n = 6039) at three time points (ages 9, 13 and 17) to investigate the relationship between childhood adversity (parent-reported at age 9), recurring PEs (measured using a subset of the Adolescent Psychotic-like Symptoms Screener at ages 13 and 17). The mediating roles of parent–child relationship, internalising and externalising difficulties, self-concept, physical activity, dietary quality, perceived neighbourhood safety and friendship quantity were investigated using the KHB path decomposition method.

Childhood adversity was associated with an increased risk of recurring PEs with a population attributable fraction of 23%. Internalising difficulties and self-concept explained 13% of the relationship between childhood adversity and PEs suggesting a partial mediation. A significant direct effect remained between childhood adversity and recurring PEs.

The established relationship between childhood adversity and PEs may be mainly driven by the relationship between childhood adversity and recurring PEs. Internalising difficulties and self-concept together mediate part of the relationship between childhood adversity and recurring PEs.

Little is known about the childhood antecedents and adult correlates of adolescent dual-harm (i.e. co-occurring self- and other-harm). We examine the longitudinal associations between (a) social and psychological risk factors in childhood and adolescent dual-harm and (b) adolescent dual-harm and social and mental health impairments in early adulthood.

Participants (N = 1482) are from a prospective longitudinal community-representative study. Dual-, self-, and other-harm were self-reported at ages 13, 15, and 17. Social and psychological risk factors in childhood were assessed between 7 and 11; early adult correlates at age 20. Groups with dual-harm, self-harm only, other-harm only, and no harm were compared.

Between 13 and 17, 7.2% of adolescents reported dual-harm (self-harm only: 16.2%; other-harm only: 13.3%). Some childhood risk factors (e.g. sensation-seeking, parental divorce, victimization by peers) characterized all harm groups; others were common to the dual- and self-harm (anxiety/depressive symptoms, relational aggression) or dual- and other-harm groups only (low self-control, substance use, delinquency). Adolescents with dual-harm had reported more physical aggression and harsh parenting, and lower school bonding in childhood than any other group. In early adulthood, they reported more anxiety/depressive symptoms, psychopathy symptoms, homicidal ideations, delinquency, and victimization experiences than any other group.

Adolescent dual-harm follows psychological problems and social disconnection in childhood and signals risk of psychopathology and isolation in early adulthood. To curb the burden from dual-harm, interventions must target adolescents, families, peer networks, and school environments. Differentiating youth with dual-harm from those with single-harm is important for developing personalized treatments.