Neuroticism, a personality trait linked to both cardiovascular and psychiatric disorders, has been associated with cognitive decline and increased dementia risk, though the underlying neural mechanisms remain unclear. Mapping its relationship with brain structure could provide valuable insights into neural pathways and targets for early intervention.

We examined brain-wide associations between neuroticism and structural neuroimaging metrics derived from T1-, T2-weighted, and diffusion MRI in 36,901 dementia-free UK Biobank participants. Bonferroni-significant associations underwent bidirectional two-sample Mendelian randomization to evaluate the evidence for a causal relationship. Given that neuroticism is generally stable across adulthood and challenging to modify, we assessed whether these associations were mediated by health conditions (depression, anxiety, hypertension, ischemic heart disease [IHD], and diabetes) that are both consequences of neuroticism and known risk factors for dementia, and also modifiable through widely available and efficacious therapeutic interventions.

Higher neuroticism was found to be associated with reduced grey matter volumes in the frontal and limbic regions, as well as widespread differences in white matter microstructure, particularly in thalamic radiations. Genetic analyses supported a potential causal effect of neuroticism on increased diffusivity in thalamic radiations. Hypertension mediated the associations between neuroticism and both grey and white matter measures, while depression and anxiety primarily mediated associations with white matter microstructure. Contributions from IHD and diabetes were minimal.

Neuroticism is linked to widespread structural brain differences that contribute to poorer brain health, and targeting vascular and mental health may help mitigate its impact.

Childhood maltreatment is a robust predictor of aggression. Research indicates that both maltreatment experiences and aggression are moderately heritable. It has been hypothesized that gene–environment correlation may be at play, whereby genetic predispositions to aggression in parents and children may be confounded with family environments conducive to its expression. Building on this framework, we tested whether maltreatment mediates the association between a polygenic score for aggression (PGSAGG) and school-age aggression, and whether this varied for reactive and proactive aggression.

The sample comprised 721 participants (44.9% males; 99.0% White) with prospective assessments of maltreatment from 5 months to 12 years (10 assessments;1998–2010), and teachers-reported aggression from ages 6 to 13 (6 assessments; 2004–2011). The PGSAGG was derived using a Bayesian estimation method (PRS-CS).

PGSAGG was associated with most aggression measures across specific ages and trajectories. Maltreatment experiences partially mediated the association between PGSAGG and the Childhood-Limited trajectory of reactive – but not proactive – aggression.

Children with higher genetic propensities for aggression were more likely to experience maltreatment, which partly explained the association between PGSAGG and a Childhood-Limited trajectory of reactive aggression during elementary school. This finding reinforces the possibility of confounding influences between genetic liability for aggression and maltreatment experiences.

Although global knowledge on paediatric cardiomyopathies has advanced, prospective cohort studies from Brazil, particularly those integrating clinical and genetic data, remain limited.

To describe the clinical and genetic characteristics of paediatric cardiomyopathy patients and identify mortality predictors in a metropolitan region of Brazil.

Prospective observational study of paediatric patients with cardiomyopathies. Clinical data, genetic findings, and survival were analysed using Kaplan–Meier curves.

A total of 45 cases, male predominance (55.6%), and mean age at diagnosis of 6.5 years. Dilated and hypertrophic cardiomyopathy were the most common (33.3%). The main reason for diagnosis was the investigation of cardiovascular symptoms (60.9%). Genetic investigation occurred in 66.6%, a positivity rate of 60%. Multi-organ/system involvement was significantly associated with a positive genetic result (77.7%, p = 0.017). Mortality was 11.1%; survival was significantly lower in the following conditions: ejection fraction < 30% (p < 0.0001), functional class III/IV (p < 0.0001), heart failure (p = 0.0091), use of three or more cardiovascular medications (p < 0.001), N-Terminal Pro-B-Type natriuretic peptide >1000pg/mL (p = 0.004), and heart transplant indication (p < 0.001).

These findings provide novel data in Brazil, highlight a high rate of positive genetic test, particularly among patients with systemic involvement and identify key clinical predictors of mortality to guide risk stratification and care.

Some psychotic experiences in the general population show associations with higher schizophrenia and other mental health-related polygenic risk scores (PRSs), but studies have not usually included interviewer-rated positive, negative and disorganised dimensions, which show distinct associations in clinical samples.

To investigate associations of these psychotic experience dimensions primarily with schizophrenia PRS and, secondarily, with other relevant PRSs.

Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort participants were assessed for positive, negative and disorganised psychotic experience dimensions from interviews, and for self-rated negative symptoms, at 24 years of age. Regression models were used to investigate associations between psychotic experience dimensions and schizophrenia and other PRSs (2500+ participants for each analysis).

Against expectation, none of the positive, negative or disorganised dimensions was associated with schizophrenia PRS. In secondary analysis, self-rated negative symptoms were associated with higher depression (β = 0.10 [95% CI 0.06–0.15]), anxiety (β = 0.09 [95% CI 0.04–0.13]), neuroticism (β = 0.11 [95% CI 0.06–0.15]) and autism (β = 0.09 [95% CI 0.05–0.13]) PRSs (all P < 0.001); and first-rank delusions were nominally associated with higher schizophrenia PRS (odds ratio 7.35 [95% CI 2.10–25.77], P = 0.002), although these experiences/symptoms were rare.

Positive, negative and disorganised psychotic experiences are probably not strongly associated with polygenic liability to schizophrenia in this general population cohort of young adults. Self-rated negative symptoms may indicate social withdrawal/low motivation due to higher polygenic liability to affective disorders or autism, and first-rank delusions may indicate higher polygenic liability to schizophrenia, but these findings require independent confirmation.

During puberty, sex-specific processes shape distinct mental health outcomes. However, research on puberty and psychosis has been limited, and the findings are conflicting.

To explore how puberty status and timing and oestradiol levels influence psychotic experiences and whether they interact with genetic and exposomic vulnerabilities to schizophrenia in female adolescents.

We analysed data from female participants in the Adolescent Brain Cognitive Development Study at baseline (n = 5673) and two annual follow-up assessments. Psychotic experiences were assessed using the Prodromal Psychosis Scale and puberty status with the Pubertal Development Scale. Age at menarche and salivary oestradiol concentration were recorded. Exposomic vulnerability to schizophrenia (ES-SCZ) and polygenic risk score for schizophrenia (PRS-SCZ) were calculated. Longitudinal mixed logistic regression models were used to test associations of psychotic experiences with hormone levels and puberty status. Age of menarche was analysed using second follow-up data.

Earlier menarche (odds ratio 0.68, 95% CI: 0.59 to 0.78) and higher oestradiol concentration (odds ratio = 1.08, 95% CI: 1.01 to 1.16) were associated with greater likelihood of psychotic experiences, as were mid-pubertal (odds ratio 1.41, 95% CI: 1.18 to 1.69) and late to post-pubertal (odds ratio 2.23, 95% CI: 1.74 to 2.86) compared with pre-pubertal stage. ES-SCZ and PRS-SCZ were associated with greater likelihood of psychotic experiences. No significant interactions of puberty factors with ES-SCZ or PRS-SCZ were detected.

Physical and hormonal puberty factors have critical roles in development of psychosis. The absence of interaction effects could be attributed to the age range of the cohort. Further research during follow-ups is essential.

There is growing evidence that smoking increases the risk of developing psychiatric disorders, but the underlying mechanisms are largely unknown. We examine brain structure as a potential pathway between smoking and psychiatric disease liability.

We test associations between smoking (initiation, cigarettes per day, cessation, lifetime use) and depression, bipolar disorder, and schizophrenia, with and without correcting for volume of the amygdala, hippocampus, lateral and medial orbitofrontal cortex, superior frontal context, and cortical thickness and surface area. We use three methods that use summary statistics of genome-wide association studies to investigate genome-wide and local genetic overlap (genomic structural equation modeling, local analysis of (co)variant association), as well as causal associations (Mendelian randomization).

While we find causal effects of smoking on brain volume in different brain areas, and with psychiatric disorders, brain volume did not seem to mediate the effect of smoking on psychiatric disorders.

While these findings are limited by characteristics of the included summary statistics (e.g. sample size), we conclude that brain volume of these areas is unlikely to explain a substantial part of any effect of smoking on psychiatric disorders. Nevertheless, genetic methods are valuable tools for exploring other potential mechanisms, such as brain functional connectivity, foregoing the need to collect all phenotypes in one dataset.