Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One possible mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes is via associations with brain structure. This study aimed to elucidate the associations between childhood trauma and brain structure across two large, independent community cohorts.

The two samples comprised (i) a subsample of Generation Scotland (n=1,024); and (ii) individuals from UK Biobank (n=27,202). This comprised n=28,226 for mega-analysis. MRI scans were processed using Free Surfer, providing cortical, subcortical, and global brain metrics. Regression models were used to determine associations between childhood trauma measures and brain metrics and psychiatric phenotypes.

Childhood trauma associated with lifetime depression across cohorts (OR 1.06 GS, 1.23 UKB), and related to early onset and recurrent course within both samples. There was evidence for associations between childhood trauma and structural brain metrics. This included reduced global brain volume, and reduced cortical surface area with highest effects in the frontal (β=−0.0385, SE=0.0048, p(FDR)=5.43x10−15) and parietal lobes (β=−0.0387, SE=0.005, p(FDR)=1.56x10−14). At a regional level the ventral diencephalon (VDc) displayed significant associations with childhood trauma measures across both cohorts and at mega-analysis (β=−0.0232, SE=0.0039, p(FDR)=2.91x10−8). There were also associations with reduced hippocampus, thalamus, and nucleus accumbens volumes.

Associations between childhood trauma and reduced global and regional brain volumes were found, across two independent UK cohorts, and at mega-analysis. This provides robust evidence for a lasting effect of childhood adversity on brain structure.

Major depressive disorder (MDD) was previously associated with negative affective biases. Evidence from larger population-based studies, however, is lacking, including whether biases normalise with remission. We investigated associations between affective bias measures and depressive symptom severity across a large community-based sample, followed by examining differences between remitted individuals and controls.

Participants from Generation Scotland (N = 1109) completed the: (i) Bristol Emotion Recognition Task (BERT), (ii) Face Affective Go/No-go (FAGN), and (iii) Cambridge Gambling Task (CGT). Individuals were classified as MDD-current (n = 43), MDD-remitted (n = 282), or controls (n = 784). Analyses included using affective bias summary measures (primary analyses), followed by detailed emotion/condition analyses of BERT and FAGN (secondary analyses).

For summary measures, the only significant finding was an association between greater symptoms and lower risk adjustment for CGT across the sample (individuals with greater symptoms were less likely to bet more, despite increasingly favourable conditions). This was no longer significant when controlling for non-affective cognition. No differences were found for remitted-MDD v. controls. Detailed analysis of BERT and FAGN indicated subtle negative biases across multiple measures of affective cognition with increasing symptom severity, that were independent of non-effective cognition [e.g. greater tendency to rate faces as angry (BERT), and lower accuracy for happy/neutral conditions (FAGN)]. Results for remitted-MDD were inconsistent.

This suggests the presence of subtle negative affective biases at the level of emotion/condition in association with depressive symptoms across the sample, over and above those accounted for by non-affective cognition, with no evidence for affective biases in remitted individuals.

The COVID-19 pandemic has disrupted lives and livelihoods, and people already experiencing mental ill health may have been especially vulnerable.

Quantify mental health inequalities in disruptions to healthcare, economic activity and housing.

We examined data from 59 482 participants in 12 UK longitudinal studies with data collected before and during the COVID-19 pandemic. Within each study, we estimated the association between psychological distress assessed pre-pandemic and disruptions since the start of the pandemic to healthcare (medication access, procedures or appointments), economic activity (employment, income or working hours) and housing (change of address or household composition). Estimates were pooled across studies.

Across the analysed data-sets, 28% to 77% of participants experienced at least one disruption, with 2.3–33.2% experiencing disruptions in two or more domains. We found 1 s.d. higher pre-pandemic psychological distress was associated with (a) increased odds of any healthcare disruptions (odds ratio (OR) 1.30, 95% CI 1.20–1.40), with fully adjusted odds ratios ranging from 1.24 (95% CI 1.09–1.41) for disruption to procedures to 1.33 (95% CI 1.20–1.49) for disruptions to prescriptions or medication access; (b) loss of employment (odds ratio 1.13, 95% CI 1.06–1.21) and income (OR 1.12, 95% CI 1.06 –1.19), and reductions in working hours/furlough (odds ratio 1.05, 95% CI 1.00–1.09) and (c) increased likelihood of experiencing a disruption in at least two domains (OR 1.25, 95% CI 1.18–1.32) or in one domain (OR 1.11, 95% CI 1.07–1.16), relative to no disruption. There were no associations with housing disruptions (OR 1.00, 95% CI 0.97–1.03).

People experiencing psychological distress pre-pandemic were more likely to experience healthcare and economic disruptions, and clusters of disruptions across multiple domains during the pandemic. Failing to address these disruptions risks further widening mental health inequalities.

The COVID-19 pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences.

To quantify the prevalence of depression, anxiety and mental well-being before and during the COVID-19 pandemic. Also, to identify groups at risk of depression and/or anxiety during the pandemic.

Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) index generation (n = 2850, mean age 28 years) and parent generation (n = 3720, mean age 59 years), and Generation Scotland (n = 4233, mean age 59 years). Depression was measured with the Short Mood and Feelings Questionnaire in ALSPAC and the Patient Health Questionnaire-9 in Generation Scotland. Anxiety and mental well-being were measured with the Generalised Anxiety Disorder Assessment-7 and the Short Warwick Edinburgh Mental Wellbeing Scale.

Depression during the pandemic was similar to pre-pandemic levels in the ALSPAC index generation, but those experiencing anxiety had almost doubled, at 24% (95% CI 23–26%) compared with a pre-pandemic level of 13% (95% CI 12–14%). In both studies, anxiety and depression during the pandemic was greater in younger members, women, those with pre-existing mental/physical health conditions and individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression.

These results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during the COVID-19 pandemic. This is important for planning current mental health provisions and for long-term impact beyond this pandemic.

Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.

We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.

In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).

AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.

Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.

We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.

We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.

Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.

Objective: Deficits in adult and embryonic neurogenesis have been linked with neurological and psychiatric disorders, so it is important to understand the molecular mechanisms underlying this process. SOX11 is a transcription factor known to play a critical role in the regulation of the neuronal and glial differentiation stage of neurogenesis, so we hypothesised that the identification of its target genes would reveal underlying biological processes relevant to disease.

Methods: SOX11 protein was over-expressed in HEK293 cells and transcriptional changes assessed by microarray analysis. Selected candidate genes were further tested for SOX11 activation in quantitative reverse transcriptase PCR studies of HEK293 cells and Western analysis of SH-SY5Y cells.

Results: Regulated genes included a previously established SOX11 target, known markers of neurogenesis, as well as several genes implicated in neuropsychiatric disorders. Immunofluorescence localised several of the genes within the proliferative subgranular zone of the hippocampus. We observed multiple histone and zinc finger genes regulated by SOX11, many of which were located in two clusters on chromosomes 6 and 19. The chromosome 6 cluster lies within a region of the genome showing the strongest genetic association with schizophrenia.

Conclusion: SOX11 appears to regulate a complex programme of chromatin remodelling and downstream gene expression changes to achieve a mature neuronal phenotype. SOX11 target genes are shown to be involved in neurodevelopmental processes important in health and, potentially, disease.