The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes. It is still uncertain at what level of the connectome hierarchy differences may exist, and whether they are concentrated in hubs, disrupting fundamental brain connectivity.

We utilized two large cohorts, UK Biobank (UKB, N = 5104) and Generation Scotland (GS, N = 725), to investigate MDD case–control differences in brain network properties. Network analysis was done across four hierarchical levels: (1) global, (2) tier (nodes grouped into four tiers based on degree) and rich club (between-hub connections), (3) nodal, and (4) connection.

In UKB, reductions in network efficiency were observed in MDD cases globally (d = −0.076, pFDR = 0.033), across all tiers (d = −0.069 to −0.079, pFDR = 0.020), and in hubs (d = −0.080 to −0.113, pFDR = 0.013–0.035). No differences in rich club organization and region-to-region connections were identified. The effect sizes and direction for these associations were generally consistent in GS, albeit not significant in our lower-N replication sample.

Our results suggest that the brain's fundamental rich club structure is similar in MDD cases and controls, but subtle topological differences exist across the brain. Consistent with recent large-scale neuroimaging findings, our findings offer a connectomic perspective on a similar scale and support the idea that minimal differences exist between MDD cases and controls.

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.

Lockdown during the pandemic has had significant impacts on public mental health. Previous studies suggest an increase in self-harm and suicide in children and adolescents. There has been little research on the roles of stringent lockdown.

To investigate the mediating and predictive roles of lockdown policy stringency measures in self-harm and emergency psychiatric presentations.

This was a retrospective cohort study. We analysed data of 2073 psychiatric emergency presentations of children and adolescents from 23 hospital catchment areas in ten countries, in March to April 2019 and 2020.

Lockdown measure stringency mediated the reduction in psychiatric emergency presentations (incidence rate ratio of the natural indirect effect [IRRNIE] = 0.41, 95% CI [0.35, 0.48]) and self-harm presentations (IRRNIE = 0.49, 95% CI [0.39, 0.60]) in 2020 compared with 2019. Self-harm presentations among male and looked after children were likely to increase in parallel with lockdown stringency. Self-harm presentations precipitated by social isolation increased with stringency, whereas school pressure and rows with a friend became less likely precipitants. Children from more deprived neighbourhoods were less likely to present to emergency departments when lockdown became more stringent,

Lockdown may produce differential effects among children and adolescents who self-harm. Development in community or remote mental health services is crucial to offset potential barriers to access to emergency psychiatric care, especially for the most deprived youths. Governments should aim to reduce unnecessary fear of help-seeking and keep lockdown as short as possible. Underlying mediation mechanisms of stringent measures and potential psychosocial inequalities warrant further research.

Young adults who are not in employment, education, or training (NEET) are at risk of long-term economic disadvantage and social exclusion. Knowledge about risk factors for being NEET largely comes from cross-sectional studies of vulnerable individuals. Using data collected over a 10-year period, we examined adolescent predictors of being NEET in young adulthood.

We used data on 1938 participants from the Victorian Adolescent Health Cohort Study, a community-based longitudinal study of adolescents in Victoria, Australia. Associations between common mental disorders, disruptive behaviour, cannabis use and drinking behaviour in adolescence, and NEET status at two waves of follow-up in young adulthood (mean ages of 20.7 and 24.1 years) were investigated using logistic regression, with generalised estimating equations used to account for the repeated outcome measure.

Overall, 8.5% of the participants were NEET at age 20.7 years and 8.2% at 24.1 years. After adjusting for potential confounders, we found evidence of increased risk of being NEET among frequent adolescent cannabis users [adjusted odds ratio (ORadj) = 1.74; 95% confidence interval (CI) 1.10–2.75] and those who reported repeated disruptive behaviours (ORadj = 1.71; 95% CI 1.15–2.55) or persistent common mental disorders in adolescence (ORadj = 1.60; 95% CI 1.07–2.40). Similar associations were present when participants with children were included in the same category as those in employment, education, or training.

Young people with an early onset of mental health and behavioural problems are at risk of failing to make the transition from school to employment. This finding reinforces the importance of integrated employment and mental health support programmes.

Previous neuroimaging studies indicate abnormalities in cortico-limbic circuitry in mood disorder. Here we employ prospective longitudinal voxel-based morphometry to examine the trajectory of these abnormalities during early stages of illness development.

Unaffected individuals (16–25 years) at high and low familial risk of mood disorder underwent structural brain imaging on two occasions 2 years apart. Further clinical assessment was conducted 2 years after the second scan (time 3). Clinical outcome data at time 3 was used to categorize individuals: (i) healthy controls (‘low risk’, n = 48); (ii) high-risk individuals who remained well (HR well, n = 53); and (iii) high-risk individuals who developed a major depressive disorder (HR MDD, n = 30). Groups were compared using longitudinal voxel-based morphometry. We also examined whether progress to illness was associated with changes in other potential risk markers (personality traits, symptoms scores and baseline measures of childhood trauma), and whether any changes in brain structure could be indexed using these measures.

Significant decreases in right amygdala grey matter were found in HR MDD v. controls (p = 0.001) and v. HR well (p = 0.005). This structural change was not related to measures of childhood trauma, symptom severity or measures of sub-diagnostic anxiety, neuroticism or extraversion, although cross-sectionally these measures significantly differentiated the groups at baseline.

These longitudinal findings implicate structural amygdala changes in the neurobiology of mood disorder. They also provide a potential biomarker for risk stratification capturing additional information beyond clinically ascertained measures.

Impulsivity is a core feature of borderline personality disorder (BPD) and is most frequently measured using self-rating scales. There is a need to find objective, valid and reliable measures of impulsivity. This study aimed to examine performance of participants with BPD compared with healthy controls on delay and probabilistic discounting tasks and the stop-signal task (SST), which are objective measures of choice and motor impulsivity, respectively.

A total of 20 participants with BPD and 21 healthy control participants completed delay and probabilistic discounting tasks and the SST. They also completed the Barratt Impulsiveness Scale (BIS), a self-rating measure of impulsivity.

Participants with BPD showed significantly greater delay discounting than controls, manifest as a greater tendency to accept the immediately available lesser reward rather than waiting longer for a greater reward. Similarly they showed significantly greater discounting of rewards by the probability of payout, which correlated with past childhood trauma. Participants with BPD were found to choose the more certain and/or immediate rewards, irrespective of the value. On the SST the BPD and control groups did not differ significantly, demonstrating no difference in motor impulsivity. There was no significant difference between groups on self-reported impulsivity as measured by the BIS.

Measures of impulsivity show that while motor impulsivity was not significantly different in participants with BPD compared with controls, choice or reward-related impulsivity was significantly affected in those with BPD. This suggests that choice impulsivity but not motor impulsivity is a core feature of BPD.

Abnormalities of emotion-related brain circuitry, including cortico-thalamic-limbic regions underpin core symptoms of bipolar disorder (BD) and major depressive disorder (MDD). It is unclear whether these abnormalities relate to symptoms of the disorder, are present in unaffected relatives, or whether they can predict future illness.

The Bipolar Family Study (BFS) is a prospective longitudinal study that has examined individuals at familial risk of mood disorder and healthy controls on three occasions, 2 years apart. The current study concerns imaging data from the second assessment; 51 controls and 81 high-risk (HR) individuals performing an emotional memory task. The latter group was divided into 61 HR individuals who were well, and 20 who met diagnostic criteria for MDD. At the time of the third assessment a further 11 HR individuals (from the Well group) had developed MDD. The current analyses focused on (i) differences between groups based on diagnostic status at the time of the scan, and (ii) predictors of future illness, comparing the 11 HR individuals who became unwell after the second scanning assessment to those who remained well.

All groups demonstrated typical emotional modulation of memory and associated brain activations. For analysis (i) the HR MDD group demonstrated increased thalamic activation v. HR Well. (ii) HR Well individuals who subsequently became ill showed increased activation of thalamus, insula and anterior cingulate compared to those who remained well.

These findings suggest evidence for specific changes related to the presence of illness and evidence that changes in brain function in cortico-thalamic-limbic regions precede clinical illness.

The hippocampus plays a central role in memory formation. There is considerable evidence of abnormalities in hippocampal structure and function in schizophrenia, which may differentiate it from bipolar disorder. However, no previous studies have compared hippocampal activation in schizophrenia and bipolar disorder directly.

Fifteen patients with schizophrenia, 14 patients with bipolar disorder and 14 healthy comparison subjects took part in the study. Subjects performed a face–name pair memory task during functional magnetic resonance imaging (fMRI). Differences in blood oxygen level-dependent (BOLD) activity were determined during encoding and retrieval of the face–name pairs.

The patient groups showed significant differences in hippocampal and prefrontal cortex (PFC) activation during face–name pair learning. During encoding, patients with schizophrenia showed decreased anterior hippocampal activation relative to subjects with bipolar disorder, whereas patients with bipolar disorder showed decreased dorsal PFC activation relative to patients with schizophrenia. During retrieval, patients with schizophrenia showed greater activation of the dorsal PFC than patients with bipolar disorder. Patients with schizophrenia also differed from healthy control subjects in the activation of several brain regions, showing impaired superior temporal cortex activation during encoding and greater dorsal PFC activation during retrieval. These effects were evident despite matched task performance.

Patients with schizophrenia showed deficits in hippocampal activation during a memory task relative to patients with bipolar disorder. The disorders were further distinguished by differences in PFC activation. The results demonstrate that these disorders can distinguished at a group level using non-invasive neuroimaging.