Trauma is prevalent amongst early psychosis patients and associated with adverse outcomes. Past trials of trauma-focused therapy have focused on chronic patients with psychosis/schizophrenia and comorbid Post-Traumatic Stress Disorder (PTSD). We aimed to determine the feasibility of a large-scale randomized controlled trial (RCT) of an Eye Movement Desensitization and Reprocessing for psychosis (EMDRp) intervention for early psychosis service users.

A single-blind RCT comparing 16 sessions of EMDRp + TAU v. TAU only was conducted. Participants completed baseline, 6-month and 12-month post-randomization assessments. EMDRp and trial assessments were delivered both in-person and remotely due to COVID-19 restrictions. Feasibility outcomes were recruitment and retention, therapy attendance/engagement, adherence to EMDRp treatment protocol, and the ‘promise of efficacy’ of EMDRp on relevant clinical outcomes.

Sixty participants (100% of the recruitment target) received TAU or EMDR + TAU. 83% completed at least one follow-up assessment, with 74% at 6-month and 70% at 12-month. 74% of EMDRp + TAU participants received at least eight therapy sessions and 97% rated therapy sessions demonstrated good treatment fidelity. At 6-month, there were signals of promise of efficacy of EMDRp + TAU v. TAU for total psychotic symptoms (PANSS), subjective recovery from psychosis, PTSD symptoms, depression, anxiety, and general health status. Signals of efficacy at 12-month were less pronounced but remained robust for PTSD symptoms and general health status.

The trial feasibility criteria were fully met, and EMDRp was associated with promising signals of efficacy on a range of valuable clinical outcomes. A larger-scale, multi-center trial of EMDRp is feasible and warranted.

The DSM-5 features hundreds of diagnoses comprising a multitude of symptoms, and there is considerable repetition in the symptoms among diagnoses. This repetition undermines what we can learn from studying individual diagnostic constructs because it can obscure both disorder- and symptom-specific signals. However, these lost opportunities are currently veiled because symptom repetition in the DSM-5 has not been quantified.

This descriptive study mapped the repetition among the 1419 symptoms described in 202 diagnoses of adult psychopathology in section II of the DSM-5. Over a million possible symptom comparisons needed to be conducted, for which we used both qualitative content coding and natural language processing.

In total, we identified 628 distinct symptoms: 397 symptoms (63.2%) were unique to a single diagnosis, whereas 231 symptoms (36.8%) repeated across multiple diagnoses a total of 1022 times (median 3 times per symptom; range 2–22). Some chapters had more repetition than others: For example, every symptom of every diagnosis in the bipolar and related disorders chapter was repeated in other chapters, but there was no repetition for any symptoms of any diagnoses in the elimination disorders, gender dysphoria or paraphilic disorders. The most frequently repeated symptoms included insomnia, difficulty concentrating, and irritability – listed in 22, 17 and 16 diagnoses, respectively. Notably, the top 15 most frequently repeating diagnostic criteria were dominated by symptoms of major depressive disorder.

Overall, our findings lay the foundation for a better understanding of the extent and potential consequences of symptom overlap.

Cross-sectional studies report high levels of depressive symptoms during the COVID-19 pandemic, especially in youth and females. However, longitudinal research comparing depressive symptoms before and during the pandemic is lacking. Little is known about how the pandemic affected individuals with familial history of mental illness. The present study examines the impact of the pandemic on youth depressive symptoms, including offspring of parents with major mood and psychotic disorders.

Between March 2018 and February 2020, we measured depressive symptoms in 412 youth aged 5–25 years. We measured depressive symptoms again in 371 (90%) of these youth between April 2020 and May 2022. Two thirds (249) participants had a biological parent with a major mood or psychotic disorder. We tested the effect of the pandemic by comparing depression symptoms before and after March 2020. We examined age, sex, and family history as potential moderators.

We found an overall small increase in youth depressive symptoms (b = 0.07, 95% CI −0.01 to 0.15, p = 0.062). This was driven by an increase in female youth without familial history of mental illness (b = 0.35, 95% CI 0.14 to 0.56, p = 0.001). There was no change in depressive symptoms among offspring of parents with mental illness or males.

Our results provide reassurance about the wellbeing of children of parents with mental illness during a period of restricted access to resources outside the family. Rather than increasing symptoms in established risk groups, the pandemic led to a redistribution of depression burden towards segments of the youth population that were previously considered to be low-risk.

There are many barriers to engaging in current psychological treatments, including time, cost, and availability. Ultra-brief treatments overcome some of these barriers by delivering therapeutic information and skills using significantly less time than standard-length treatments. We developed a therapist-guided online ultra-brief treatment for depression and anxiety and compared it to an existing 8-week, 5-lesson therapist-guided standard-length treatment and a waitlist control.

In a randomized controlled trial, adults with self-reported depression or anxiety were randomized (1:1:1) to the ultra-brief treatment, standard-length treatment, or waitlist control. The primary outcomes were depression symptoms and anxiety symptoms assessed at baseline, 5-weeks later, 9-weeks later (primary timepoint), and 3-months later. The trial was prospectively registered.

Between 7 February 2022, and 16 August 2022, 242 participants were enrolled in the ultra-brief treatment (n = 85), standard-length treatment (n = 80), and waitlist control (n = 77). Participants were mostly women with an average age of 48.56 years. At 9-weeks post-baseline, participants in the ultra-brief treatment group reported significantly lower depression (between groups d = 0.41) and anxiety (d = 0.53) than the waitlist control. The ultra-brief treatment was non-inferior for anxiety at both 9-weeks and 3-months follow-up. Non-inferiority for depression was observed at 9-weeks.

The online ultra-brief treatment resulted in significant reductions in depression and anxiety that were non-inferior to a longer treatment course after 9-weeks. Remotely delivered ultra-brief treatments have the potential to provide accessible and effective care for those who cannot, or would prefer not to, access longer psychological interventions.

Individuals with schizophrenia spectrum and related psychotic disorders (SSD) experience significant impairments in social cognition that impede functioning. Social cognition is a multidimensional construct consisting of four domains: 1. theory of mind, 2. emotion processing, 3. attributional style and 4. social perception. Metacognitive training (MCT) is an intervention designed to target cognitive biases in psychosis containing two modules addressing social cognition.

A systematic review and meta-analysis was conducted to investigate the effects of MCT on social cognition and two of its domains: theory of mind and emotion processing. Ten electronic databases were scoured from 2007 to 1 February 2022 for MCT studies reporting social cognition outcomes for people with SSD (1050 identified, 282 assessed). Effect sizes were calculated using Cohen's d in R.

Nine studies were included in the meta-analysis (nMCT = 212, ncontrol = 194). MCT had a small but positive effect on global social cognition (d = 0.28 [95% CI 0.07–0.49]) and theory of mind (d = 0.27 [95% CI 0.01–0.52]). MCT showed no evidence of an effect on emotion processing (d = 0.03 [95% CI –0.26 to 0.32]).

MCT has a small but significant effect on social cognition for people with SSD. Our results add to other recent meta-analyses showing significant effects of MCT on clinically relevant outcomes such as positive symptoms, cognitive biases and cognitive insight. We recommend that future studies on MCT report outcomes on all four domains of social cognition.

PROSPERO (in the process of registration) available at https://www.crd.york.ac.uk/prospero/#recordDetails

Little information is available on the association between gender nonconformity during adolescence and subsequent mental health. While the distress related to gender nonconformity may be socially produced rather than attributed to individual-level factors, further research is needed to better understand the role of psychosocial factors in this context.

We analyzed data from the Tokyo Teen Cohort, obtained through random sampling of adolescents born between 2002 and 2004. We used inverse probability weighting to examine the association of gender nonconformity at ages 12 and 14 as a time-varying variable with subsequent mental health at age 16, while accounting for time-fixed and time-varying confounders. Furthermore, we used a weighting approach to investigate the mediating role of modifiable psychosocial factors in this association, addressing exposure-mediator and mediator–mediator interactions.

A total of 3171 participants were analyzed. Persistent gender nonconforming behavior at ages 12 and 14 was associated with subsequent depression (β = 2.02, 95% confidence interval [CI] 0.85 to 3.19) and psychotic experiences (β = 0.33, 95% CI 0.14 to 0.52) at age 16. The results remained robust in sensitivity analyses. Approximately 30% of the association between gender nonconformity and depression was consistently mediated by a set of psychosocial factors, namely loneliness, bullying victimization, and relationships with mother, father, and friends.

Persistent gender nonconformity during adolescence is associated with subsequent mental health. Psychosocial factors play a vital mediating role in this association, highlighting the essential need for social intervention and change to reduce stigmatization and ameliorate mental health challenges.

Individuals with serious mental illness have a markedly shorter life expectancy. A major contributor to premature death is cardiovascular disease (CVD). We investigated associations of (genetic liability for) depressive disorder, bipolar disorder and schizophrenia with a range of CVD traits and examined to what degree these were driven by important confounders.

We included participants of the Dutch Lifelines cohort (N = 147 337) with information on self-reported lifetime diagnosis of depressive disorder, bipolar disorder, or schizophrenia and CVD traits. Employing linear mixed-effects models, we examined associations between mental illness diagnoses and CVD, correcting for psychotropic medication, demographic and lifestyle factors. In a subsample (N = 73 965), we repeated these analyses using polygenic scores (PGSs) for the three mental illnesses.

There was strong evidence that depressive disorder diagnosis is associated with increased arrhythmia and atherosclerosis risk and lower heart rate variability, even after confounder adjustment. Positive associations were also found for the depression PGSs with arrhythmia and atherosclerosis. Bipolar disorder was associated with a higher risk of nearly all CVD traits, though most diminished after adjustment. The bipolar disorder PGSs did not show any associations. While the schizophrenia PGSs was associated with increased arrhythmia risk and lower heart rate variability, schizophrenia diagnosis was not. All mental illness diagnoses were associated with lower blood pressure and a lower risk of hypertension.

Our study shows widespread associations of (genetic liability to) mental illness (primarily depressive disorder) with CVD, even after confounder adjustment. Future research should focus on clarifying potential causal pathways between mental illness and CVD.

Magnetic resonance imaging (MRI) studies on major depressive disorder (MDD) have predominantly found short-term electroconvulsive therapy (ECT)-related gray matter volume (GMV) increases, but research on the long-term stability of such changes is missing. Our aim was to investigate long-term GMV changes over a 2-year period after ECT administration and their associations with clinical outcome.

In this nonrandomized longitudinal study, patients with MDD undergoing ECT (n = 17) are assessed three times by structural MRI: Before ECT (t0), after ECT (t1) and 2 years later (t2). A healthy (n = 21) and MDD non-ECT (n = 33) control group are also measured three times within an equivalent time interval. A 3(group) × 3(time) ANOVA on whole-brain level and correlation analyses with clinical outcome variables is performed.

Analyses yield a significant group × time interaction (pFWE < 0.001) resulting from significant volume increases from t0 to t1 and decreases from t1 to t2 in the ECT group, e.g., in limbic areas. There are no effects of time in both control groups. Volume increases from t0 to t1 correlate with immediate and delayed symptom increase, while volume decreases from t1 to t2 correlate with long-term depressive outcome (all p ⩽ 0.049).

Volume increases induced by ECT appear to be a transient phenomenon as volume strongly decreased 2 years after ECT. Short-term volume increases are associated with less symptom improvement suggesting that the antidepressant effect of ECT is not due to volume changes. Larger volume decreases are associated with poorer long-term outcome highlighting the interplay between disease progression and structural changes.

This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long–term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression.

An observational cohort using data from ANTLER (N = 478), a double-blind placebo-controlled trial. The primary outcome was time to relapse using the retrospective CIS-R. Participants were followed for 12 months.

Primary outcome was available for 468 participants. Time to relapse in those with more than five previous episodes of depression was shorter, hazard ratio (HR) 1.84 (95% confidence interval [CI] 1.23–2.75) compared to people with two episodes; HR 1.57 (95% CI 1.01–2.43) after adjustment. The residual symptoms of depression at baseline were also associated with increased relapse: HR 1.05 (95% CI 1.01–1.09) and HR 1.06 (95% CI 1.01–1.12) in the adjusted model. There was evidence of reduced rate of relapse in older age of onset group: HR 0.86 (95% CI 0.78–0.95); HR attenuated after adjustment HR 0.91 (95% CI 0.81–1.02). There was no evidence of an association between duration of the current episode and residual anxiety symptoms with relapse.

The number of previous episodes and residual symptoms of depression were associated with increased likelihood of relapse. These factors could inform joint decision making when patients are considering tapering off maintenance antidepressant treatment or considering other treatments to prevent relapse.

Early-life stressful experiences are associated with increased risk of adverse psychological outcomes in later life. However, much less is known about associations between early-life positive experiences, such as participation in cognitively stimulating activities, and late-life mental health. We investigated whether greater engagement in cognitively stimulating activities in early life is associated with lower risk of depression and anxiety in late life.

We surveyed former participants of the St. Louis Baby Tooth study, between 22 June 2021 and 25 March 2022 to collect information on participants' current depression/anxiety symptoms and their early-life activities (N = 2187 responded). A composite activity score was created to represent the early-life activity level by averaging the frequency of self-reported participation in common cognitively stimulating activities in participants' early life (age 6, 12, 18), each rated on a 1 (least frequent) to 5 (most frequent) point scale. Depression/anxiety symptoms were measured by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Screener (GAD-7). We used logistic regressions to estimate odds ratios (OR) and 95% confidence intervals (CI) of outcome risk associated with frequency of early-life activity.

Each one-point increase in the early-life composite cognitive activity score was associated with an OR of 0.54 (95% CI 0.38–0.77) for late-life depression and an OR of 0.94 (95% CI 0.61–1.43) for late-life anxiety, adjusting for age, sex, race, parental education, childhood family structure, and socioeconomic status.

More frequent participation in cognitively stimulating activities during early life was associated with reduced risk of late-life depression.

Suicidal behaviors are prevalent among college students; however, students remain reluctant to seek support. We developed a predictive algorithm to identify students at risk of suicidal behavior and used telehealth to reduce subsequent risk.

Data come from several waves of a prospective cohort study (2016–2022) of college students (n = 5454). All first-year students were invited to participate as volunteers. (Response rates range: 16.00–19.93%). A stepped-care approach was implemented: (i) all students received a comprehensive list of services; (ii) those reporting past 12-month suicidal ideation were directed to a safety planning application; (iii) those identified as high risk of suicidal behavior by the algorithm or reporting 12-month suicide attempt were contacted via telephone within 24-h of survey completion. Intervention focused on support/safety-planning, and referral to services for this high-risk group.

5454 students ranging in age from 17–36 (s.d. = 5.346) participated; 65% female. The algorithm identified 77% of students reporting subsequent suicidal behavior in the top 15% of predicted probabilities (Sensitivity = 26.26 [95% CI 17.93–36.07]; Specificity = 97.46 [95% CI 96.21–98.38], PPV = 53.06 [95% CI 40.16–65.56]; AUC range: 0.895 [95% CIs 0.872–0.917] to 0.966 [95% CIs 0.939–0.994]). High-risk students in the Intervention Cohort showed a 41.7% reduction in probability of suicidal behavior at 12-month follow-up compared to high-risk students in the Control Cohort.

Predictive risk algorithms embedded into universal screening, coupled with telehealth intervention, offer significant potential as a suicide prevention approach for students.

Childhood trauma has been linked to increased risk of schizophrenia and social dysfunction, and oxytocin and its receptor gene have been implicated in regulating social behavior. This study investigated the potential role of oxytocin and oxytocin receptor gene (OXTR) in mediating the effects of childhood trauma on social functioning in schizophrenia.

The study consisted of 382 patients with schizophrenia and 178 healthy controls who were assessed using the Taiwanese version of the Childhood Trauma Questionnaire (CTQ-SF), the Social Functioning Scale (SFS), and plasma oxytocin levels. DNA was extracted to genotype the OXTR and ten single-nucleotide polymorphisms (SNPs; rs2254298, rs237885, rs237887, rs237899, rs53576, rs9840864, rs13316193, rs7632287, rs1042778, and rs237895) were selected.

Patients with schizophrenia showed higher CTQ-SF scores (t = 12.549, p < 0.001), lower SFS scores (t = −46.951, p < 0.001), and lower plasma oxytocin levels (t = −5.448, p < 0.001) compared to healthy controls. The study also found significant differences in OXTR SNPs between both groups, with risk alleles being more prevalent in patients with schizophrenia (t = 2.734, p = 0.006). Results indicated a significant moderated mediation effect, with oxytocin and the OXTR SNPs partially mediating the relationship between childhood trauma exposure and social functioning in patients with schizophrenia (index of mediation = 0.038, 95% CI [0.033–0.044]).

The findings suggest that oxytocin and its receptor gene may be promising targets for interventions aimed at improving social functioning in patients with a history of childhood trauma and schizophrenia. However, further research is needed to fully understand these effects and the potential of oxytocin-based interventions in this population.

Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown.

Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. CBD) and linear between-group relationships, such that placebo > CBD > controls or controls > CBD > placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses.

Placebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo.

These findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.

We investigated disparities in the clinical management of self-harm following hospital presentation with self-harm according to level of socio-economic deprivation (SED) in England.

108 092 presentations to hospitals (by 57 306 individuals) after self-harm in the Multicenter Study of Self-harm spanning 17 years. Area-level SED was based on the English Index of Multiple Deprivation. Information about indicators of clinical care was obtained from each hospital's self-harm monitoring systems. We assessed the associations of SED with indicators of care using mixed effect models.

Controlling for confounders, psychosocial assessment and admission to a general medical ward were less likely for presentations by patients living in more deprived areas relative to presentations by patients from the least deprived areas. Referral for outpatient mental health care was less likely for presentations by patients from the two most deprived localities (most deprived: adjusted odd ratio [aOR] 0.77, 95% CI 0.71–0.83, p < 0.0001; 2nd most deprived: aOR 0.80, 95% CI 0.74–0.87, p < 0.0001). Referral to substance use services and ‘other’ services increased with increased SED. Overall, referral for aftercare was less likely following presentations by patients living in the two most deprived areas (most deprived: aOR 0.85, 95% CI 0.78–0.92, p < 0.0001; 2nd most deprived: aOR 0.86, 95% CI 0.79–0.94, p = 0.001).

SED is associated with differential care for patients who self-harm in England. Inequalities in care may exacerbate the risk of adverse outcomes in this disadvantaged population. Further work is needed to understand the reasons for these differences and ways of providing more equitable care.

Two established staging models outline the longitudinal progression in bipolar disorder (BD) based on episode recurrence or inter-episodic functioning. However, underlying neurobiological mechanisms and corresponding biomarkers remain unexplored. This study aimed to investigate if global and (sub)cortical brain structures, along with brain-predicted age difference (brain-PAD) reflect illness progression as conceptualized in these staging models, potentially identifying brain-PAD as a biomarker for BD staging.

In total, 199 subjects with bipolar-I-disorder and 226 control subjects from the Dutch Bipolar Cohort with a high-quality T1-weighted magnetic resonance imaging scan were analyzed. Global and (sub)cortical brain measures and brain-PAD (the difference between biological and chronological age) were estimated. Associations between individual brain measures and the stages of both staging models were explored.

A higher brain-PAD (higher biological age than chronological age) correlated with an increased likelihood of being in a higher stage of the inter-episodic functioning model, but not in the model based on number of mood episodes. However, after correcting for the confounding factors lithium-use and comorbid anxiety, the association lost significance. Global and (sub)cortical brain measures showed no significant association with the stages.

These results suggest that brain-PAD may be associated with illness progression as defined by impaired inter-episodic functioning. Nevertheless, the significance of this association changed after considering lithium-use and comorbid anxiety disorders. Further research is required to disentangle the intricate relationship between brain-PAD, illness stages, and lithium intake or anxiety disorders. This study provides a foundation for potentially using brain-PAD as a biomarker for illness progression.

To test for publication bias with alprazolam, the most widely prescribed benzodiazepine, by comparing its efficacy for panic disorder using trial results from (1) the published literature and (2) the US Food and Drug Administration (FDA).

From FDA reviews, we included data from all phase 2/3 efficacy trials of alprazolam extended-release (Xanax XR) for the treatment of panic disorder. A search for matching publications was performed using PubMed and Google Scholar. Publication bias was examined by comparing: (1) overall trial results (positive or not) according to the FDA v. corresponding publications; (2) effect size (Hedges's g) based on FDA data v. published data.

The FDA review showed that five trials were conducted, only one of which (20%) was positive. Of the four not-positive trials, two were published conveying a positive outcome; the other two were not published. Thus, according to the published literature, three trials were conducted and all (100%) were positive. Alprazolam's effect size calculated using FDA data was 0.33 (CI95% 0.07–0.60) v. 0.47 (CI95% 0.30–0.65) using published data, an increase of 0.14, or 42%.

Publication bias substantially inflates the apparent efficacy of alprazolam XR.

Social cognition impairments are a common feature of alcohol use disorders (AUD). However, it remains unclear whether these impairments are solely the consequence of chronic alcohol consumption or whether they could be a marker of vulnerability.

The present study implemented a family history approach to address this question for a key process of social cognition: theory of mind (ToM). Thirty healthy adults with a family history of AUD (FH+) and 30 healthy adults with a negative family history of AUD (FH−), matched for age, sex, and education level, underwent an fMRI cartoon-vignette paradigm assessing cognitive and affective ToM. Participants also completed questionnaires evaluating anxiety, depressive symptoms, childhood trauma, and alexithymia.

Results indicated that FH+ individuals differed from FH− individuals on affective but not cognitive ToM processing, at both the behavioral and neural levels. At the behavioral level, the FH+ group had lower response accuracy for affective ToM compared with the FH− group. At the neural level, the FH+ group had higher brain activations in the left insula and inferior frontal cortex during affective ToM processing. These activations remained significant when controlling for depressive symptoms, anxiety, and childhood trauma.

These findings highlight difficulties during affective ToM processing among first-degree relatives of AUD patients, supporting the idea that some of the impairments exhibited by these patients may already be present before the onset of AUD and may be considered a marker of vulnerability.

Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms.

In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006–2010, age = 55.0 ± 7.5 [40–70] years; second visit: 2014–2019; age = 62.7 ± 7.5 [44–80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and depressive symptoms on the second visit among 138 multimodal imaging phenotypes.

Longitudinal data were consistent with significant bidirectional causal relationship between SLEs and depressive symptoms. In cross-sectional analyses, SLEs were significantly associated with lower bilateral nucleus accumbal volume and lower fractional anisotropy of the forceps major. Depressive symptoms were significantly associated with extensive white matter hyperintensities, thinner cortex, lower subcortical volume, and white matter microstructural deficits, mainly in corticostriatal-limbic structures. Lower bilateral nucleus accumbal volume were the only imaging phenotypes with overlapping effects of depressive symptoms and SLEs (B = −0.032 to −0.023, p = 0.006–0.034). Depressive symptoms and SLEs significantly partially mediated the effects of each other on left and right nucleus accumbens volume (proportion of effects mediated = 12.7–14.3%, p < 0.001−p = 0.008). For the left nucleus accumbens, post-hoc seed-based analysis showed lower resting-state functional connectivity with the left orbitofrontal cortex (cluster size = 83 voxels, p = 5.4 × 10−5) in participants with high v. no SLEs.

The nucleus accumbens may play a key role in the reciprocity between stress and depressive symptoms.