The UK Biobank is a large middle-aged cohort recruited in 2006–2010. We used data from its participants to analyze mortality, survival, and causes of death associated with mental disorders.

Our exposures were mental disorders identified using (1) symptom-based outcomes derived from an online Mental Health Questionnaire (n = 157 329), including lifetime/current depression, lifetime/current generalized anxiety disorder, lifetime/recent psychotic experience, lifetime bipolar disorder, current alcohol use disorder, and current posttraumatic stress disorder and (2) hospital data linkage of diagnoses within the International Classification of Diseases, 10th revision (ICD-10) (n = 502 422), including (A) selected diagnoses or groups of diagnoses corresponding to symptom-based outcomes and (B) all psychiatric diagnoses, grouped by ICD-10 section. For all exposures, we estimated age-adjusted mortality rates and hazard ratios, as well as proportions of deaths by cause.

We found significantly increased mortality risk associated with all mental disorders identified by symptom-based outcomes, except for lifetime generalized anxiety disorder (with hazard ratios in the range of 1.08–3.0). We also found significantly increased mortality risk associated with all conditions identified by hospital data linkage, including selected ICD-10 diagnoses or groups of diagnoses (2.15–7.87) and ICD-10 diagnoses grouped by section (2.02–5.44). Causes of death associated with mental disorders were heterogeneous and mostly natural.

In a middle-aged cohort, we found a higher mortality risk associated with most mental disorders identified by symptom-based outcomes and with all disorders or groups of disorders identified by hospital data linkage of ICD-10 diagnoses. The majority of deaths associated with mental disorders were natural.

Prevention programs that are ‘transdiagnostic’ may be more cost-effective and beneficial, in terms of reducing levels of psychopathology in the general population, than those focused on a specific disorder. This randomized controlled study evaluated the efficacy of one such intervention program called Resilience Training (RT).

College students who reported mildly elevated depressive or subclinical psychotic symptoms (‘psychotic experiences' (PEs)) (n = 107) were randomized to receiving RT (n = 54) or to a waitlist control condition (n = 53). RT consists of a four-session intervention focused on improving resilience through the acquisition of mindfulness, self-compassion, and mentalization skills. Measures of symptoms and these resilience-enhancing skills were collected before and after the 4-week RT/waitlist period, with a follow-up assessment 12-months later.

Compared to the waitlist control group, RT participants reported significantly greater reductions in PEs, distress associated with PEs, depression, and anxiety, as well as significantly greater improvements in resilience, mindfulness, self-compassion, and positive affect, following the 4-week RT/waitlist period (all p < 0.03). Moreover, improvements in resilience-promoting skills were significantly correlated with symptom reductions (all p < 0.05). Lastly, the RT-related reductions in PEs and associated distress were maintained at the 12-month follow-up assessment.

RT is a brief, group-based intervention associated with improved resilience and reduced symptoms of psychopathology, with sustained effects on PEs, in transdiagnostically at-risk young adults. Follow-up studies can further assess the efficacy of RT relative to other interventions and test whether it can reduce the likelihood of developing a serious mental illness.

Grey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, but patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls (HC). The relative excess of GM may indicate putative compensatory responses, though to date its relevance is unclear.

343 first-episode treatment-naïve patients with schizophrenia (FES) and 342 HC were recruited. Multivariate source-based morphometry was performed to identify covarying ‘networks' of grey matter concentration (GMC). Neurocognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and symptom burden using the Positive and Negative Symptoms Scale (PANSS) were obtained. Bivariate linear relationships between GMC and cognition/symptoms were studied.

Compared to healthy subjects, FES had prominently lower GMC in two components; the first consists of the anterior insula, inferior frontal gyrus, anterior cingulate and the second component with the superior temporal gyrus, precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Higher GMC was seen in adjacent areas of the middle and superior temporal gyrus, middle frontal gyrus, inferior parietal cortex and putamen. Greater GMC of this component was associated with lower duration of untreated psychosis, less severe positive symptoms and better performance on cognitive tests.

In untreated stages of schizophrenia, both a distributed lower and higher GMC is observable. While the higher GMC is relatively modest, it occurs across frontoparietal, temporal and subcortical regions in association with reduced illness burden suggesting a compensatory role for higher GMC in the early stages of schizophrenia.

Chronic muscle diseases (MD) are progressive and cause wasting and weakness in muscles and are associated with reduced quality of life (QoL). The ACTMuS trial examined whether Acceptance and Commitment Therapy (ACT) as an adjunct to usual care improved QoL for such patients as compared to usual care alone.

This two-arm, randomised, multicentre, parallel design recruited 155 patients with MD (Hospital and Depression Scale ⩾ 8 for depression or ⩾ 8 for anxiety and Montreal Cognitive Assessment ⩾ 21/30). Participants were randomised, using random block sizes, to one of two groups: standard medical care (SMC) (n = 78) or to ACT in addition to SMC (n = 77), and were followed up to 9 weeks. The primary outcome was QoL, assessed by the Individualised Neuromuscular Quality of Life Questionnaire (INQoL), the average of five subscales, at 9-weeks. Trial registration was NCT02810028.

138 people (89.0%) were followed up at 9-weeks. At all three time points, the adjusted group difference favoured the intervention group and was significant with moderate to large effect sizes. Secondary outcomes (mood, functional impairment, aspects of psychological flexibility) also showed significant differences between groups at week 9.

ACT in addition to usual care was effective in improving QoL and other psychological and social outcomes in patients with MD. A 6 month follow up will determine the extent to which gains are maintained.

Network modeling has been applied in a range of trauma-exposed samples, yet results are limited by an over reliance on cross-sectional data. The current analyses used posttraumatic stress disorder (PTSD) symptom data collected over a 5-year period to estimate a more robust between-subject network and an associated symptom change network.

A PTSD symptom network is measured in a sample of military veterans across four time points (Ns = 1254, 1231, 1106, 925). The repeated measures permit isolating between-subject associations by limiting the effects of within-subject variability. The result is a highly reliable PTSD symptom network. A symptom slope network depicting covariation of symptom change over time is also estimated.

Negative trauma-related emotions had particularly strong associations with the network. Trauma-related amnesia, sleep disturbance, and self-destructive behavior had weaker overall associations with other PTSD symptoms.

PTSD's network structure appears stable over time. There is no single ‘most important’ node or node cluster. The relevance of self-destructive behavior, sleep disturbance, and trauma-related amnesia to the PTSD construct may deserve additional consideration.

Borderline personality disorder (BPD) is associated with altered activity in the prefrontal cortex (PFC) and amygdala, yet no studies have examined fronto-limbic circuitry in borderline adolescents and emerging adults. Here, we examined the contribution of fronto-limbic effective connectivity (EC) to the longitudinal stability of emotion-related impulsivity, a key feature of BPD, in symptomatic adolescents and young adults.

We compared resting-state EC in 82 adolescents and emerging adults with and without clinically significant borderline symptoms (n BPD = 40, ages 13–30). Group-specific directed networks were estimated amongst fronto-limbic nodes including PFC, ventral striatum (VS), central amygdala (CeN), and basolateral amygdala (BLA). We examined the association of directed centrality metrics with initial levels and rates of change in emotion-related impulsivity symptoms over a one-year follow-up using latent growth curve models (LGCMs).

In controls, ventromedial prefrontal cortex (vmPFC) and dorsal ACC had a directed influence on CeN and VS, respectively. In the BPD group, bilateral BLA had a directed influence on CeN, whereas in the healthy group CeN influenced BLA. LGCMs indicated that emotion-related impulsivity was stable across a one-year follow-up in the BPD group. Further, higher EC of R CeN to other regions in controls was associated with stronger within-person decreases in emotion-related impulsivity.

Functional inputs from BLA and vmPFC appear to play competing roles in influencing CeN activity. In borderline adolescents and young adults, BLA may predominate over CeN activity, while in controls the ability of CeN to influence BLA activity predicted more rapid reductions in emotion-related impulsivity.

Depressive symptoms, such as depressed mood, are common in older adults and associated with an increased risk for morbidity and mortality. Given the evidence that sleep disturbance and alterations in interferon (IFN)-γ biology are associated with depression risk, this study examines the separate and joint contributions of poor sleep maintenance and IFN-γ to depressed mood in older adults.

Community-dwelling, non-depressed older adults (n = 36, 72.1 ± 6.8 years) underwent a night of polysomnography to assess sleep maintenance [i.e. wake time after sleep onset (WASO)]. The morning after polysomnography, plasma levels of IFN-γ were evaluated along with self-reported depressed mood throughout the day. Multivariate linear regression tested associations of WASO and IFN-γ with the severity of depressed mood. In addition, moderation and mediation models examined the role of IFN-γ for the relationship between WASO and depressed mood.

A greater amount of WASO (p < 0.05) and higher levels of IFN-γ (p < 0.01) were both associated with the severity of depressed mood. Moreover, IFN-γ moderated the relationship between WASO and depressed mood (p < 0.01), such that WASO was more strongly related to the depressed mood among those with higher IFN-γ, than among those with lower IFN-γ. However, IFN-γ did not mediate the relationship between WASO and depressed mood.

In this study of older adults, poor sleep maintenance and higher levels of IFN-γ were both related to depressed mood. Moreover, IFN-γ moderated the relationship between poor sleep maintenance and depressed mood. Together, these findings suggest that older adults with higher IFN-γ are at heightened risk for depressive symptoms following sleep disturbance.

The association between executive dysfunction, brain dysconnectivity, and inflammation is a prominent feature across major psychiatric disorders (MPDs), schizophrenia, bipolar disorder, and major depressive disorder. A dimensional approach is warranted to delineate their mechanistic interplay across MPDs.

This single site study included a total of 1543 participants (1058 patients and 485 controls). In total, 1169 participants underwent diffusion tensor and resting-state functional magnetic resonance imaging (745 patients and 379 controls completed the Wisconsin Card Sorting Test). Fractional anisotropy (FA) and regional homogeneity (ReHo) assessed structural and functional connectivity, respectively. Pro-inflammatory cytokine levels [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] were obtained in 325 participants using blood samples collected with 24 h of scanning. Group differences were determined for main measures, and correlation and mediation analyses and machine learning prediction modeling were performed.

Executive deficits were associated with decreased FA, increased ReHo, and elevated IL-1β and IL-6 levels across MPDs, compared to controls. FA and ReHo alterations in fronto-limbic-striatal regions contributed to executive deficits. IL-1β mediated the association between FA and cognition, and IL-6 mediated the relationship between ReHo and cognition. Executive cognition was better predicted by both brain connectivity and cytokine measures than either one alone for FA-IL-1β and ReHo-IL-6.

Transdiagnostic associations among brain connectivity, inflammation, and executive cognition exist across MPDs, implicating common neurobiological substrates and mechanisms for executive deficits in MPDs. Further, inflammation-related brain dysconnectivity within fronto-limbic-striatal regions may represent a transdiagnostic dimension underlying executive dysfunction that could be leveraged to advance treatment.

Psychosocial deficits, such as emotional, behavioral and social problems, reflect the most common and disabling consequences of pediatric traumatic brain injury (TBI). Their causes and recovery likely differ from physical and cognitive skills, due to disruption to developing brain networks and the influence of the child's environment. Despite increasing recognition of post-injury behavioral and social problems, there exists a paucity of research regarding the incidence of social impairment, and factors predicting risk and resilience in the social domain over time since injury.

Using a prospective, longitudinal design, and a bio-psychosocial framework, we studied children with TBI (n = 107) at baseline (pre-injury function), 6 months, 1 and 2-years post-injury. We assessed intellectual ability, attention/executive function, social cognition, social communication and socio-emotional function. Children underwent structural magnetic resonance imaging (MRI) at 2–8 weeks post-injury. Parents rated their child's socio-emotional function and their own mental health, family function and perceived burden.

We distinguished five social recovery profiles, characterized by a complex interplay between environment and pre- and post-TBI factors, with injury factors playing a lesser role. Resilience in social competence was linked to intact family and parent function, intact pre-injury adaptive abilities, post-TBI cognition and social participation. Vulnerability in the social domain was related to poor pre- and post-injury adaptive abilities, greater behavioral concerns, and poorer pre- and post-injury parent health and family function.

We identified five distinct social recovery trajectories post-child-TBI, each characterized by a unique biopsychosocial profile, highlighting the importance of comprehensive social assessment and understanding of factors contributing to social impairment, to target resources and interventions to children at highest risk.

The sense of ‘loss of control’ (LOC), or a feeling of being unable to stop eating or control what or how much one is eating, is the most salient aspect of binge eating. However, the neural alterations that may contribute to this experience and eating behavior remain poorly understood.

We used functional near-infrared spectroscopy (fNIRS) to measure activation in the prefrontal cortices of 23 women with bulimia nervosa (BN) and 23 healthy controls (HC) during two tasks: a novel go/no-go task requiring inhibition of eating responses, and a standard go/no-go task requiring inhibition of button-pressing responses.

Women with BN made more commission errors on both tasks. BN subgroups with the most severe LOC eating (n = 12) and those who felt most strongly that they binge ate during the task (n = 12) showed abnormally reduced bilateral ventromedial prefrontal cortex (vmPFC) and right ventrolateral prefrontal cortex (vlPFC) activation associated with eating-response inhibition. In the entire BN sample, lower eating-task activation in right vlPFC was related to more frequent and severe LOC eating, but no group differences in activation were detected on either task when this full sample was compared with HC. BN severity was unrelated to standard-task activation.

Results provide initial evidence that diminished PFC activation may directly contribute to more severe eating-specific control deficits in BN. Our findings support vmPFC and vlPFC dysfunction as promising treatment targets, and indicate that eating-specific tasks and fNIRS may be useful tools for identifying neural mechanisms underlying dysregulated eating.

Fewer than half of patients with major depressive disorder (MDD) respond to psychotherapy. Pre-emptively informing patients of their likelihood of responding could be useful as part of a patient-centered treatment decision-support plan.

This prospective observational study examined a national sample of 807 patients beginning psychotherapy for MDD at the Veterans Health Administration. Patients completed a self-report survey at baseline and 3-months follow-up (data collected 2018–2020). We developed a machine learning (ML) model to predict psychotherapy response at 3 months using baseline survey, administrative, and geospatial variables in a 70% training sample. Model performance was then evaluated in the 30% test sample.

32.0% of patients responded to treatment after 3 months. The best ML model had an AUC (SE) of 0.652 (0.038) in the test sample. Among the one-third of patients ranked by the model as most likely to respond, 50.0% in the test sample responded to psychotherapy. In comparison, among the remaining two-thirds of patients, <25% responded to psychotherapy. The model selected 43 predictors, of which nearly all were self-report variables.

Patients with MDD could pre-emptively be informed of their likelihood of responding to psychotherapy using a prediction tool based on self-report data. This tool could meaningfully help patients and providers in shared decision-making, although parallel information about the likelihood of responding to alternative treatments would be needed to inform decision-making across multiple treatments.

Many individuals with posttraumatic stress disorder (PTSD) have limited access to first-line treatments, warranting the development of remotely-delivered treatments. Attention bias modification (ABM), targeting perturbed threat-related attentional patterns, shows promise when delivered in-person. However, previous studies found ABM to be ineffective when delivered remotely. Randomized clinical trials usually applied two variations of ABM: ABM away from threat or attention control training (ACT) balancing attention between threat-related and neutral stimuli. We tested remotely-delivered ACT/ABM with tighter supervision and video-based interactions that resemble in-clinic protocols. We expected to replicate the results of in-clinic trials, in which ACT outperformed ABM for PTSD.

In this double-blinded, parallel-group randomized controlled trial, 60 patients diagnosed with PTSD were randomized (ABM n = 30; ACT n = 30). Patients performed eight bi-weekly remotely-delivered supervised ABM/ACT sessions. Symptoms were assessed pre- and post-treatment with Clinician-Administered PTSD Scale 5 (CAPS-5) severity score and PTSD diagnosis as the primary outcomes. Current depressive episode, current anxiety-related comorbidity, and time elapsed since the trauma were examined as potential moderators of treatment outcome.

Significant decrease in CAPS-5 severity scores and PTSD diagnosis was observed following both ACT and ABM with no between-group difference. Patients without depression or whose trauma occurred more recently had greater symptom reduction in the ACT than the ABM group.

Contrary to our expectation, symptoms decreased similarly following ACT and ABM. Moderator analyses suggest advantage for ACT in non-depressed patients and patients whose trauma occurred more recently. Further refinements in remotely-delivered ABM/ACT may be needed.

Subthreshold depression could be a significant precursor to and a risk factor for major depression. However, reliable estimates of the prevalence and its contribution to developing major depression under different terminologies depicting subthreshold depression have to be established.

By searching PubMed and Web of Science using predefined inclusion criteria, we included 1 129 969 individuals from 113 studies conducted. The prevalence estimates were calculated using the random effect model. The incidence risk ratio (IRR) was estimated by measuring the ratio of individuals with subthreshold depression who developed major depression compared to that of non-depressed individuals from 19 studies (88, 882 individuals).

No significant difference in the prevalence among the different terminologies depicting subthreshold depression (Q = 1.96, p = 0.5801) was found. By pooling the prevalence estimates of subthreshold depression in 113 studies, we obtained a summary prevalence of 11.02% [95% confidence interval (CI) 9.78–12.33%]. The youth group had the highest prevalence (14.17%, 95% CI 8.82–20.55%), followed by the elderly group (12.95%, 95% CI 11.41-14.58%) and the adult group (8.92%, 95% CI 7.51–10.45%). Further analysis of 19 studies' incidence rates showed individuals with subthreshold depression had an increased risk of developing major depression (IRR = 2.95, 95% CI 2.33–3.73), and the term minor depression showed the highest IRR compared with other terms (IRR = 3.97, 95% CI 3.17–4.96).

Depression could be a spectrum disorder, with subthreshold depression being a significant precursor to and a risk factor for major depression. Proactive management of subthreshold depression could be effective for managing the increasing prevalence of major depression.

People with severe mental illness (SMI) have an elevated risk of obesity but the causes and mechanisms are unclear. We explored the familial association between parental SMI and body mass index (BMI) in middle-aged offspring. Our objective was to determine if the offspring of either parent with SMI have an increased risk for obesity.

The Northern Finland Birth Cohort 1966 is a cohort study of offspring with expected date of birth in 1966. The data include originally 12 068 mothers and 12 231 children from the provinces of Lapland and Oulu in Finland. The final study sample included 5050 middle-aged offspring. Parental SMI was used as exposure in the study. BMI measured at the age of 46 years was used as a primary outcome.

Risk for obesity was elevated in the offspring of mothers with SMI [overweight: adjusted odds ratio (OR) 1.93 (1.29–2.90), obese class I: 1.97 (1.20–3.25), obese classes II–III: 2.98 (1.67–5.33)]. For the offspring of either parent with SMI, statistically significant results were found in obese class I and obese classes II–III [overweight: adjusted OR 1.21 (0.94–1.54), obese class I: 1.52 (1.03–1.08), obese classes II–III: 1.53 (1.01–2.32)].

We found an elevated risk of obesity in the middle-aged offspring of either parent with SMI, especially in the offspring of mothers with SMI. Thus, there might be a common familial pathway leading to the co-occurrence of obesity and SMI.

Sex differences in brain structure and neurodevelopment occur in non-clinical populations. We investigated whether sex had a similar effect on developmental domains amongst boys and girls with a familial risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP), and controls.

Through Danish registries, we identified 522 7-year-old children (242 girls) with FHR-SZ, FHR-BP, and controls. We assessed their performance within the domains of neurocognition, motor function, language, social cognition, social behavior, psychopathology, and home environment.

FHR-SZ boys compared with FHR-SZ girls had a higher proportion of disruptive behavior and attention-deficit hyperactivity disorder (ADHD) and exhibited lower performance in manual dexterity, balance, and emotion recognition. No sex differences were found between boys and girls within FHR-BP group. Compared with controls, both FHR-SZ boys and FHR-SZ girls showed impaired processing speed and working memory, had lower levels of global functioning, and were more likely to live in an inadequate home environment. Compared with control boys, FHR-SZ boys showed impaired manual dexterity, social behavior, and social responsiveness, and had a higher proportion of ADHD and disruptive behavior disorder diagnoses. Stress and adjustment disorders were more common in FHR-BP boys compared with control boys. We found no differences between FHR-BP girls and control girls.

Impairment within neurodevelopmental domains associated within FHR-SZ boys v. FHR-SZ girls was most evident among boys, whereas no sex differences were found within the FHR-BP group (FHR-BP boys v. FHR-BP girls). FHR-SZ boys exhibited the highest proportion of early developmental impairments.

While comorbidity of clinical high-risk for psychosis (CHR-P) status and social anxiety is well-established, it remains unclear how social anxiety and positive symptoms covary over time in this population. The present study aimed to determine whether there are more than one covariant trajectory of social anxiety and positive symptoms in the North American Prodrome Longitudinal Study cohort (NAPLS 2) and, if so, to test whether the different trajectory subgroups differ in terms of genetic and environmental risk factors for psychotic disorders and general functional outcome.

In total, 764 CHR individuals were evaluated at baseline for social anxiety and psychosis risk symptom severity and followed up every 6 months for 2 years. Application of group-based multi-trajectory modeling discerned three subgroups based on the covariant trajectories of social anxiety and positive symptoms over 2 years.

One of the subgroups showed sustained social anxiety over time despite moderate recovery in positive symptoms, while the other two showed recovery of social anxiety below clinically significant thresholds, along with modest to moderate recovery in positive symptom severity. The trajectory group with sustained social anxiety had poorer long-term global functional outcomes than the other trajectory groups. In addition, compared with the other two trajectory groups, membership in the group with sustained social anxiety was predicted by higher levels of polygenic risk for schizophrenia and environmental stress exposures.

Together, these analyses indicate differential relevance of sustained v. remitting social anxiety symptoms in the CHR-P population, which in turn may carry implications for differential intervention strategies.

Adolescent antisocial behavior (AB) is a public health concern due to the high financial and social costs of AB on victims and perpetrators. Neural systems involved in reward and loss processing are thought to contribute to AB. However, investigations into these processes are limited: few have considered anticipatory and consummatory components of reward, response to loss, nor whether associations with AB may vary by level of callous-unemotional (CU) traits.

A population-based community sample of 128 predominantly low-income youth (mean age = 15.9 years; 42% male) completed a monetary incentive delay task during fMRI. A multi-informant, multi-method latent variable approach was used to test associations between AB and neural response to reward and loss anticipation and outcome and whether CU traits moderated these associations.

AB was not associated with neural response to reward but was associated with reduced frontoparietal activity during loss outcomes. This association was moderated by CU traits such that individuals with higher levels of AB and CU traits had the largest reductions in frontoparietal activity. Co-occurring AB and CU traits were also associated with increased precuneus response during loss anticipation.

Findings indicate that AB is associated with reduced activity in brain regions involved in cognitive control, attention, and behavior modification during negative outcomes. Moreover, these reductions are most pronounced in youth with co-occurring CU traits. These findings have implications for understanding why adolescents involved in AB continue these behaviors despite severe negative consequences (e.g. incarceration).

Acceptability is an important factor for predicting intervention use and potential treatment outcomes in psychosocial interventions. Cognitive remediation (CR) improves cognition and functioning in people with a diagnosis of schizophrenia, but its acceptability, and the impact of participants and treatment characteristics, remain to be investigated. Few studies provide a direct measure of acceptability, but treatment drop-out rates are often available and represent a valid surrogate.

The systematic search conducted for the most comprehensive CR outcomes database for schizophrenia was updated in December 2020. Eligible studies were randomized clinical trials comparing CR with any other control condition in patients diagnosed with schizophrenia spectrum disorders and that also reported drop-out in treatment and control arms separately. Acceptability was measured as odd-ratios (OR) of drop-out.

Of 2119 identified reports, 151 studies, reporting 169 comparisons between CR and control interventions with 10 477 participants were included in the analyses. The overall rate of drop-out was 16.58% for CR programs and 15.21% for control conditions. In the meta-analysis, no difference emerged between CR interventions and controls [OR 1.10, 95% confidence interval (CI) 0.96–1.25, p = 0.177]. Factors improving acceptability were: inpatient only recruitment, participants with fewer years of education and lower premorbid IQ, the presence of all CR core elements, and the presence of techniques to transfer cognitive gains into real-world functioning.

CR for people diagnosed with schizophrenia is effective and has a good acceptability profile, similar to that of other evidence-based psychosocial interventions.

Neuroimaging studies on major depressive disorder (MDD) have identified an extensive range of brain structural abnormalities, but the exact neural mechanisms associated with MDD remain elusive. Most previous studies were performed with voxel- or surface-based morphometry which were univariate methods without considering spatial information across voxels/vertices.

Brain morphology was investigated using voxel-based morphometry (VBM) and source-based morphometry (SBM) in 1082 MDD patients and 990 healthy controls (HCs) from the REST-meta-MDD Consortium. We first examined group differences in regional grey matter (GM) volumes and structural covariance networks between patients and HCs. We then compared first-episode, drug-naïve (FEDN) patients, and recurrent patients. Additionally, we assessed the effects of symptom severity and illness duration on brain alterations.

VBM showed decreased GM volume in various regions in MDD patients including the superior temporal cortex, anterior and middle cingulate cortex, inferior frontal cortex, and precuneus. SBM returned differences only in the prefrontal network. Comparisons between FEDN and recurrent MDD patients showed no significant differences by VBM, but SBM showed greater decreases in prefrontal, basal ganglia, visual, and cerebellar networks in the recurrent group. Moreover, depression severity was associated with volumes in the inferior frontal gyrus and precuneus, as well as the prefrontal network.

Simultaneous application of VBM and SBM methods revealed brain alterations in MDD patients and specified differences between recurrent and FEDN patients, which tentatively provide an effective multivariate method to identify potential neurobiological markers for depression.

The mental health impact of the initial years of military service is an under-researched area. This study is the first to explore mental health trajectories and associated predictors in military members across the first 3–4 years of their career to provide evidence to inform early interventions.

This prospective cohort study surveyed Australian Defence personnel (n = 5329) at four time-points across their early military career. Core outcomes were psychological distress (K10+) and posttraumatic stress symptoms [four-item PTSD Checklist (PCL-4)] with intra-individual, organizational and event-related trajectory predictors. Latent class growth analyses (LCGAs) identified subgroups within the sample that followed similar longitudinal trajectories for these outcomes, while conditional LCGAs examined the variables that influenced patterns of mental health.

Three clear trajectories emerged for psychological distress: resilient (84.0%), worsening (9.6%) and recovery (6.5%). Four trajectories emerged for post-traumatic stress, including resilient (82.5%), recovery (9.6%), worsening (5.8%) and chronic subthreshold (2.3%) trajectories. Across both outcomes, prior trauma exposure alongside modifiable factors, such as maladaptive coping styles, and increased anger and sleep difficulties were associated with the worsening and chronic subthreshold trajectories, whilst members in the resilient trajectories were more likely to be male, report increased social support from family/friends and Australian Defence Force (ADF) sources, and use adaptive coping styles.

The emergence of symptoms of mental health problems occurs early in the military lifecycle for a significant proportion of individuals. Modifiable factors associated with wellbeing identified in this study are ideal targets for intervention, and should be embedded and consolidated throughout the military career.