Life stress and blunted reward processing each have been associated with the onset and maintenance of major depressive disorder. However, much of this work has been cross-sectional, conducted in separate lines of inquiry, and focused on recent life stressor exposure, despite the fact that theories of depression posit that stressors can have cumulative effects over the lifespan. To address these limitations, we investigated whether acute and chronic stressors occurring over the lifespan interacted with blunted reward processing to predict increases in depression over time in healthy youth.

Participants were 245 adolescent girls aged 8–14 years old (Mage = 12.4, s.d. = 1.8) who were evaluated at baseline and two years later. The reward positivity (RewP), an event-related potential measure of reward responsiveness, was assessed at baseline using the doors task. Cumulative lifetime exposure to acute and chronic stressors was assessed two years later using the Stress and Adversity Inventory for Adolescents (Adolescent STRAIN). Finally, depressive symptoms were assessed at both baseline and follow-up using the Children's Depression Inventory.

As hypothesized, greater lifetime acute stressor exposure predicted increases in depressive symptoms over two years, but only for youth exhibiting a blunted RewP. This interaction, however, was not found for chronic stressors.

Lifetime acute stressor exposure may be particularly depressogenic for youth exhibiting a blunted RewP. Conversely, a robust RewP may be protective in the presence of greater acute lifetime stressor exposure.

Major depressive disorder (MDD) is often accompanied by changes in appetite and weight. Prior task-based functional magnetic resonance imaging (fMRI) findings suggest these MDD phenotypes are associated with altered reward and interoceptive processing.

Using resting-state fMRI data, we compared the fractional amplitude of low-frequency fluctuations (fALFF) and seed-based connectivity (SBC) among hyperphagic (n = 77), hypophagic (n = 66), and euphagic (n = 42) MDD groups and a healthy comparison group (n = 38). We examined fALFF and SBC in a mask restricted to reward [nucleus accumbens (NAcc), putamen, caudate, ventral pallidum, and orbitofrontal cortex (OFC)] and interoceptive (anterior insula and hypothalamus) regions and also performed exploratory whole-brain analyses. SBC analyses included as seeds the NAcc and also regions demonstrating group differences in fALFF (i.e. right lateral OFC and right anterior insula). All analyses used threshold-free cluster enhancement.

Mask-restricted analyses revealed stronger fALFF in the right lateral OFC, and weaker fALFF in the right anterior insula, for hyperphagic MDD v. healthy comparison. We also found weaker SBC between the right lateral OFC and left anterior insula for hyperphagic MDD v. healthy comparison. Whole-brain analyses revealed weaker fALFF in the right anterior insula, and stronger SBC between the right lateral OFC and left precentral gyrus, for hyperphagic MDD v. healthy comparison. Findings were no longer significant after controlling for body mass index, which was higher for hyperphagic MDD.

Our results suggest hyperphagic MDD may be associated with altered activity in and connectivity between interoceptive and reward regions.

Causes of childhood behavior problems remain poorly understood. Enriched family environments and corresponding brain development may reduce the risk of their onset, but research investigating white matter neurodevelopmental pathways explaining associations between the family environment and behavior remains limited. We hypothesized that more positive prenatal and mid-childhood family functioning – a measure of a family's problem solving and supportive capacity – would be associated with two markers of preadolescent white matter neurodevelopment related to reduced behavior problems: higher global fractional anisotropy (FA) and lower global mean diffusivity (MD).

Data are from 2727 families in the Generation R Study, the Netherlands. Mothers reported family functioning (McMaster Family Assessment Device, range 1–4, higher scores indicate healthier functioning) prenatally and in mid-childhood (mean age 6.1 years). In preadolescence (mean age 10.1), the study collected diffusion-weighted scans. We computed standardized global MD and FA values by averaging metrics from 27 white matter tracts, and we fit linear models adjusting for possible confounders to examine global and tract-specific outcomes.

Prenatal and mid-childhood family functioning scores were moderately correlated, r = 0.38. However, only prenatal family functioning – and not mid-childhood functioning – was associated with higher global FA and lower global MD in preadolescence in fully adjusted models: βglobal FA = 0.11 (95% CI 0.00, 0.21) and βglobal MD = −0.15 (95% CI −0.28, −0.03) per one-unit increase in functioning score. Sensitivity and tract-specific analyses supported these global findings.

These results suggest high-functioning prenatal or perinatal family environments may confer lasting white matter neurodevelopmental benefits into preadolescence.

The purpose of this paper is to identify the trajectory of conduct and emotional problems for young people within the general population at four time points (between 9 years 7 months and 16 years 6 months), investigate their relationship with hyperactive/inattentive traits and explore the moderating effect of autistic social traits (ASTs).

Data from 9305 individuals involved in The Avon Longitudinal Study of Parents and Children (ALSPAC) study were included. Conduct and emotional problems and hyperactive/inattentive traits were measured by the Strengths and Difficulties Questionnaire. ASTs were assessed using the Social Communication Disorder Checklist. Individual trajectories for conduct and emotional problems were identified via growth curve modelling. Hyperactive/inattentive traits were included within the growth curve model as a time-varying covariate to determine their effect on these outcomes. Finally, participants were split into two groups (below and above clinical threshold ASTs Groups) and multi-group invariance testing was conducted on the data to identify the moderating effect of ASTs on the relationship between hyperactive/inattentive traits and outcomes (i.e. conduct and emotional problems).

Hyperactive/inattentive traits were associated with higher rates of conduct and emotional problems for both boys and girls. The presence of ASTs moderated these relationships for boys, but not for girls, by increasing the risk of boys with hyperactive/inattentive traits developing greater conduct and emotional problems.

These findings underscore the importance of identifying hyperactive/inattentive traits and ASTs in young people and addressing the increased risk of conduct and emotional problems. Research and clinical implications are explored.

Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics in individuals at clinical high-risk for psychosis (CHR-P) is associated with a higher risk of an imminent transition to psychosis. Despite their tolerability profile and potential beneficial effects, baseline exposure to antidepressants (AD) in CHR-P has surprisingly received far less attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap.

Systematic scrutiny of Medline and Cochrane library, performed up to 1 August 2021, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on AD baseline exposure in relation to such outcome.

Of 1942 identified records, 16 studies were included in the systematic review and meta-analysis. 26% of the participants were already exposed to AD at baseline; at the end of the follow-up 13.5% (95% CI 10.2–17.1%) of them (n = 448) transitioned to psychosis against 21.0% (18.9 to 23.3%) of non-AD exposed CHR-P (n = 1371). CHR-P participants who were already under AD treatment at baseline had a lower risk of transition than non-AD exposed CHR-P. The RR was 0.71 (95% CI 0.56–0.90) in the fixed-effects model (z = −2.79; p = 0.005), and 0.78 (0.58–1.05) in the random-effects model (z = −1.77; p = 0.096; tau-squared = 0.059). There was no relevant heterogeneity (Cochran's Q = 18.45; df = 15; p = 0.239; I2 = 18.7%).

Ongoing AD exposure at inception in CHR-P is associated to a reduced risk of transition to psychosis at follow up.

Cognitive processing therapy (CPT) and prolonged exposure (PE) delivered in an individual setting are efficacious and effective treatments for veterans with posttraumatic stress disorder (PTSD). Group CPT has been shown to be less efficacious than individual CPT, however, evidence regarding real-world effectiveness is limited.

We conducted a retrospective, observational, comparative effectiveness study including veterans that received at least eight sessions of group CPT, individual CPT, or individual PE, and were discharged from PTSD residential treatment at the Department of Veterans Affairs between 1 October 2015, and 30 September 2020. PTSD symptom severity was assessed with the PTSD Checklist for DSM-5 (PCL-5) and treatments delivered in a group (CPT) or individual (CPT or PE) setting were compared at discharge and 4-month post-discharge follow-up.

Of 6735 veterans, 3888 [653 women (17%), median (IQR) age 45 (35–55) years] received individual and 2847 [206 women (7.2%), median (IQR) age 42 (34–54)] received group therapy. At discharge, improvement in PTSD severity was statistically greater among those treated individually (mean difference on the PCL-5, 2.55 (95% CI 1.61–3.49); p = <0.001]. However, the difference was smaller than the minimal clinically important difference of 7.9 points. The groups did not differ significantly at 4-month follow-up [mean difference on the PCL-5, 0.37 (95% CI −0.86 to 1.60); p = 0.551].

Group CPT was associated with a slightly smaller reduction of PTSD symptom severity than individual CPT or PE in veterans at the end of residential treatment. There were no differences at 4-month follow-up.

Negative self-views, especially in the domain of power (i.e. social-rank), characterize social anxiety (SA). Neuroimaging studies on self-evaluations in SA have mainly focused on subcortical threat processing systems. Yet, self-evaluation may concurrently invoke diverse affective processing, as motivational systems related to desired self-views may also be activated. To investigate the conflictual nature that may accompany self-evaluation of certain social domains in SA, we examined brain activity related to both threat and reward processing.

Participants (N = 74) differing in self-reported SA-severity underwent fMRI while completing a self-evaluation task, wherein they judged the self-descriptiveness of high- v. low-intensity traits in the domains of power and affiliation (i.e. social connectedness). Participants also completed two auxiliary fMRI tasks designated to evoke reward- and threat-related activations in the ventral striatum (VS) and amygdala, respectively. We hypothesized that self-evaluations in SA, particularly in the domain of power, involve aberrant brain activity related to both threat and reward processing.

SA-severity was more negatively associated with power than with affiliation self-evaluations. During self-evaluative judgment of high-power (e.g. dominant), SA-severity associated with increased activity in the VS and ventromedial prefrontal cortex. Moreover, SA-severity correlated with higher similarity between brain activity patterns activated by high-power traits and patterns activated by incentive salience (i.e. reward anticipation) in the VS during the reward task.

Our findings indicate that self-evaluation of high-power in SA involves excessive striatal reward-related activation, and pinpoint the downregulation of VS-VMPFC activity within such self-evaluative context as a potential neural outcome for therapeutic interventions.

Empirically validated digital interventions for recurrent binge eating typically target numerous hypothesized change mechanisms via the delivery of different modules, skills, and techniques. Emerging evidence suggests that interventions designed to target and isolate one key change mechanism may also produce meaningful change in core symptoms. Although both ‘broad’ and ‘focused’ digital programs have demonstrated efficacy, no study has performed a direct, head-to-head comparison of the two approaches. We addressed this through a randomized non-inferiority trial.

Participants with recurrent binge eating were randomly assigned to a broad (n = 199) or focused digital intervention (n = 199), or a waitlist (n = 202). The broad program targeted dietary restraint, mood intolerance, and body image disturbances, while the focused program exclusively targeted dietary restraint. Primary outcomes were eating disorder psychopathology and binge eating frequency.

In intention-to-treat analyses, both intervention groups reported greater improvements in primary and secondary outcomes than the waitlist, which were sustained at an 8-week follow-up. The focused intervention was not inferior to the broad intervention on all but one outcome, but was associated with higher rates of attrition and non-compliance.

Focused digital interventions that are designed to target one key change mechanism may produce comparable symptom improvements to broader digital interventions, but appear to be associated with lower engagement.

Patients with bipolar disorder (BD) show reduced fractional anisotropy (FA) compared to patients with major depressive disorder (MDD). Little is known about whether these differences are mood state-independent or influenced by acute symptom severity. Therefore, the aim of this study was (1) to replicate abnormalities in white matter microstructure in BD v. MDD and (2) to investigate whether these vary across depressed, euthymic, and manic mood.

In this cross-sectional diffusion tensor imaging study, n = 136 patients with BD were compared to age- and sex-matched MDD patients and healthy controls (HC) (n = 136 each). Differences in FA were investigated using tract-based spatial statistics. Using interaction models, the influence of acute symptom severity and mood state on the differences between patient groups were tested.

Analyses revealed a main effect of diagnosis on FA across all three groups (ptfce-FWE = 0.003). BD patients showed reduced FA compared to both MDD (ptfce-FWE = 0.005) and HC (ptfce-FWE < 0.001) in large bilateral clusters. These consisted of several white matter tracts previously described in the literature, including commissural, association, and projection tracts. There were no significant interaction effects between diagnosis and symptom severity or mood state (all ptfce-FWE > 0.704).

Results indicated that the difference between BD and MDD was independent of depressive and manic symptom severity and mood state. Disruptions in white matter microstructure in BD might be a trait effect of the disorder. The potential of FA values to be used as a biomarker to differentiate BD from MDD should be further addressed in future studies using longitudinal designs.

Young people are most vulnerable to suicidal behaviours but least likely to seek help. A more elaborate study of the intrinsic and extrinsic correlates of suicidal ideation and behaviours particularly amid ongoing population-level stressors and the identification of less stigmatising markers in representative youth populations is essential.

Participants (n = 2540, aged 15–25) were consecutively recruited from an ongoing large-scale household-based epidemiological youth mental health study in Hong Kong between September 2019 and 2021. Lifetime and 12-month prevalence of suicidal ideation, plan, and attempt were assessed, alongside suicide-related rumination, hopelessness and neuroticism, personal and population-level stressors, family functioning, cognitive ability, lifetime non-suicidal self-harm, 12-month major depressive disorder (MDD), and alcohol use.

The 12-month prevalence of suicidal ideation, ideation-only (no plan or attempt), plan, and attempt was 20.0, 15.4, 4.6, and 1.3%, respectively. Importantly, multivariable logistic regression findings revealed that suicide-related rumination was the only factor associated with all four suicidal outcomes (all p < 0.01). Among those with suicidal ideation (two-stage approach), intrinsic factors, including suicide-related rumination, poorer cognitive ability, and 12-month MDE, were specifically associated with suicide plan, while extrinsic factors, including coronavirus disease 2019 (COVID-19) stressors, poorer family functioning, and personal life stressors, as well as non-suicidal self-harm, were specifically associated with suicide attempt.

Suicide-related rumination, population-level COVID-19 stressors, and poorer family functioning may be important less-stigmatising markers for youth suicidal risks. The respective roles played by not only intrinsic but also extrinsic factors in suicide plan and attempt using a two-stage approach should be considered in future preventative intervention work.

Cognitive Bias Modification for paranoia (CBM-pa) is a novel, theory-driven psychological intervention targeting the biased interpretation of emotional ambiguity associated with paranoia. Study objectives were (i) test the intervention's feasibility, (ii) provide effect size estimates, (iii) assess dose–response and (iv) select primary outcomes for future trials.

In a double-blind randomised controlled trial, sixty-three outpatients with clinically significant paranoia were randomised to either CBM-pa or an active control (text reading) between April 2016 and September 2017. Patients received one 40 min session per week for 6 weeks. Assessments were given at baseline, after each interim session, post-treatment, and at 1- and 3-months post-treatment.

A total of 122 patients were screened and 63 were randomised. The recruitment rate was 51.2%, with few dropouts (four out of 63) and follow-up rates were 90.5% (1-month) and 93.7% (3-months). Each session took 30–40 min to complete. There was no statistical evidence of harmful effects of the intervention. Preliminary data were consistent with efficacy of CBM-pa over text-reading control: patients randomised to the intervention, compared to control patients, reported reduced interpretation bias (d = −0.48 to −0.76), improved symptoms of paranoia (d = −0.19 to −0.38), and lower depressed and anxious mood (d = −0.03 to −0.29). The intervention effect was evident after the third session.

CBM-pa is feasible for patients with paranoia. A fully powered randomised control trial is warranted.

Research has shown a strong relationship between hallucinations and suicidal behaviour in general population samples. Whether hallucinations also index suicidal behaviour risk in groups at elevated risk of suicidal behaviour, namely in individuals with a sexual assault history, remains to be seen.

We assessed whether hallucinations were markers of risk for suicidal behaviour among individuals with a sexual assault history.

Using the cross-sectional 2007 (N = 7403) and 2014 (N = 7546) Adult Psychiatric Morbidity Surveys, we assessed for an interaction between sexual assault and hallucinations in terms of the odds of suicide attempt, as well as directly comparing the prevalence of suicide attempt in individuals with a sexual assault history with v. without hallucinations.

Individuals with a sexual assault history had increased odds of hallucinations and suicide attempt compared to individuals without a sexual assault history in both samples. There was a significant interaction between sexual assault and hallucinations in terms of the odds of suicide attempt. In total, 14–19% of individuals with a sexual assault history who did not report hallucinations had one or more suicide attempt. This increased to 33–52% of individuals with a sexual assault history who did report hallucinations (2007, aOR = 2.85, 1.71–4.75; 2014, aOR = 4.52, 2.78–7.35).

Hallucinations are a risk marker for suicide attempt even among individuals with an elevated risk of suicidal behaviour, specifically individuals with a sexual assault history. This finding highlights the clinical significance of hallucinations with regard to suicidal behaviour risk, even among high-risk populations.

Clinical intervention in early stages of psychotic disorders is crucial for the prevention of severe symptomatology trajectories and poor outcomes. Genetic variability is studied as a promising modulator of prognosis, thus novel approaches considering the polygenic nature of these complex phenotypes are required to unravel the mechanisms underlying the early progression of the disorder.

The sample comprised of 233 first-episode psychosis (FEP) subjects with clinical and cognitive data assessed periodically for a 2-year period and 150 matched controls. Polygenic risk scores (PRSs) for schizophrenia, bipolar disorder, depression, education attainment and cognitive performance were used to assess the genetic risk of FEP and to characterize their association with premorbid, baseline and progression of clinical and cognitive status.

Schizophrenia, bipolar disorder and cognitive performance PRSs were associated with an increased risk of FEP [false discovery rate (FDR) ⩽ 0.027]. In FEP patients, increased cognitive PRSs were found for FEP patients with more cognitive reserve (FDR ⩽ 0.037). PRSs reflecting a genetic liability for improved cognition were associated with a better course of symptoms, functionality and working memory (FDR ⩽ 0.039). Moreover, the PRS of depression was associated with a worse trajectory of the executive function and the general cognitive status (FDR ⩽ 0.001).

Our study provides novel evidence of the polygenic bases of psychosis and its clinical manifestation in its first stage. The consistent effect of cognitive PRSs on the early clinical progression suggests that the mechanisms underlying the psychotic episode and its severity could be partially independent.

Cognitive-behavioural therapy (CBT) has been shown to be an effective treatment for depression and anxiety. However, most research has focused on the sum scores of symptoms. Relatively little is known about how individual symptoms respond.

Longitudinal models were used to explore how depression and generalised anxiety symptoms behave over the course of CBT in a retrospective, observational cohort of patients from primary care settings (n = 5306). Logistic mixed models were used to examine the probability of being symptom-free across CBT appointments, using the 9-item Patient Health Questionnaire and the 7-item Generalised Anxiety Disorder scale as measures.

All symptoms improve across CBT treatment. The results suggest that low mood/hopelessness and guilt/worthlessness improved quickest relative to other depressive symptoms, with sleeping problems, appetite changes, and psychomotor retardation/agitation improving relatively slower. Uncontrollable worry and too much worry were the anxiety symptoms that improved fastest; irritability and restlessness improved the slowest.

This research suggests there is a benefit to examining symptoms rather than sum scores alone. Investigations of symptoms provide the potential for precision psychiatry and may explain some of the heterogeneity observed in clinical outcomes when only sum scores are considered.

To advance knowledge regarding the etiology of eating disorders, we characterized the sequencing of eating disorder symptom emergence for adolescent girls who subsequently developed anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD) for community-recruited adolescents and tested whether prodromal symptoms increased risk for future onset of each eating disorder.

Data collected from adolescent girls (N = 496; M age = 13.02, s.d. = 0.73) who completed a diagnostic interview annually over an 8-year period were used to address these aims.

For all four eating disorders, compensatory weight-control behaviors were the first behavioral symptom to emerge and weight/shape overvaluation was the first cognitive symptom to emerge. Moreover, lower-than-expected BMI predicted future AN onset, binge eating and all cognitive symptoms predicted future BN onset, weight/shape overvaluation predicted future BED onset, and compensatory behavior and all cognitive symptoms predicted future PD onset. These predictive effects were small-to-large in magnitude. Collectively, prodromal symptoms predicted an eating disorder onset with 83–87% accuracy.

Results suggest that compensatory weight-control behaviors and weight/shape overvaluation typically emerge before other prodromal symptoms in all eating disorders during adolescence. Moreover, different prodromal symptoms seem to predict future onset of different eating disorders. Screening adolescent girls for these prodromal symptoms and implementing indicated prevention programs designed to reduce these symptoms may prove effective in preventing future onset of eating disorders.

In a recent eye-tracking study we found a differential dwell time pattern for negatively-valenced and neutral faces among patients with posttraumatic stress disorder (PTSD), trauma-exposed healthy control (TEHCs), and healthy control (HC) participants. Here, we explored whether these group differences relate to resting-state functional connectivity (rsFC) patterns of brain areas previously linked to both attention processes and PTSD. These encompass the amygdala, dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), and nucleus accumbens (NAcc).

Ten minutes magnetic resonance imaging rsFC scans were recorded in 17 PTSD patients, 21 TEHCs, and 16 HCs. Participants then completed a free-viewing eye-tracking task assessing attention allocation outside the scanner. Dwell time on negatively-valenced stimuli (DT%) were assessed relative to functional connectivity in the aforementioned seed regions of interest (amygdala, dACC, dlPFC, vlPFC, and NAcc) to whole-brain voxel-wise rsFC.

As previously reported, group differences occurred in attention allocation to negative-valence stimuli, with longer dwell time on negatively valence stimuli in the PTSD and TEHC groups than the HC group. Higher DT% correlated with weaker NAcc-orbitofrontal cortex (OFC) connectivity in patients with PTSD. Conversely, a positive association emerged in the HC group between DT% and NAcc-OFC connectivity.

While exploratory in nature, present findings may suggest that reward-related brain areas are involved in disengaging attention from negative-valenced stimuli, and possibly in regulating ensuing negative emotions.

We provide an umbrella review of the reported polysomnographic changes in patients with neuropsychiatric diseases compared with healthy controls.

An electronic literature search was conducted in EMBASE, MEDLINE, All EBM databases, CINAHL, and PsycINFO. Meta-analyses of case–control studies investigating the polysomnographic changes in patients with neuropsychiatric diseases were included. For each meta-analysis, we estimated the summary effect size using random effects models, the 95% confidence interval, and the 95% prediction interval. We also estimated between-study heterogeneity, evidence of excess significance bias, and evidence of small-study effects. The levels of evidence of polysomnographic changes in neuropsychiatric diseases were ranked as follows: not significant, weak, suggestive, highly suggestive, or convincing.

We identified 27 articles, including 465 case–control studies in 27 neuropsychiatric diseases. The levels of evidence of polysomnographic changes in neuropsychiatric diseases were highly suggestive for increased sleep latency and decreased sleep efficiency (SE) in major depressive disorder (MDD), increased N1 percentage, and decreased N2 percentage, SL and REML in narcolepsy, and decreased rapid eye movement (REM) sleep percentage in Parkinson's disease (PD). The suggestive evidence decreased REM latency in MDD, decreased total sleep time and SE in PD, and decreased SE in posttraumatic stress disorder and in narcolepsy.

The credibility of evidence for sleep characteristics in 27 neuropsychiatric diseases varied across polysomnographic variables and diseases. When considering the patterns of altered PSG variables, no two diseases had the same pattern of alterations, suggesting that specific sleep profiles might be important dimensions for defining distinct neuropsychiatric disorders.

Value-based decision-making impairment in depression is a complex phenomenon: while some studies did find evidence of blunted reward learning and reward-related signals in the brain, others indicate no effect. Here we test whether such reward sensitivity deficits are dependent on the overall value of the decision problem.

We used a two-armed bandit task with two different contexts: one ‘rich’, one ‘poor’ where both options were associated with an overall positive, negative expected value, respectively. We tested patients (N = 30) undergoing a major depressive episode and age, gender and socio-economically matched controls (N = 26). Learning performance followed by a transfer phase, without feedback, were analyzed to distangle between a decision or a value-update process mechanism. Finally, we used computational model simulation and fitting to link behavioral patterns to learning biases.

Control subjects showed similar learning performance in the ‘rich’ and the ‘poor’ contexts, while patients displayed reduced learning in the ‘poor’ context. Analysis of the transfer phase showed that the context-dependent impairment in patients generalized, suggesting that the effect of depression has to be traced to the outcome encoding. Computational model-based results showed that patients displayed a higher learning rate for negative compared to positive outcomes (the opposite was true in controls).

Our results illustrate that reinforcement learning performances in depression depend on the value of the context. We show that depressive patients have a specific trouble in contexts with an overall negative state value, which in our task is consistent with a negativity bias at the learning rates level.

While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need.

Forty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments. Maps of extracellular free-water (FW) and fractional anisotropy of cellular tissue (FAT) were compared between individuals with psychosis and HCs using tract-based spatial statistics and FSL's Randomise. FAT and FW values were extracted, averaged across all voxels that demonstrated group differences, and then utilized to test for the influence of age, medication, age of onset, duration of illness, symptom severity, and intelligence.

Individuals with adolescent-onset psychosis exhibited pronounced FW and FAT abnormalities compared to HCs. FAT reductions were spatially more widespread in ADO-SCZ. FW increases, however, were only present in psychotic ADO-BPD. In HCs, but not in individuals with adolescent-onset psychosis, FAT was positively related to age.

We observe evidence for cellular (FAT) and extracellular (FW) white matter abnormalities in adolescent-onset psychosis. Although cellular white matter abnormalities were more prominent in ADO-SCZ, such alterations may reflect a shared trait, i.e. neurodevelopmental pathology, present across the psychosis spectrum. Extracellular abnormalities were evident in psychotic ADO-BPD, potentially indicating a more dynamic, state-dependent brain reaction to psychosis.

Childhood maltreatment (CM) represents a potent risk factor for major depressive disorder (MDD), including poorer treatment response. Altered resting-state connectivity in the fronto-limbic system has been reported in maltreated individuals. However, previous results in smaller samples differ largely regarding localization and direction of effects.

We included healthy and depressed samples [n = 624 participants with MDD; n = 701 healthy control (HC) participants] that underwent resting-state functional MRI measurements and provided retrospective self-reports of maltreatment using the Childhood Trauma Questionnaire. A-priori defined regions of interest [ROI; amygdala, hippocampus, anterior cingulate cortex (ACC)] were used to calculate seed-to-voxel connectivities.

No significant associations between maltreatment and resting-state connectivity of any ROI were found across MDD and HC participants and no interaction effect with diagnosis became significant. Investigating MDD patients only yielded maltreatment-associated increased connectivity between the amygdala and dorsolateral frontal areas [pFDR < 0.001; η2partial = 0.050; 95%-CI (0.023–0.085)]. This effect was robust across various sensitivity analyses and was associated with concurrent and previous symptom severity. Particularly strong amygdala-frontal associations with maltreatment were observed in acutely depressed individuals [n = 264; pFDR < 0.001; η2partial = 0.091; 95%-CI (0.038–0.166)). Weaker evidence – not surviving correction for multiple ROI analyses – was found for altered supracallosal ACC connectivity in HC individuals associated with maltreatment.

The majority of previous resting-state connectivity correlates of CM could not be replicated in this large-scale study. The strongest evidence was found for clinically relevant maltreatment associations with altered adult amygdala-dorsolateral frontal connectivity in depression. Future studies should explore the relevance of this pathway for a maltreated subgroup of MDD patients.