Methamphetamine (METH) dependence is a globally significant public health concern with no efficacious treatment. Trait impulsivity is associated with the initiation, maintenance, and recurrence of substance abuse. However, the presence of these associations in METH addiction, as well as the underlying neurobiological mechanisms, remains incompletely understood.

We scanned 110 individuals with METH use disorder (MUDs) and 55 matched healthy controls (HCs) using T1-weighted imaging and assessed their drug use characteristics and trait impulsivity. Surface-based morphometry and graph theoretical analysis were used to investigate group differences in brain morphometry and network attributes. Partial correlations were conducted to investigate the relationships between brain morphometric changes, drug use parameters, and trait impulsivity. Mediation analyses examined how trait impulsivity and drug craving influenced the link between brain morphometric change and MUD severity in patients.

MUDs exhibited thinner thickness in the left fusiform gyrus and right pars opercularis, as well as diminished small-world properties in their structural covariance networks (SCNs) compared to HCs. Furthermore, reduced cortical thickness in the right pars opercularis was linked to motor impulsivity (MI) and MUD severity, and the association between the right pars opercularis thickness and MUD severity was significantly mediated by both MI and cue-induced craving.

These findings suggest that MUDs exhibit distinct brain structural abnormalities in both the cortical thickness and SCNs and highlight the critical role of impulse control in METH addiction. This insight may offer a potential neurobiological target for developing therapeutic interventions to treat addiction and prevent relapse.

Lesbian, gay, and bisexual (LGB) individuals are more than twice as likely to experience anxiety and depression compared with heterosexuals. Minority stress theory posits that stigma and discrimination contribute to chronic stress, potentially affecting clinical treatment. We compared psychological therapy outcomes between LGB and heterosexual patients by gender.

Retrospective cohort data were obtained from seven NHS talking therapy services in London, from April 2013 to December 2023. Of 100,389 patients, 94,239 reported sexual orientation, 7,422 identifying as LGB. The primary outcome was reliable recovery from anxiety and depression. Secondary outcomes were reliable improvement, depression and anxiety severity, therapy attrition, and engagement. Analyses were stratified by gender and employed multilevel regression models, adjusting for sociodemographic and clinical covariates.

After adjustment, gay men had higher odds of reliable recovery (OR: 1.23, 95% CI: 1.13–1.34) and reliable improvement (OR: 1.16, 95% CI: 1.06–1.28) than heterosexual men, with lower attrition (OR: 0.88, 95% CI: 0.80–0.97) and greater reductions in depression (MD: 0.51, 95% CI: 0.28–0.74) and anxiety (MD: 0.45, 95% CI: 0.25–0.65). Bisexual men (OR: 0.67, 95% CI: 0.54–0.83) and bisexual women (OR: 0.84, 95% CI: 0.77–0.93) had lower attrition than heterosexuals. Lesbian and bisexual women, and bisexual men, attended slightly more sessions (MD: 0.02–0.03, 95% CI: 0.01–0.04) than heterosexual patients. No other differences were observed.

Despite significant mental health burdens and stressors, LGB individuals had similar, if not marginally better, outcomes and engagement with psychological therapy compared with heterosexual patients.

Anhedonia, a transdiagnostic feature common to both Major Depressive Disorder (MDD) and Schizophrenia (SCZ), is characterized by abnormalities in hedonic experience. Previous studies have used machine learning (ML) algorithms without focusing on disorder-specific characteristics to independently classify SCZ and MDD. This study aimed to classify MDD and SCZ using ML models that integrate components of hedonic processing.

We recruited 99 patients with MDD, 100 patients with SCZ, and 113 healthy controls (HC) from four sites. The patient groups were allocated to distinct training and testing datasets. All participants completed a modified Monetary Incentive Delay (MID) task, which yielded features categorized into five hedonic components, two reward consequences, and three reward magnitudes. We employed a stacking ensemble model with SHapley Additive exPlanations (SHAP) values to identify key features distinguishing MDD, SCZ, and HC across binary and multi-class classifications.

The stacking model demonstrated high classification accuracy, with Area Under the Curve (AUC) values of 96.08% (MDD versus HC) and 91.77% (SCZ versus HC) in the main dataset. However, the MDD versus SCZ classification had an AUC of 57.75%. The motivation reward component, loss reward consequence, and high reward magnitude were the most influential features within respective categories for distinguishing both MDD and SCZ from HC (p < 0.001). A refined model using only the top eight features maintained robust performance, achieving AUCs of 96.06% (MDD versus HC) and 95.18% (SCZ versus HC).

The stacking model effectively classified SCZ and MDD from HC, contributing to understanding transdiagnostic mechanisms of anhedonia.

Providing psychotherapy at 50 sessions in a year (starting twice weekly) led to faster and greater improvements in depression and personality functioning compared to 25 sessions, starting weekly for patients with depression and personality disorder (PD). This study reports long-term dosage effects at 18 and 24 months.

In a pragmatic, double-randomized clinical trial, 246 outpatients with depression and PD were assigned to (1) 25 or 50 sessions and (2) Short-term Psychodynamic Supportive Psychotherapy (SPSP) or Schema Therapy (ST). Depression severity was assessed with the Beck Depression Inventory-II. Secondary outcomes included diagnostic remission of depression (MINI-plus), PD (SCID-II/SCID-5-P), and treatment-specific measures. Intention-to-treat analyses were conducted.

At 18 and 24 months, BDI-II means did not differ between dosage groups (19.0 for 25 sessions versus 19.1 for 50 sessions; d = −0.01; 95% CI = −0.35-0.37, p = 0.96). The lower-dosage group improved during follow-up (−2.6 BDI points, p = 0.031), which may be partly attributed to additional therapy received by a subgroup. Remission rates at 24 months were 66% for depression and 76% for PD, with no differences between conditions.

Higher psychotherapy dosage led to faster initial improvements, but long-term outcomes were not superior to those achieved with a lower dosage. These results should be interpreted with caution, as unregulated treatment during follow-up reduced the power to detect significant dosage effects. Both SPSP and ST provide viable alternatives to treatments focused solely on depression.

Comprehensive cognitive remediation improves cognitive and functional outcomes in people with serious mental illness, but the specific components required for effective programs are uncertain. The most common methods to improve cognition are facilitated computerized cognitive training with coaching and teaching cognitive self-management strategies. We compared these methods by dismantling the Thinking Skills for Work program, a comprehensive, validated cognitive remediation program that incorporates both strategies.

In a randomized controlled trial we assigned 203 unemployed people with serious mental illness in supported employment programs at two mental health agencies to receive either the full Thinking Skills for Work (TSW) program, which included computerized cognitive training (based on Cogpack software), or the program with cognitive self-management (CSM) but no computer training. Outcomes included employment, cognition, and mental health over 2 years. To benchmark outcomes, we also examined competitive work outcomes in a similar prior trial comparing the TSW program with supported employment only.

The TSW and CSM groups improved significantly on all outcomes, but there were no differences between the groups. Competitive work outcomes for both groups resembled those of the TSW program in a prior trial and were better than the supported employment-only group in that study, suggesting that participants in both groups benefited from cognitive remediation.

Providing facilitated computerized cognitive training improved neither employment nor cognitive outcomes beyond teaching cognitive self-management strategies in people receiving supported employment. Computerized cognitive training may not be necessary for cognitive remediation programs to improve cognitive and functional outcomes.

Obstetric complications (OCs) are associated with cognitive and brain abnormalities observed in patients with schizophrenia. Gyrification, a measure of cortical integrity sensitive to events occurring during the prenatal and perinatal periods, is also altered in first-episode psychosis (FEP). We examined the relationship between OCs and gyrification in FEP, as well as whether gyrification mediates the relationship between OCs and cognition.

We examined differences in the Local Gyrification Index (LGI) for the frontal, parietal, temporal, occipital, and cingulate cortices between 139 FEP patients and 125 healthy controls (HCs). Regression analyses explored whether OCs and diagnosis interact to explain LGI variation. Parametric mediation analyses were conducted to assess the effect of LGI on the relationship between OCs and cognition for FEP and HC.

Significant LGI differences were observed between FEP patients and HC in the left parietal and bilateral cingulate and occipital cortices. There was a significant interaction between OCs and diagnosis on the left cingulate cortex (LCC) that was specific to males (p = 0.04) and was driven by gestational rather than intrauterine OCs.

In HCs, OCs had a direct effect on working memory (WM) (p = 0.048) in the mediation analysis, whereas in FEP, we observed no significant effect of OCs on either verbal or WM.

OCs interact with diagnosis to predict LCC gyrification, such that males with FEP exposed to OCs exhibit the lowest LGI. OCs influence WM, and LCC gyrification may mediate this relation only in HC, suggesting a differential neurodevelopmental process in psychosis.

There has been debate about the frequency and severity of antidepressant withdrawal effects.

We set out to appraise and reanalyze an influential systematic review by Henssler and colleagues that concluded that withdrawal effects are not particularly common and rarely severe. We repeated the meta-analysis, including only studies where data were derived from systematic measures of withdrawal symptoms.

Most data in the Henssler review are derived from pharmaceutical industry–sponsored efficacy studies in which withdrawal was a minor consideration. Shortcomings of the review include the use of spontaneously reported adverse events to estimate withdrawal symptoms, potential misclassification of withdrawal symptoms as relapse, inclusion of data from retrospective case-note studies, short duration of prior antidepressant use, short observation periods, the overlooking of differences between placebo and drug withdrawal effects, and the use of questionable proxies for severe withdrawal. There were also discrepancies and uncertainties in some figures used. In our reanalysis, we included only the five studies that used a systematic and relevant method to assess the incidence of any withdrawal symptom. Prior treatment was short-term (12 weeks or less) in all but one of these. The pooled percentage was 55% (95% confidence interval, CI, 31% to 81%; N = 601) without subtracting nocebo effects, with high heterogeneity.

Henssler’s review is based on unreliable data and does not provide an adequate basis for the evaluation of antidepressant withdrawal effects. Further good-quality research on antidepressant withdrawal is required.

Previous research has highlighted abnormalities in the pulvinar region of the brain among individuals diagnosed with obsessive-compulsive disorder (OCD). Nevertheless, given the pulvinar’s complex structure, comprising four distinct subnuclei (PuA, PuI, PuL, and PuM), inconsistencies persist regarding both structural and connectivity alterations within this region.

3D T1-weighted magnetic resonance imaging (MRI) and resting-state functional magnetic resonance imaging (rs-fMRI) were used on a cohort consisting of 41 healthy controls and 51 individuals with OCD in order to compare pulvinar connectivity and gray matter volume. Our aim was to compare both connectivity patterns and gray matter volume (GMV) within the PuA, PuI, PuL, and PuM subnuclei between the two groups. First, we examined resting-state connectivity differences in these subnuclei, followed by an analysis of GMV discrepancies to elucidate the potential neuropathological role of the pulvinar in OCD.

Our findings revealed significant connectivity differences in the left PuL, the right PuA, and the left PuA between OCD patients and healthy controls (p < 0.05). Furthermore, the left PuA exhibited both connectivity differences and increased GMV in the OCD group after applying multiple comparison corrections (p = 0.002).

Our study identified functional connectivity alterations within specific subnuclei, including the left and right PuA, and the left PuL, alongside GMV changes in the left PuA. These observations suggest that these distinct regions of the pulvinar may contribute to the pathophysiology of OCD through differences in both functional connectivity and GMV compared to healthy controls.

Limited longitudinal research examining developmental changes in visuospatial working memory (WM) among children and adolescents with autism spectrum disorder (ASD) has prompted our investigation.

We assessed 123 autistic children and adolescents and 145 typically developing controls (TDC) using the Cambridge Neuropsychological Test Automated Battery at baseline (Time 1 [mean age ± SD]: ASD: 13.04 ± 2.86; TDC: 11.53 ± 2.81) and 2–9 years later (Time 2: ASD: 18.08 ± 3.17; TDC: 16.41 ± 3.09) to measure changes of visuospatial (working) memory over time. The linear mixed model was used to compare the differences between ASD and TDC and estimate the effect of changes over time, age, ASD diagnosis, and interactions of Time×Age×ASD. The overall Age×ASD effect was calculated in the spline regression.

Autistic children and adolescents exhibited significantly poorer performance on all spatial tasks and some visual tasks than their TDC counterparts at Time 1 and Time 2, after adjusting for sex, age, attention deficit/hyperactivity disorder (ADHD), and full-scale intelligence quotient. There was an overall improvement from Time 1 to Time 2 across all tasks with significant Age×Time interactions. Significant Age×ASD interactions were observed in the delayed matching to sample, pattern recognition memory (PRM), spatial span (SSP), and spatial working memory (SWM) tasks with no significant Time×ASD interactions. In the quadratic nonlinear model, Age×ASD interactions were significant in PRM and SSP.

Despite significant improvements during the follow-up period, autistic children and adolescents continue to experience persistent deficits in SWM, with a weaker age-related improvement in visuospatial WM than TDC.

The premorbid phase of treatment-resistant schizophrenia (TRS) may reveal underlying mechanisms and inform early interventions. According to the neurodevelopmental hypothesis, treatment resistance may be linked to pronounced developmental impairments. We examined school grades and attendance trajectories in children who later developed TRS.

This case-control study analyzed school grade point average and attendance among all individuals born after 1990 and started on clozapine in Chile’s public health system as a proxy for TRS. Control groups included children later diagnosed with treatment-responsive schizophrenia, bipolar disorder, and unaffected classmates. Linear mixed models accounted for individual and school-level confounders.

We included 1072 children (9929 observations, 29.3% female) subsequently diagnosed with TRS, 323 (2802 observations, 25.7% female) with schizophrenia, 175 (1784 observations, 53.8% female) bipolar disorder, and 273,260 (533,335 observations, 47% female) unaffected classmates. Children who later developed TRS had worse grades across levels than their classmates (−0.26 SD [−0.2, −0.4]), but not treatment-responsive schizophrenia. All severe mental illness groups showed grade declines in later school levels, with TRS showing steeper linear decline than treatment-responsive schizophrenia (group×age of −0.03; 95%CI −0.04, −0.01) and steeper quadratic decline than bipolar disorder (group×age2 of −0.005; −0.01, −0.001). Attendance declined over time in the two groups developing schizophrenia compared to their classmates. Those developing TRS experienced the sharpest drop (group×age compared to schizophrenia −0.03; −0.05, −0.01 and bipolar disorder −0.027; −0.049, −0.006).

TRS may stem from a more aggressive pathological process or pronounced late-maturation abnormality, rather than an early premorbid impairment, suggesting an intervention target.

Most cognitive studies of bipolar disorder (BD) have examined case–control differences on cognitive tests using measures of central tendency, which do not consider intraindividual variability (IIV); a distinct cognitive construct that reliably indexes meaningful cognitive differences between individuals. In this study, we sought to characterize IIV in BD by examining whether it differs from healthy controls (HCs) and is associated with other cognitive measures, clinical variables, and white matter microstructure.

Two hundred and seventeen adults, including 100 BD outpatients and 117 HCs, completed processing speed, sustained attention, working memory, and executive function tasks. A subsample of 55 BD participants underwent diffusion tensor imaging. IIV was operationalized as the individual standard deviation in reaction time on the Continuous Performance Test-Identical Pairs version.

BD participants had significantly increased IIV compared to age-matched controls. Increased IIV was associated with poorer mean performance scores on processing speed, sustained attention, working memory, and executive function tasks, as well as two whole-brain white matter indices: fractional anisotropy and radial diffusivity.

IIV is increased in BD and appears to correlate with other cognitive variables, as well as white matter measures that index reduced structural integrity and demyelination. Thus, IIV may represent a neurobiologically informative cognitive measure for BD research that is worthy of further investigation.

Postpartum depression is prevalent among Black women and associated with intersecting systemic factors and interpersonal discrimination. However, gaps remain in understanding pregnancy-related changes in discrimination experiences that influence postpartum mental health and could inform preventive interventions. We hypothesized that young Black women would experience increasing levels of discrimination across the transition to parenthood, heightening depression risk relative to non-pregnant peers.

Participants comprised 335 Black primiparous women (ages 17-30 at delivery) and 335 age- and discriminationmatched non-pregnant controls from the Pittsburgh Girls Study. Self-reported discrimination experiences were collected at four timepoints: two years pre-pregnancy, one year pre-pregnancy, pregnancy, and one year postpartum for the childbearing sample, with corresponding data from the non-pregnant sample across the same interval (matched pairwise).

Linear increases in discrimination were observed for the nonpregnant participants (BS = .480, SE = .090, p <.001), while childbearing participants showed no overall changes, though younger age predicted greater increases over time. For childbearing participants, both baseline discrimination (BI = .626, SE = .077, p < .001) and increasing discrimination (BS = 2.55, SE = .939, p < .01) predicted postpartum depressive symptoms, controlling for pre-pregnancy depression. Among non-pregnant participants, only baseline discrimination predicted later depression (BI = .912, SE = .081, p < .001).

Experiencing increasing levels of interpersonal discrimination across the transition to parenthood may heighten postpartum depression risk among young Black women, indicating a need for interventions supporting well-being and promoting resilience before, during and after pregnancy.

Difficulties in executive functions (EFs) and internalizing and externalizing problems are prospectively related. However, it remains unclear whether the bidirectional relations between specific EF components and internalizing and externalizing problems at the within-person level vary across developmental stages in childhood and early adolescence.

This study utilized data from seven waves of the Early Childhood Longitudinal Study, Kindergarten Class of 2010–2011 (ECLS-K: 2011), following a nationally representative sample of 15,055 children (mean age at baseline = 5.63 years, SD = 0.37; age range = 4.02–7.83) from kindergarten through fifth grade. Internalizing and externalizing problems and inhibitory control were assessed using teacher-reported measures, while working memory and cognitive flexibility were evaluated using standardized cognitive tasks. Data were analyzed using a random intercept cross-lagged panel model, adjusting for the complex sampling design.

Working memory negatively predicted internalizing problems from kindergarten to first grade, with no significant link to externalizing problems. Cognitive flexibility showed limited effects, with only spring kindergarten externalizing problems predicting lower cognitive flexibility in first grade. Inhibitory control negatively predicted internalizing problems in early childhood, while internalizing problems positively predicted inhibitory control during the kindergarten-to-first-grade transition. Externalizing problems consistently reduced inhibitory control over time. Notably, inhibitory control negatively predicted externalizing problems until third grade but positively predicted them from third to fourth grade.

The findings suggest that while certain EFs can protect against internalizing and externalizing problems in early childhood, these symptoms may also influence EF development, with these interactions evolving as children transition into adolescence.

Depression is closely associated with abnormalities in brain function. Traditional static functional connectivity analyses offer limited insight into the temporal variability of brain activity. Recent advances in dynamic analyses enable a deeper understanding of how depression relates to temporal fluctuations in brain activity.

This study utilized a large resting-state functional magnetic resonance imaging dataset (N = 696) to examine the association between brain dynamics and depression. Two complementary approaches were employed. Hidden Markov modeling (HMM) was used to identify discrete brain states and quantify their temporal switching patterns; temporal variability was computed within and between large-scale functional networks to capture time-varying fluctuations in functional connectivity.

Depression scores were positively associated with switching rate and negatively associated with maximum fractional occupancy. Furthermore, depression scores were significantly associated with greater temporal variability both within and between networks, with particularly strong effects observed in the default mode network, ventral attention network, and frontoparietal network. Together, these findings suggest that individuals with higher depression scores exhibit more unstable brain dynamics.

Our findings reveal that individuals with higher depression levels exhibit greater instability in brain state transitions and increased temporal variability in functional connectivity across large-scale networks. This instability in brain dynamics may contribute to difficulties in emotion regulation and cognitive control. By capturing whole-brain temporal patterns, this study offers a novel perspective on the neural basis of depression.

Major depressive disorder (MDD) is a disabling psychiatric condition in which physical activity provides clinical benefits. While exercise effectively alleviates depressive symptoms, its biological mechanisms remain unclear.

This systematic review investigated the neurobiological effects of physical exercise on biomarkers in adults with MDD through randomized controlled trials, including studies assessing exercise interventions and reporting data on their biological effects.

A total of 30 studies, including 2194 participants, were included, examining the effects of physical exercise on various biological systems in patients with MDD. Exercise interventions had mixed effects on inflammatory markers, including interleukins, C-reactive protein, and tumor necrosis factor-α, suggesting a potential but inconsistent anti-inflammatory role. Neurotrophic factors, such as brain-derived neurotrophic factor showed promise as biomarkers of treatment response, but their role in clinical improvements remained inconclusive. Findings for the stress-response system, including cortisol and monoaminergic systems, primarily involving serotonin and dopamine, were limited and variable. Exercise demonstrated potential benefits in reducing oxidative stress and enhancing β-endorphin levels, although these effects were not consistently observed.

This systematic review adopted a broader perspective than prior studies, exploring less-studied biological systems and identifying several limitations in the included studies, including small sample sizes, varying methodologies, and a predominant focus on biochemical markers. Future research should prioritize larger, standardized trials and particularly employ omics approaches to better understand the biological mechanisms underlying the effects of exercise in MDD. The findings highlight the complexity of exercise’s biological effects and emphasize the need for further research to clarify its mechanisms.