Gendered racism, rooted in the interlocking injustices of racism and sexism, is a contributor to poor mental health; its association with physical health outcomes, however, is not well understood. This study investigates whether gendered racism is associated with disease activity among Black women living with systemic lupus erythematosus (SLE). Data are from the Vascular Aging, Inflammation, and Stress in African American Women's Health Research Study (VISTA; 2017-2023). Analyses were restricted to Black women with SLE (N = 201). Results revealed more frequent gendered racism experiences were associated with greater disease activity; this association was attenuated yet remained significant after adjustment for depressive symptoms. Gendered racism experiences linked to Assumptions of Beauty and Sexual Objectification were most consistently associated with disease activity. Study results underscore the importance of examining intersectional injustice (e.g., gendered racism) as a social determinant of health.

Climate change (CC) poses risks to mental health, with pregnant women highly vulnerable due to unique physiological, emotional, and social changes. This study explored the relationship between cognitive appraisal of CC, emotional responses (e.g. eco-anxiety and solastalgia), and pro-environmental actions and mental well-being in 27 pregnant women in Canada. We used validated online surveys including measures of depressive symptoms and generalized and pregnancy-related anxiety (PRA). Results indicate that cognitive appraisal of CC showed a significant direct effect on anxiety severity when adjusted for all covariates. Eco-anxiety was significantly associated with all mental health measures, while solastalgia was significantly associated with P-RA. Pro-environmental actions showed no significant association. Contextual factors did not modify these relationships. These findings highlight that emotional responses to CC, rather than cognitive appraisal or actions, are important predictors of mental health during pregnancy, warranting further research in larger, diverse populations, particularly in regions severely affected by CC.

OBJECTIVES: This research examined the associations between neighborhood physical disorder and social participation among community-dwelling older adults, and whether low social cohesion, as a social-relational pathway, and depressive symptoms, as a psychological pathway, partially explain the associations. METHODS: Using national data from Rounds 12-14 of National Aging and Trends Study, this research involved 3,350 Americans aged 65 or older. Social participation was measured by self-reported participation in five informal and formal social activities. Linear regressions examined associations between physical disorder and social participation, both cross-sectionally and longitudinally. A lagged dependent variable was included in the longitudinal models. Path analysis examined whether low socia l cohesion and depressive symptoms mediated the associations. RESULTS: Living in neighborhoods with physical disorder was associated with reduced social participation over time, yet the strength of the associations weakened over time. Low social cohesion mediated the association between physical disorder and social participation in Rounds 12 and 13, whereas depressive symptoms partially explained the association between physical disorder and social participation in Round 13 only. No longitudinal mediation was found. DISCUSSION: The findings highlight the important role of neighborhood physical disorder in social participation in later life, with associations that may be attributed to lower social cohesion and more depressive symptoms.

The link between neurodevelopmental and psychiatric conditions is increasingly recognized in developmental psychiatry, yet the relationship between Autism Spectrum Disorder (ASD) and Personality Disorders (PDs) remains underexplored in adolescence. Dysfunctional personality traits (DPT) may emerge in individuals with ASD, especially when diagnosis is delayed and comorbidities occur. This study assessed 79 adolescents (mean age = 15.15 ± 1.50; 45.6% females) with ASD without intellectual disability using a multimodal protocol (Autism Diagnostic Observation Schedule-Second Edition [ADOS-2], Autism Diagnostic Interview-Revised [ADI-R], Wechsler Intelligence Scale for Children-Fourth Edition [WISC-IV]/Wechsler Adult Intelligence Scale-Fourth Edition [WAIS-IV], Structured Clinical Interview for DSM-5 Personality Disorders [SCID-5-PD], Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version [K-SADS-PL], standardized questionnaires). Analyses examined associations between DPT, psychiatric comorbidities, clinical severity, and functioning. DPTs were identified in 64.5% of participants, more frequently in females (75.0%) than males (48.9%). A prior ASD diagnosis was missing in 62%, particularly among females (odds ratio [OR] = 2.86,  = .030). Cluster A traits were most common (38.0%), notably Schizoid (22.8%), followed by Cluster B (24.1%), with Borderline traits markedly higher in females (22.2% vs. 2.3%,  = .006) and Cluster C (20.3%). DPTs were associated with lower functioning (Children's Global Assessment Scale [CGAS],  = .037) and higher clinical severity (Clinical Global Impression [CGI],  < .019), also after False Discovery Rate (FDR) correction. Findings indicate that DPTs are highly prevalent yet often unrecognized in adolescents with ASD and are associated with greater comorbidity and poorer psychosocial outcomes. Early, developmentally informed assessment is crucial to identify risks and guide tailored interventions.Lay AbstractAutism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social communication, behavior, and sensory processing. Some autistic adolescents may also show emerging maladaptive personality traits or early features of personality pathology. However, the relationship between ASD and personality disorders has been studied far less than other mental health conditions, especially during adolescence, a key developmental stage. This study included 79 adolescents with ASD without intellectual disability, with an average age of 15 years. Nearly half of the participants were female. Each adolescent completed a comprehensive clinical assessment, including standardized tools for autism diagnosis, psychiatric diagnostic interviews, cognitive testing, and questionnaires on emotional and behavioral functioning. We found that almost two-thirds of participants showed dysfunctional personality traits (DPTs). These traits were more common in females than males. In addition, many adolescents had not received an autism diagnosis before entering the study, and missed or delayed diagnosis was especially frequent among females. This is consistent with growing evidence that autism in girls may be less easily recognized, particularly when symptoms are masked or present differently from traditional expectations. The most common personality patterns involved social withdrawal, emotional detachment, and limited interest in close relationships. Other adolescents showed traits linked to emotional dysregulation, impulsivity, anxiety, perfectionism, or a strong need for control. Adolescents with DPTs also showed greater overall clinical severity and lower psychosocial functioning in everyday life, including difficulties with peers, family relationships, and school adjustment. These findings suggest that emerging personality pathology is common but often overlooked in autistic adolescents. If autism is identified late, emotional and interpersonal difficulties may become more complex over time. Clinicians should assess autistic traits, co-occurring psychiatric symptoms, and maladaptive personality features together, using a developmentally informed approach. Earlier and more accurate recognition may support personalized interventions, reduce distress, and improve outcomes during the transition to adulthood.

OBJECTIVE: Ketamine is a rapid-acting antidepressant with an incompletely understood mechanism of action. Pharmacometabolomics can identify pathways underlying its effects and response variability. Using data from the Bio-K trial (NCT03156504), a multisite open-label study, we characterised metabolomic signatures of intravenous (IV) racemic ketamine in adults with treatment-resistant depression (TRD). METHODS: Sixty-nine adults with TRD and major depressive disorder received three ketamine infusions (0.5 mg/kg). Remission was defined as MADRS ≤9 at 24 h post-third infusion. Metabolomic profiling used the Biocrates MxP® Q500 kit (>600 metabolites). Mixed-effects models assessed changes across time points (pre-dose, post-infusion 1, post-infusion 3), adjusting for age, sex, infusion length (first), and body mass index, with false discovery rate correction. RESULTS: Mean MADRS improved from 27.8 ± 5.8 to 11.1 ± 9.1 post-third infusion ( < 0.001); 54% achieved remission. Post-infusion 1, ketamine was associated with increased acylcarnitines, cortisol, amino acids (glutamine, glycine, BCAAs), and biogenic amines (GABA, putrescine), with reduced medium-chain acylcarnitines and glutamate. Post-infusion 3, C16, serotonin, and GABA elevations persisted while cortisol normalised. Remitters showed greater GABA synthesis increases, however, no metabolite change correlated with MADRS improvement after correction for multiple testing. CONCLUSIONS: Ketamine exposure was correlated with broad metabolic alterations spanning mitochondrial activation, neurotransmitter modulation, and neuroendocrine signalling. These findings represent metabolic correlates of ketamine exposure and remission, rather than validated predictors or established mechanistic drivers of antidepressant response. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03156504.

PURPOSE: The Manchester Short Assessment of Quality of Life (MANSA) is a quality-of-life (QOL) instrument developed for people with mental illness. This study aimed to develop a Japanese version of the MANSA for people with severe mental illness (SMI) and examine associations between individual MANSA domains and psychiatric diagnosis. METHODS: The MANSA includes 12 self-rated subjective QOL items; the overall score is their mean on a 1-7 scale. We prepared a Japanese translation and tested validity and reliability using cross-sectional survey data from 237 adults with SMI in Japan. Concurrent validity was tested in 38 respondents who also completed the WHOQOL26. The sample was randomly split for exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) in separate subsamples. Analyses included score distributions, validity, internal consistency, and domain-level ordinal logistic regression. RESULTS: The MANSA items showed the expected associations with the relevant scales and items. Although a two-factor structure was supported by EFA, the CFA fit indices were CFI = 0.86, TLI = 0.82, and RMSEA = 0.12. In the one-factor EFA solution, all factor loadings exceeded 0.40. Cronbach's alpha for all 12 items was 0.877. The schizophrenia-spectrum group had higher scores in several domains than the bipolar- and depressive-disorder groups, and symptom stability was associated with higher scores across all domains. CONCLUSIONS: The Japanese version of MANSA showed acceptable concurrent validity and internal consistency. The proposed two-factor structure was not supported; total-score use remained reasonable, but further validation is needed. Diagnosis and symptom stability were associated with domain-specific QOL.

Asthma is a common chronic respiratory condition that significantly affects the quality of life, academic performance, and mental health of college students. Among those living in hostels, these challenges are often amplified by environmental triggers such as poor ventilation, dampness, mold, and temperature-related conditions, as well as psychosocial stressors linked to communal living. This perspective explores the overlooked intersection between asthma management, mental well-being, and institutional responsibility within hostel settings. It discusses how corticosteroid therapy, while essential for disease control, may contribute to psychiatric symptoms that further complicate adherence and daily functioning. Many students experience stigma, embarrassment about inhaler use, and inadequate support from hostel staff during exacerbations, which collectively lead to poor control and academic decline. Addressing these issues demands a shift beyond pharmacological approaches toward comprehensive institutional strategies that include environmental assessment and remediation, appropriate indoor temperature and humidity control, routine medical screening, staff training, peer support, and digital self-management tools. By fostering awareness and integrating psychosocial support into campus health systems, colleges can create safer and more inclusive environments for students with asthma, ultimately improving both respiratory outcomes and overall well-being.

OBJECTIVES: This study examined the effectiveness of a virtual reality based nostalgic cognitive training program for older adults attending day-care centers. METHODS: In this two-arm randomized controlled trial ( = 55; mean age = 81.24 years), participants received 12 sessions of VR-based nostalgic cognitive training integrating culturally familiar Taiwanese life scenes (1960s-1990s) with structured multidomain cognitive tasks, or routine activities. The prespecified primary outcome was global cognitive function (MoCA-T). Prespecified secondary outcomes were nostalgia propensity (SNS), depressive symptoms (GDS-15), psychological well-being (PWB-18) and life satisfaction (LSI-SF). Generalized estimating equations (GEE) were used to examine intervention effects. This trial was retrospectively registered at ClinicalTrials.gov (Identifier: NCT06973551). RESULTS: Significant group × time interactions for MoCA-T, SNS, and GDS-15 favored the experimental group. No significant group × time interaction was found for PWB-18 or LSI-SF, although PWB-18 showed within-group improvement in the experimental group. CONCLUSIONS: VR-based nostalgic cognitive training may provide short-term benefits for global cognitive function, nostalgia propensity, and depressive symptoms among older adults in day-care settings.

PURPOSE: Generalized anxiety disorder (GAD) impairs quality of life (QoL) and daily function; however, it remains under-recognized in Japan due to symptom overlap and a lack of approved treatments. This study estimated GAD prevalence among psychiatric outpatients using the Structured Clinical Interview for DSM (SCID), examined associated demographic and clinical factors, assessed health status and QoL, and evaluated the diagnostic validity of the Generalized Anxiety Disorder 7-item scale (GAD-7) and the Kessler 6-item Psychological Distress scale (K6) versus SCID. METHODS: This multicenter, cross-sectional study analyzed 407 patients across 22 sites. Prevalence was determined through SCID-based structured interviews. Demographics were obtained from paper questionnaires and clinical characteristics from medical records. Patient-reported outcomes quantified burden and screening accuracy. RESULTS: Eighty-three of 407 patients (20.4%) met DSM-5 criteria for GAD using SCID. Prevalence was higher in females versus males (68.7% vs 31.3%) and more common among younger individuals. Comorbid depressive disorders were frequent (63.4%), with major depressive disorder being the most prevalent. Patients with GAD were more likely to have lower income, be students, and exhibit higher symptom severity on both the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) and the GAD-7. Patients with GAD (n=83) had higher QIDS-SR, GAD-7, and K6 scores than non-GAD patients, indicating greater depressive symptoms, anxiety, and psychological distress. Health-related QoL and functional impairment measured through EuroQol 5 Dimensions 5 Levels and the Sheehan Disability Scale indicated worse outcomes in GAD. GAD-7 and K6 demonstrated moderate diagnostic performance versus SCID. CONCLUSION: GAD was prevalent among Japanese psychiatric outpatients (20.4%), suggesting the potential under-recognition in clinical practice, with some patients receiving alternative diagnoses. The lack of approved treatments and recognized diagnostic procedures may exacerbate the patient's burden. Developing GAD-specific therapies and improving diagnostic awareness are critical to addressing this unmet need.

PURPOSE: This study evaluated outcomes of venlafaxine treatment in Japanese patients with major depressive disorder (MDD) in routine clinical practice. Since anxiety is a common and clinically relevant feature of MDD, descriptive analyses were conducted based on the presence or absence of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) anxious distress. PATIENTS AND METHODS: This 12-week, multicenter, single-arm, observational study consecutively enrolled adult patients with MDD initiating venlafaxine in Japan. DSM-5 anxious distress was assessed at baseline. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 12 or discontinuation. Secondary endpoints included MADRS response and remission rates, patient-reported outcomes, and safety. Analyses were descriptive and conducted by anxious distress status. RESULTS: Among enrolled patients, 407 received venlafaxine and comprised the safety analysis set; 198 (48.6%) had anxious distress. MADRS total score decreased from baseline to week 12 or discontinuation in the overall population and in patients with and without anxious distress. Patients with anxious distress had higher baseline symptom severity but showed improvement over time. Similar improvements were seen across secondary patient-reported outcomes in both subgroups. Drug-related adverse events and discontinuations due to adverse events were numerically more frequent in patients with anxious distress. The safety profile was in line with established findings. CONCLUSION: Venlafaxine treatment in clinical practice improved depressive symptoms, anxiety, functioning, quality of life, and cognitive complaints in patients with MDD. Improvements were seen in patients with and without anxious distress. These results provide descriptive real-world evidence on treatment outcomes; however, they should be interpreted with caution given the non-comparative study design and other limitations. The findings may inform clinical decision-making in patients with heterogeneous presentations encountered in routine psychiatric practice.

BACKGROUND: Primary insomnia is associated with cognitive impairment and subtle brain structural alterations; however, the relationship between white matter microstructural damage and glymphatic-related imaging changes remains unclear. This study investigated these alterations by jointly assessing peak width of skeletonized mean diffusivity (PSMD), diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), and enlarged perivascular spaces (EPVS). METHODS: This retrospective cross-sectional study included 64 right-handed adults, comprising 32 patients with primary insomnia and 32 healthy controls. All participants underwent standardized assessments of sleep, mood, and cognition, as well as 3.0-T magnetic resonance imaging, including diffusion tensor imaging and T2-weighted imaging. PSMD and the DTI-ALPS index were calculated from diffusion data, and EPVS in the basal ganglia and centrum semiovale were visually rated. Between-group differences were evaluated using independent-samples -tests or Mann-Whitney tests with false discovery rate correction. Ordinal logistic regression was used to adjust the basal ganglia EPVS comparison for demographic and vascular risk factors. Partial correlations were adjusted for age, sex, and education, with additional analyses further adjusted for depressive and anxiety symptoms. RESULTS: Patients with primary insomnia had higher PSMD values than healthy controls (P=0.047). Basal ganglia EPVS scores were higher in the unadjusted comparison (P=0.040), but this association was attenuated after adjustment for age, education, sex, diabetes, hypertension, smoking, and alcohol consumption (odds ratio =0.329, 95% confidence interval: 0.099-1.091; P=0.069). No significant between-group differences were found in the DTI-ALPS index (P=0.267) or centrum semiovale EPVS scores (false discovery rate-adjusted P=0.211). In the full sample, higher PSMD was associated with lower DTI-ALPS values (r=-0.331, adjusted P=0.019), higher basal ganglia EPVS scores (r=0.456, adjusted P=0.001), and lower Montreal Cognitive Assessment (r=-0.329, adjusted P=0.019) and Mini-Mental State Examination scores (r=-0.440, adjusted P=0.001). These associations remained significant after additional adjustment for depressive and anxiety symptoms. CONCLUSIONS: Primary insomnia was associated with greater white matter microstructural heterogeneity, whereas evidence of glymphatic dysfunction was partial and indirect. Higher PSMD was related to glymphatic-related imaging markers and poorer cognitive performance; however, the small sample and cross-sectional design warrant cautious interpretation.

Sleep disorders are increasingly prevalent clinical conditions that significantly impair physical and mental health. Given the observed limitations of pharmacological therapies, there has been increasing research interest in effective non-pharmacological interventions. Vagus nerve stimulation (VNS), including invasive VNS and non-invasive methods such as transcutaneous auricular VNS (taVNS), has emerged as a promising neuromodulatory strategy. This review summarizes current evidence on VNS for insomnia, central hypersomnia, restless legs syndrome, and sleep-related breathing disorders, highlighting both clinical findings and proposed mechanisms. Relevant literature was identified through searches of PubMed and Web of Science up to May 2026 using terms related to VNS (eg, "vagus nerve stimulation" and "taVNS") and sleep disorders (eg, "insomnia", "narcolepsy", "hypersomnia", and "sleep-related breathing/movement disorders"). The proposed mechanisms include multilevel regulation of sleep-wake neural pathways; immunomodulation via anti-inflammatory pathways; inhibition of cortical spreading depression; and enhancement of neuroplasticity, cerebral blood flow, and blood-brain barrier integrity. Finally, we discuss key challenges regarding inter-individual variability and stimulation parameter optimization, as well as outline future directions centered on precision neuromodulation. These include the development of intelligent closed‑loop stimulation systems (ie, devices that automatically adjust stimulation parameters based on real time physiological feedback) and the testing of state dependent neuromodulation hypotheses. Taken together, this review not only summarizes current evidence but also proposes a theoretical framework and translational perspective to inform future research and clinical applications.

ImportanceSleep disturbances are highly prevalent among veterans and negatively impact mental health and occupational performance. Occupational therapy (OT) practitioners are well equipped to address sleep as a core occupation through interventions that target habits, routines, and environmental contexts.ObjectiveTo examine the feasibility and acceptability of a community-based, OT-led modified cognitive behavioral therapy for insomnia (CBT-I) program for veterans with self-reported sleep disturbances and to explore associated changes in sleep, occupational performance, and mental health outcomes.DesignSingle-arm, pre-post pilot feasibility study with exploratory quantitative analysis.SettingCommunity-based veteran organization in Montana.ParticipantsNine veterans enrolled; seven completed the 5-week program.InterventionA 5-week OT-led modified CBT-I program consisting of weekly group education and individual OT sessions.Outcomes and MeasuresSleep quality and disturbance (PROMIS-SD, PSQI), occupational performance and satisfaction (COPM), depression (PHQ-9), anxiety (GAD-7), and quality of life (SF-12). Feasibility outcomes included recruitment, attendance, retention, and acceptability as assessed via postintervention feedback survey.ResultsParticipants demonstrated improvements in sleep, occupational performance, and mental health, with no changes in health-related quality of life. Attendance and retention were high, and all participants who completed the intervention reported positive acceptability and willingness to recommend the program.Conclusions and RelevanceOT-delivered, modified CBT-I appears feasible and acceptable in community-based settings and may be associated with improvements in sleep, occupational performance, and mental health among veterans. These findings highlight the potential role of OT in expanding access to sleep interventions, particularly in rural contexts where specialized sleep services are limited.

Chronic stress facilitates the development and progression of multiple psychiatric disorders, including depression and addiction. The dysregulation of approach motivation has been proposed as a mechanism of chronic stress, but it is unclear how chronic stress is related to approach motivation. The current study sought to elucidate the relationship between chronic stress and resting-state electroencephalographic (EEG) measures of approach motivation. Sixty undergraduate students filled out the Perceived Stress Scale (PSS) and were recorded with resting-state EEG. Hierarchical regression analyses revealed significant quadratic (U-shaped) associations between mean-centered PSS scores and all three EEG measures: alpha frontal asymmetry (AFA) ( = 0.32, 95% CI [0.0001, 0.0018],  = 0.032), delta power ( = 0.33, 95% CI [0.0003, 0.0036],  = 0.021), and theta power ( = 0.31, 95% CI [0.0002, 0.0035],  = 0.030). All quadratic effects remained statistically significant after false discovery rate (FDR; Benjamini-Hochberg) correction (all adjusted  < 0.05). These findings suggest that there is a nonlinear relationship between chronic stress and approach motivation, i.e. at both low and high chronic stress levels, resting-state activation of approach motivation is enhanced, whereas at moderate chronic stress levels, approach motivation is reduced, probably reflecting more efficient allocation and conservation of brain resources. More importantly, our findings demonstrate the necessity of examining the baseline neural state in addition to the task-evoked responses when assessing stress-related changes of approach motivation, thereby providing novel insights into the mechanisms of stress adaptation and their implications for psychological health.

Maternal circadian rhythm disruption (CRD) during reproduction is increasingly recognized as a risk factor for long-term neurobehavioral disturbances in offspring. However, the stage-specific consequences of maternal CRD remain poorly understood. This study investigated the effects of maternal CRD during distinct reproductive phases, pre pregnancy mother (PPM), pregnancy mother (PM), and lactationg mother (LM) on behavioral and molecular, and structural outcomes in male offspring. Nulliparous Wistar rats were exposed to constant light (300 lx, 14 days) to induce CRD, while controls remained on a 12:12 h light/dark cycle. Male offspring were assessed for anxiety-like behavior (Elevated Plus Maze), depressive-like behavior (Forced Swim Test), hedonic behavior (Sucrose Preference Test), compulsive-like behavior (Marble Burying Test), and recognition memory (Novel Object Recognition Test). Histological analysis of the hippocampal CA1 region and expression of Brain-Derived Neurotrophic Factor (BDNF) and PER2 were also evaluated. PPM and PM offspring exhibited increased anxiety- and depressive-like behaviors, reduced body weight, alterations in hippocampal CA1 morphology, and molecular changes, including decreased hippocampal BDNF expression in the PM group and reduced SCN PER2 expression in the PPM group, without significant impairments in hedonic or recognition memory performance. In contrast, LM offspring exhibited fewer behavioral alterations compared with the other experimental groups, suggesting a differential effect of the timing of maternal circadian rhythm disruption on offspring outcomes. Considering the functional and neurodevelopmental similarities between late gestation in humans and early postnatal development in rodents, these findings suggest that the timing of maternal circadian rhythm disruption may differentially influence offspring neurodevelopment. However, because these observations were obtained in an animal model, their relevance to human pregnancy should be interpreted with caution and requires confirmation in future clinical and translational studies.

BACKGROUND: School policing has expanded dramatically in U.S. public schools, yet its mental health consequences among Hispanic adolescents remain understudied. Although a growing body of scholarship examines the educational and social outcomes of school policing for Latine youth, few studies have isolated the association between specific policing exposures and depressive symptoms in this population. PURPOSE: This study examined the association between school policing experiences, school discipline, and depressive symptoms among 15-year-old Hispanic youth, testing whether the distinction between police presence and direct police contact differentially predicts depressive symptomology. METHODS: Using data from the Year 15 wave of the Future of Families and Child Wellbeing Study (FFCWS; N = 813 Hispanic youth, 51.8% male; data collected 2014-2017), ordinary least squares regression estimated the association between five school policing and discipline indicators and a summed five-item Center for Epidemiologic Studies Depression (CES-D 5) score (α = .778). Three model specifications were estimated: unadjusted, adjusted for demographics and prior mental health, and a sensitivity analysis additionally adjusting for school connectedness. RESULTS: Being stopped by police at school was associated with 2.29 additional depressive symptom points (p < .001) after covariate adjustment-a substantively meaningful increase on a 0-15 scale. Witnessing others stopped by police was also significantly associated with higher depressive symptoms (β = 0.58, p = .007). Ambient police presence (officers stationed, security guards stationed) and school discipline showed no significant associations. Sensitivity analyses additionally adjusting for school connectedness attenuated but did not eliminate significant associations for police contact (stopped: β = 1.65, p < .001; witnessed: β = 0.45, p = .026). CONCLUSIONS: Direct police contact-both personal and vicarious-rather than ambient surveillance, appears to be the critical exposure pathway linking school policing to depressive symptoms among Hispanic adolescents. Findings support conceptualizing school police contact as a racial health stressor and underscore the need to incorporate policing exposures into adolescent health disparities frameworks.

Globally, cannabis ranks third in psychoactive substance prevalence after nicotine and alcohol, with heavy use linked to psychosis, anxiety, and depression. However, real-time data on how legal reforms influence consumption remain scarce. This Ecological Momentary Assessment (EMA) study analyzed daily cannabis use patterns before and after Germany's recreational cannabis decriminalization in April 2024 in 49 individuals (34.7% women, age 33.8 ± 11 years). Following the legal reform, a selective increase in consumed amounts among younger individuals (β = 0.01, 95%CI = 0.00-0.02, z = 3.05) was observed. Further, consumed amounts increased in outdoor (β = 0.19, 95%CI = 0.04-0.34, z = 2.51) but decreased in public settings (β = -0.46, 95%CI = -0.66 - -0.25, z = -4.36), and consumption was more likely to occur on holidays (β = 3.91, 95%CI = 1.68-9.08, z = 3.17). All ps < 0.05. By capturing the immediate post-legalization period, this study contributes to important early insights to inform prevention, treatment, and regulation.

Major depressive disorder (MDD) is a leading cause of disability worldwide, with many patients experiencing inadequate response to standard antidepressants. Dysregulation of N-methyl-D-aspartate (NMDA) receptor activity is implicated in the pathophysiology of MDD. Satoprodil (BI 1569912), an oral NMDA subunit GluN2B-selective negative allosteric modulator, was evaluated for safety and efficacy in MDD in two multicenter, randomized, placebo-controlled Phase II dose-finding trials as an adjunctive or monotherapy. In each trial, patients (18-65 years old) were randomized 2:1:1:2 to placebo or satoprodil (5 mg, 10 mg, or 20 mg) once-daily for 6 weeks, with ongoing antidepressant treatment in the adjunctive trial. Primary endpoint was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6 (both trials). Safety and tolerability were also assessed. In the adjunctive trial (N = 243; 60.9% female), the adjusted mean (standard error [SE]) change in MADRS total score at Week 6 was: placebo, -12.0 (1.1); satoprodil 5 mg, -7.8 (1.6); satoprodil 10 mg, -11.9 (1.6) and satoprodil 20 mg, -12.3 (1.2). In the monotherapy trial (N = 225; 54.2% female), the adjusted mean (SE) change in MADRS total score at Week 6 was: placebo, -10.3 (1.4); satoprodil 5 mg, -13.6 (2.1); satoprodil 10 mg, -10.6 (2.0) and satoprodil 20 mg, -10.0 (1.4). In patients with MDD, satoprodil (all doses) over 6-weeks was well tolerated but did not reduce depressive symptoms beyond placebo in either trial in a relevant manner. These trials provide the most comprehensive clinical evidence to date on GluN2B-selective modulation in MDD and will inform future research on glutamatergic pathways.

OBJECTIVE: The network theory of psychopathology proposes that dense symptom networks foster persistent symptoms. Studies testing this hypothesis in late-life depression (LLD) are lacking. This study examined whether, and how, cross-sectional networks of episodic and persistent/recurrent depressive symptoms in older adults differ. METHOD: Data of adults aged 60 + were drawn from the Survey of Health, Ageing and Retirement in Europe (SHARE). Depressive symptoms were assessed using the EURO-D scale. Participants were classified as episodic or persistent/recurrent based on their EURO-D score at wave 5 (2013) and wave 6 (2015) (EURO-D ≥4). For each group, separate cross-sectional symptom networks at wave 5 were estimated as Ising models and corrected for selection on the sum-score (Berkson's bias). The permutation-based Network Comparison Test was used to compare global strength and network structure. RESULTS: Of 8519 participants, 3746 (44.0%) participants showed episodic depressive symptoms, while 4773 (56.0%) showed persistent/recurrent depressive symptoms. Neither global network strength nor network structure differed statistically significantly between groups (p = .17 and p = .60, respectively). In both networks, lack of interest, depressive mood, and suicidality showed highest strength and expected influence. Findings were consistent across sensitivity analyses. CONCLUSION: Our results showed no difference in global strength and network structure between episodic and persistent/recurrent depressive symptoms in older adults, complementing mixed evidence from younger and middle-aged adults. Causal symptom interactions may play a smaller role in the persistence/recurrence of depressive symptoms in later life. Future studies should examine longitudinal networks, subtypes of LLD, and consider external factors.

OBJECTIVE: Delayed neurocognitive recovery (DNR) is a frequent postoperative complication in elderly patients, yet predictors in single-port video-assisted thoracoscopic (SP-VATS) lobectomy remain unclear, especially regarding psychosocial and frailty factors. We aimed to identify comprehensive preoperative and intraoperative predictors of DNR in this population. METHODS: This prospective study enrolled 309 patients aged ≥60 years undergoing SP-VATS lobectomy. Preoperative psychological status (anxiety, depression, sleep quality), physiological condition (frailty, oral health), and social support were assessed. Cognition was evaluated with the Montreal Cognitive Assessment (MoCA) at baseline, postoperative day (POD) 7, and POD 30. LASSO-penalized logistic regression and conventional logistic regression identified independent predictors. RESULTS: Overall DNR incidence was 24.60% (76/309), with 16.50% (51/309) at POD7 and 20.39% (63/309) at POD30. Univariate analysis yielded 20 significant variables. LASSO retained four candidates: Pittsburgh Sleep Quality Index (PSQI), Perceived Social Support Scale (PSSS), Surgical Apgar Score (SAS), and Hospital Anxiety and Depression Scale (HAD). Multivariable logistic regression showed higher SAS (OR=0.582, 95% CI: 0.447-0.756, P<0.001) as an independent protective factor, whereas higher PSQI (OR=2.059, 95% CI: 1.643-2.580, P<0.001) and HAD scores (OR=0.362, 95% CI: 0.161-0.813, P=0.014) were independent risk factors. The model exhibited excellent discrimination (AUC=0.919, 95% CI: 0.868-0.970), and sensitivity analyses using three alternative DNR definitions confirmed robustness (kappa: 0.61-0.82). CONCLUSIONS: Cognitive decline is common after SP-VATS lobectomy in elderly patients. DNR is influenced by psychological, physiological, social, and intraoperative hemodynamic factors. Preoperative screening for modifiable risks may reduce postoperative cognitive impairment and improve outcomes.

PURPOSE OF REVIEW: Targeting serotonergic receptors, as well as the serotonin uptake, is a relevant treatment approach for the treatment of depression. The 5-hydroxytryptamine 7 receptor (5-HTR) is a G-protein coupled receptor belonging to the serotonergic receptor family, which has received a lot of attention due to its association with mood, circadian rhythm, and cognition. This review discusses the potential of 5-HTR antagonists to treat depression, especially focusing on the pharmacological and bioengineering approaches. RECENT FINDINGS: The 5-HTR is rather common in the central and peripheral tissues, such as in the brain, gastric tract, and vascular system. It primarily signals through the Gαs/cAMP pathway, although alternative Gα12-mediated signaling has also been reported. Preclinical studies show that selective 5-HTR antagonists cause a reduction in the duration of immobility in rodent models, including the forced swim test (FST) and tail suspension test (TST), and have antidepressant-like action in the olfactory bulbectomy model of depression. Recent advances highlight the relevance of bioengineered experimental platforms and targeted drug delivery strategies to improve mechanistic understanding and optimize central nervous system (CNS)-specific modulation of 5-HTR. SUMMARY: Accumulating evidence supports the therapeutic relevance of 5-HTR antagonists in depression. Transforming receptor-delivering drug-targeted therapy together with bioengineering, human-relevant experimental models, and CNS-centred delivery systems could enhance translational understanding and therapeutic optimization. Collectively, these developments make 5-HTR antagonism a promising direction of the future antidepressant research.

BACKGROUND: Major depression (MD) is increasingly understood as a disorder characterized by widespread abnormalities in intrinsic brain functional network organization. Although both MD and brain functional connectome architecture are highly heritable, the genetic architecture underlying their relationship remains poorly characterized. METHODS: We integrated genome-wide association studies of MD with 191 ICA-based resting-state functional connectome traits to investigate their shared genetic architecture. These traits captured intrinsic connectome organization across amplitude, functional connectivity, and global connectivity domains. Cross-trait genetic analyses were used to assess pleiotropic overlap between traits. Locus-level and gene-based analyses integrating multi-omics evidence were performed to characterize the biological relevance of shared genetic signals. RESULTS: We identified significant genetic overlap between MD and 148 of 191 brain functional connectome traits. Cross-trait analyses revealed widespread shared genetic signals organized into 627 genomic loci across amplitude, functional connectivity, and global connectivity measures. Among these, 193 loci showed evidence consistent with shared causal variants based on colocalization analyses. Gene-level integration mapped these loci to 1459 protein-coding genes (390 unique genes). Multi-layer prioritization identified 17 high-confidence genes supported by convergent genomic, transcriptomic, and proteomic evidence, with enrichment in neurodevelopmental and lipid-related metabolism pathways. CONCLUSIONS: This study provides a multi-scale characterization of the shared genetic architecture between MD and intrinsic brain functional connectome organization, revealing that shared genetic signals between MD and brain functional systems are distributed across multiple functional levels and converge at the molecular level.

The normalization of ethanol consumption in Western societies represents a major public health concern, particularly when drinking begins during adolescence. The ketogenic diet (KD) has demonstrated therapeutic potential in various conditions, including substance use disorders. This, together with evidence showing that the diet does not significantly affect locomotor activity or aversive and spatial memory in adolescent male mice, makes it an interesting tool for addressing ethanol consumption during a critical developmental period: the transition from adolescence to young adulthood. However, the lack of evidence in females highlights an important gap in current research. This study aimed to evaluate the effects of a KD during adolescence on behavioral profile and ethanol consumption during young adulthood in female OF1 mice. In Experiment 1, behavioral profile was assessed after administration of a KD or control diet from postnatal day (PND) 25 to PND 48. Motor activity, anxiety-like behavior, memory, and learning were evaluated. In Experiment 2, ethanol consumption was assessed using the Drinking in the Dark and operant self-administration paradigms following dietary intervention from PND 39 to PND 82. The KD did not alter locomotion, anxiety-like behavior, or aversive memory, but enhanced hippocampus-dependent spatial memory. Molecular analyses revealed changes in gene expression, including Adora2a, Opmr1, Drd1, Cnr1, and Il-6. Additionally, KD significantly reduced ethanol consumption, which was associated with altered expression of Crhr1, Drd2, Adora2a, and Adora1. These findings support the potential of KD as a therapeutic strategy for reducing ethanol intake in females without negatively impacting behavioral development during adolescence.