Environmental adversity is linked to major depressive disorder (MDD), potentially via sustained low-grade inflammation. However, serum markers such as C-reactive protein (CRP) are transient and sensitive to acute states. In contrast, epigenetic signatures of inflammation may provide a more stable trace of how stress becomes biologically embedded and contributes to depression risk over time.

In a subsample of the Marburg-Münster Affective Disorders Cohort Study (MACS; N = 579; 320 healthy controls, 259 with MDD), we examined whether early life adversity (ELA; CTQ) and recent life stress (RLS; LEQ) are associated with CRP-related DNA methylation (CRPm) at baseline. We further tested whether CRPm predicts depressive symptom severity (HAMD) at baseline and at two-year follow-up (n = 407). DNA was extracted from whole blood, and CRPm scores were computed using publicly available genome-wide summary statistics.

CRPm explained 21.3% of the variance in serum high-sensitivity CRP (hsCRP). Higher CRPm was significantly associated with both ELA (b = 0.01, SE = 0.003, p = 0.017) and RLS (b = 0.01, SE = 0.004, p = 0.032), after adjusting for age and sex. CRPm also predicted depressive symptom severity at baseline (b = 0.68, SE = 0.27, p = 0.013) and at follow-up (b = 0.79, SE = 0.25, p = 0.002). These associations remained after controlling for white blood cell-type composition but were attenuated after adjusting for BMI and smoking. In contrast, hsCRP was not associated with adversity or depressive symptoms.

Our study indicates that a methylation-based index of chronic inflammation is associated with stress exposure and depressive symptoms over time, in contrast to fluctuating serum hsCRP. The findings are more consistent with an indirect pathway in which environmental adversity is linked to inflammatory biology via stress-related health behaviors, rather than with a model of direct biological embedding.

Major traumatic life events are risk factors for stress-related neuropsychiatric disorders, often accompanied by systemic inflammation, neuroinflammation, and microglial priming. As systemic inflammation, neuroinflammation, and microglial priming are considered risk factors for developing stress-related psychiatric disorders, one novel therapeutic strategy is to identify interventions that mitigate these responses. In this study, we investigated the effects of a novel soil-derived Mycolicibacterium, Mycolicibacterium sp. strain KGA-10, on in vitro immunoregulatory potential in murine bone marrow-derived dendritic cells (BMDCs) and on biomarkers of systemic inflammation, biomarkers of hippocampal neuroinflammation and microglial priming, and anxiety-like defensive behavioral responses in adult male rats exposed to inescapable tail-shock stress (IS). In Experiments 1, 2, and 3, BMDCs were exposed to the type strain, Mycolicibacterium vaccae ATCC 15483 (0, 10, 30, 100, 300 µg/mL; Experiment 1) or M. sp. strain KGA-10 (100 µg/mL; Experiments 2 and 3) or sterile borate-buffered saline (BBS) vehicle followed, 24 h later, by exposure to lipopolysaccharide (LPS; 250 ng/mL) or a cell culture media vehicle, then, 24 h later, assessed for Il10, Il12a, and Il12b mRNA expression. Exposure of murine BMDCs to M. vaccae ATCC 15483 or M. sp. strain KGA-10 induced an immunoregulatory phenotype, characterized by increased ratios of Il10:Il12a and Il10:Il12b mRNA expression in both naïve and lipopolysaccharide- (LPS; 250 ng/mL) challenged conditions. In Experiment 3, adult male rats received weekly injections of heat-killed M. sp. strain KGA-10 (0.1 mg/0.1 mL, s.c.) or sterile BBS vehicle over three weeks prior to IS. Anxiety-like defensive behavioral responses were assessed 24 h following IS or home cage control conditions using the juvenile social exploration (JSE) test, while biomarkers of hippocampal neuroinflammation and microglial priming were assessed using real-time reverse transcription - polymerase chain reaction (real-time RT-PCR). M. sp. strain KGA-10 treatment promoted an anti-inflammatory immunophenotype, evidenced by decreased hippocampal Il12a, and decreased biomarkers of microglial priming, Nfkbia and Nlrp3 mRNA expression among rats exposed to IS, in association with prevention of IS-induced increases in anxiety-like defensive responses in the JSE test. These findings suggest that M. sp. strain KGA-10 is a promising candidate for a novel intervention for promotion of stress resilience and prevention of stress-related psychiatric disorders.

Individuals with Posttraumatic stress disorder (PTSD) can experience significant emotion dysregulation and interpersonal impairments, with emerging evidence implicating alterations in empathy as a contributing factor. Prior research links specific empathy dimensions (e.g., personal distress, perspective taking) to psychopathology; however, little is known about how patterns across empathy dimensions may map onto distinct profiles, which in turn may be related to different clinical outcomes. The identification of empathy profiles in PTSD could provide the opportunity to tailor trauma interventions to specific patterns of empathic responding and improve interpersonal functioning. Therefore, this study aimed to identify empathy profiles in PTSD and their associations with emotion dysregulation and related clinical symptoms.

Participants were 108 adults with PTSD (77.8% female; mean age = 38.76) seeking trauma-focused treatment. K-means cluster analysis on the Interpersonal Reactivity Index empathy subscales identified empathy profiles. Linear models compared profiles on clinical measures (childhood trauma, depression, anxiety, PTSD symptoms, dissociation, emotion dysregulation).

Three profiles emerged: High Empathy /Moderate Distress (32.4%), Moderate Empathy/Low Distress (38.0%), and Low Perspective-Taking/High Distress (29.6%). Follow-up univariate tests showed profiles differed significantly in depression, anxiety, and emotion dysregulation but not trauma history, PTSD symptoms, or dissociation. Emotion dysregulation differences remained significant after controlling for clinical and demographic covariates.

We identified novel empathy profiles in PTSD that show differential associations with emotion dysregulation and psychopathology. Emotion dysregulation emerged as the primary clinical correlate distinguishing these profiles, suggesting it may represent a key mechanism linking empathic patterns to functional outcomes.

Perioperative depressive symptoms (PDSs) are common among patients who undergo major surgery and can lead to worse clinical outcomes. Esketamine has been reported to alleviate PDSs in patients undergoing certain types of surgery. However, there is a lack of evidence from large-scale, multisurgery studies to support its therapeutic effects in individuals with preexisting moderate-to-severe PDSs. Thus, we designed this multicenter, randomized, placebo-controlled and double-blinded trial to investigate whether esketamine is associated with greater improvements than the placebo among patients undergoing major surgery. Patients with moderate-to-severe PDSs who underwent major surgery were assessed for eligibility and randomly assigned to receive esketamine or placebo intraoperatively. The primary outcome was the remission rate 3 days after surgery, which was defined as a Montgomery-Åsberg Depression Rating Scale score less than or equal to 10. The secondary outcomes included pain, esketamine-related psychotic symptoms and safety outcomes after surgery. A total of 435 patients were randomized to receive either esketamine (n=218) or placebo (n=217). The remission rate was greater in the esketamine group than in the placebo group at 3 days post-surgery (28.3% vs. 11.3%; OR 3.12 [95% CI, 1.79-5.55]; P <0.001). The rates of acute pain were similar between the two groups. Intraoperative treatment with esketamine resulted in a greater proportion of participants whose depressive symptoms improved, but careful monitoring was necessary because of the possibility of developing dissociative symptoms. The clinical application of esketamine for depressive symptoms should consider its benefits and risks in the future. TRIAL REGISTRATION: Clinicaltrial.gov NCT04425473. LIST OF CHEMICAL COMPOUNDS: Esketamine (PubChem CID: 182137) and Ketamine (PubChem CID: 3821).

Obsessive-compulsive disorder (OCD) may develop following brain lesions, but lesion distribution and connectivity patterns are unknown.

Cases of OCD associated with focal brain lesions were identified using a systematic literature search and compared to control lesions (N=608). Connectivity with each lesion location was computed using normative functional connectivity (N=1000) and a network specific to OCD lesions was identified. The relevance of this network for primary OCD was explored.

Among 129 cases of lesion-associated OCD, 40 had clearly defined locations. OCD-associated lesions intersected the orbitofrontal cortex and right temporal pole more than control lesions and were associated with connectivity to a distinct brain network. This network overlapped with abnormal functional brain imaging and with effective brain stimulation targets in primary OCD.

Lesion locations associated with OCD map to a common brain network that aligns with brain imaging abnormalities and brain stimulation outcomes in patients with primary OCD.

The longitudinal relationship between depressive symptom trajectories and osteoarthritis (OA) remains poorly understood. We aimed to investigate the association between distinct temporal patterns of depressive symptoms and the risk of incident osteoarthritis across three large, internationally diverse aging cohorts.

This study utilized data from 18,688 middle-aged and older adults without osteoarthritis at baseline from the China Health and Retirement Longitudinal Study (CHARLS, N = 5143), the Health and Retirement Study (HRS, N = 8036), and the English Longitudinal Study of Aging (ELSA, N = 5509). Depressive symptom trajectories were identified using a deterministic binary concatenation approach over three assessment waves (approximately 4-5 years of follow-up per cohort). Multivariable logistic regression models assessed associations between trajectory patterns and incident osteoarthritis, adjusting for demographic factors, lifestyle behaviors, and comorbidities. Subgroup analyses examined potential effect modification by age, sex, and clinical characteristics.

Four distinct depressive symptom trajectories were identified across cohorts: no/minimal symptoms, decreasing symptoms, increasing symptoms, and persistent symptoms. Compared to those with minimal symptoms, participants with persistent depressive symptoms demonstrated significantly elevated osteoarthritis risk in CHARLS (OR = 2.25, 95% CI: 1.78-2.83), HRS (OR = 1.43, 95% CI: 1.16-1.77), and ELSA (OR = 1.58, 95% CI: 0.70-3.55). The increasing trajectory also conferred substantial risk across all three cohorts (CHARLS OR = 1.59; HRS OR = 1.72; ELSA OR = 2.16, all P < 0.05). Significant dose-response relationships were observed in all cohorts (P for trend <0.001). Subgroup analyses revealed important effect modification: alcohol consumption and diabetes in CHARLS (P for interaction = 0.007 and 0.035), male sex and alcohol use in ELSA (P for interaction <0.001 and 0.027), and age in HRS (P for interaction = 0.045).

Adverse trajectories of depressive symptoms, particularly persistent and increasing patterns, are consistently associated with elevated osteoarthritis risk across diverse populations. These findings underscore the importance of longitudinal mental health monitoring and suggest that early intervention for depressive symptoms may represent a modifiable pathway for osteoarthritis prevention. The observed effect modification patterns highlight the need for population-specific and personalized approaches to integrated mental and musculoskeletal health management.

Although perceived maternal psychological control (pMPC) and fear of negative evaluation (FNE) are both well-established correlates of social anxiety, their longitudinal interplay with social avoidance remains poorly understood. The present study examined the temporal associations between pMPC, FNE, and social avoidance in a three-wave longitudinal design METHODS: Participants were 608 adolescents aged 10-16 years (M_age = 12.89) who completed self-report measures at three time points over six months. Cross-lagged panel models with latent variables were estimated, and multigroup analyses tested moderation by age and sex.

Across the full sample, pMPC predicted subsequent increases in FNE (T1 → T2: β = 0.04, p < .001), which in turn predicted higher levels of social avoidance (T2 → T3: β = 0.10, p < .001). The indirect effect of pMPC on avoidance via FNE was significant (p = .001), whereas the direct path from pMPC to avoidance was not significant, supporting a full mediation model suggesting an indirect prospective pathway. Bidirectional associations between FNE and avoidance further indicated a self-reinforcing anxiety process. Importantly, these associations were not uniform across groups. The mediating pathway was significant only among boys, suggesting potential sex-specific transactional dynamics.

This study is the first to longitudinally demonstrate that FNE represents a prospective pathway, though modest in effect size, linking pMPC to anxious social avoidance in youth. The findings highlight the importance of considering cognitive mediators and child characteristics when examining family influences on adolescent social anxiety.

Polyendocrine metabolic ovarian syndrome (PMOS), previously named polycystic ovary syndrome (PCOS), affects one in eight women. However, the term PCOS is inaccurate, implying pathological ovarian cysts, obscuring diverse endocrine and metabolic features, and contributing to delayed diagnosis, fragmented care, and stigma, while curtailing research and policy framing. Building on an international mandate for change, we outline an unprecedented, rigorous, multistep global consensus process for the name change. Funding and governance were established with engagement of 56 leading academic, clinical, and patient organisations. Using iterative global surveys (with responses from 14 360 people with PCOS and multidisciplinary health professionals from all world regions), modified Delphi methods, nominal group technique workshops, and marketing and implementation analyses, we identified principles prioritising scientific accuracy, clarity, stigma avoidance, cultural appropriateness, and implementation feasibility. An accurate new name was prioritised over retaining the PCOS acronym or a generic name. Implementation approaches prioritised evolution rather than transformation. Preferred terms were polyendocrine, metabolic, and ovarian, reflecting the condition's multisystem pathophysiology, and polyendocrine metabolic ovarian syndrome was the consensus new name. Accuracy was improved by omitting cysts and by capturing endocrine, metabolic, and ovarian dysfunction. A co-designed global implementation strategy, including a transition period, education, and alignment with health systems and disease classification, is under way.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric condition characterized by intrusive thoughts and repetitive behaviors that impair functioning. Although selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy are first-line treatments, 40-60% of patients achieve only partial remission, with persistent symptoms and adverse effects. This highlights the need for alternative approaches such as phytotherapy, which has shown potential neuroprotective and neurotransmitter-modulating properties.

A structured narrative review with a systematic search was conducted across PubMed, Scopus, Web of Science, and Google Scholar up to April 2025. Studies evaluating medicinal plants or phytochemicals in OCD or OCD-like behavior were included. Both preclinical in vivo and human studies were assessed. A total of 26 studies (14 preclinical, 12 clinical) were included and appraised using a multi-domain quality framework and evidence hierarchy.

Preclinical studies indicated that several plant-derived compounds influence serotonergic, dopaminergic, and GABAergic systems and reduce OCD-like behaviors. However, most relied on non-specific models such as marble-burying, limiting interpretability. Clinical evidence was limited, with few randomized controlled trials and several low-quality or observational studies. While some interventions showed symptom improvement, methodological weaknesses and small sample sizes reduced reliability.

Current evidence does not support clinical recommendations for phytotherapy in OCD. Findings remain preliminary and hypothesis-generating. Future research should focus on well-designed clinical trials, standardized formulations, and translationally valid models to establish efficacy and safety.

Since 2018, escalating armed gang violence in Haiti has caused thousands of deaths and kidnappings, the collapse of essential services, and the internal displacement of over 1.3 million people. This study documents the prevalence of post-traumatic stress disorder (PTSD) symptoms and associated factors among internally displaced people due to armed gang violence, providing essential evidence to inform clinical care and guide targeted humanitarian and mental health interventions.

We conducted a cross-sectional survey among 1541 internally displaced adults (mean age=36.4, 60.6% women). PTSD symptoms, community violence exposure, traumatic life events, and resilience were assessed. Hierarchical logistic regression examined associations between PTSD symptoms, trauma exposure, and resilience, adjusting for sociodemographic factors.

57.2% of participants reported severe PTSD symptoms, with higher prevalence in women (62.4%), individuals displaced to rural areas (69.3%), older adults, and those with lower education. Three logistic regression models examined PTSD symptoms. Life events initially increased PTSD risk (victimized: aOR=1.12; witnessed: aOR=1.07), explaining 29.8% of variance. Adding community violence raised explained variance to 49.7%, with victimization remaining significant (aOR=1.05) and witnessing non-significant. In the final model, higher resilience slightly reduced PTSD risk (aOR=0.98), while victimization and witnessing community violence increased it (aOR=1.22 and 1.06), accounting for 50.7% of variance.

Chronic armed gang violence drives high PTSD rates among Haiti's internally displaced persons, with resilience offering limited protection. Addressing this crisis requires integrating mental health into humanitarian efforts, strengthening community support, prioritizing vulnerable groups, ensuring that psychological wellbeing becomes a central pillar of recovery and social stability.