This study aimed to examine sex-specific alterations in structural brain network organization across different stages of major depressive disorder (MDD) and to explore whether stage-related network changes are associated with relapse risk in female patients. Diffusion tensor imaging and graph-theoretical analyses were performed in 90 first-episode, drug-naïve patients with MDD (31 males, 59 females) and 50 matched healthy controls. Patients were followed for up to 12 months, with repeat imaging during remission and clinical assessment for relapse. Structural networks were reconstructed using deterministic tractography. Network measures included rich-club, feeder, and local connections. Group differences were assessed using general linear models with false discovery rate correction. Linear mixed-effects models were applied to account for within-subject dependence across disease stages. Associations with clinical outcomes were examined using partial correlation and receiver operating characteristic analyses. Acute-phase rich-club disruption occurred in both sexes but was more severe in females (all P < 0.05). During remission, males showed robust compensatory recovery, exceeding control levels (P < 0.05), whereas females exhibited only partial restoration. Critically, reduced rich-club connections during remission were associated with 12-month relapse in females, a relationship absent in males (AUC = 0.836, P < 0.001). Mixed-effects models yielded convergent patterns across network measures (all P < 0.05). These findings suggest different patterns of structural network change across disease stages in male and female patients with MDD. Rich-club connections may reflect aspects of structural network recovery and be associated with differences in relapse risk following remission across sexes.

Bipolar disorder (BD) is a major psychiatric condition with a multifaceted and largely unknown pathophysiology. Mania, the defining feature of BD, remains underinvestigated. Proteomics offers a powerful, data-driven, unbiased approach to uncover biological alterations. Blood platelets provide a stable and comprehensive reflection of the body's internal milieu. This proof-of-concept study explores platelet proteomic alterations in mania. High-resolution proteomic profiling was performed on platelet samples from hospitalized patients with severe mania (n = 11) and 1:1 age- and sex-matched healthy controls (n = 11) using liquid chromatography-tandem mass spectrometry. Platelet proteins were quantified, differentially expressed proteins identified, and functional enrichment analyses conducted to characterize associated biological pathways. Key proteomic predictions were validated by enzyme-linked immunosorbent assay (ELISA) in platelet and plasma samples. Proteomic analysis revealed that mania is associated with proteins primarily enriched in immune activation while lacking those enriched in cell homeostasis. Among shared proteins, mania exhibited a prominent cluster of downregulated proteins, primarily converging on immune-related pathways. The most robust alteration involved deficits in MHC Class I-mediated antigen processing. Key immune regulatory hubs - transforming growth factor (TGF)-β and interleukin-4 (IL-4) - were identified, with the association of increased TGF-β levels with mania validated by ELISA. This study highlights platelet proteomics as a valuable tool for investigating biological alterations in psychiatric disorders. Our findings indicate deficits in MHC Class I-related pathways and immune alterations consistent with chronic low-grade inflammation, suggesting potential roles for latent viral and autoimmune-related mechanisms in BD. These results support and refine the concept of immune dysregulation in mania and BD.

This study aimed to assess the associations between particulate matter (PM) exposures and depressive symptom trajectories, as well as the potential contributing role of loneliness in these associations. The analysis included 11,758 participants (≥45 years), with depressive symptoms and covariate data from the China Health and Retirement Longitudinal Study (2011-2020) and PM data from the ChinaHighAirPollutants dataset. Depressive symptom trajectories were identified using group-based trajectory modeling. Individual and combined effects of PM on depressive symptom trajectories were assessed using multivariable logistic regression and weighted quantile sum (WQS) regression, with results reported as odds ratio (OR) and 95% confidence interval (CI). A serial multiple mediator model was used to evaluate the contributing role of loneliness. Five depressive symptom trajectories were identified: stable-low, stable-moderate, stable-high, decreasing, and increasing. PM exposures were positively associated with more severe depressive symptom trajectory groups (stable-high [PM10: OR = 1.10, 95% CI 1.04-1.16; WQS: OR = 1.41, 95% CI 1.09-1.82] and increasing [PM1.0: OR = 1.44, 95% CI 1.06-1.98; PM2.5: OR = 1.10, 95% CI 1.02-1.19; PM10: OR = 1.10, 95% CI 1.06-1.13; WQS: OR = 1.21, 95% CI 1.01-1.45]) compared to the stable-low symptoms trajectory. Loneliness contributed to 26.73%-29.73% of the associations between PM exposure and depressive symptom trajectories. Exposures to individual and mixed PM pollutants increase the risk of severe depressive symptom trajectory groups, and reducing loneliness alleviates these effects. The findings underscore the need for further coordinated control of PM pollutants and alleviating loneliness to prevent depressive symptoms.

Despite the widespread clinical use of psychotherapy, the neural mechanisms linking treatment to changes in inhibitory control networks supporting self-regulation remain unclear. This study addresses this gap by meta-analyzing neuroimaging research on how psychotherapy affects brain regions involved in inhibitory control. We conducted a systematic literature review, selecting functional magnetic resonance imaging (fMRI) studies that examined inhibitory control tasks before and after psychotherapeutic interventions. Fifteen studies met the inclusion criteria and were analyzed using the activation likelihood estimation (ALE) algorithm. Results revealed three significant clusters of activations, namely: the superior and medial frontal gyrus (including pre-supplementary motor area), anterior cingulate cortex (ACC), and subcortical regions, such as the thalamus and globus pallidus. These areas are commonly reported as key nodes of the inhibitory control brain network. Overall, our main result indicates that psychotherapy might modulate key brain region activations involved in inhibitory control, particularly the prefrontal cortex-anterior cingulate network. This suggests that psychotherapy enhances cognitive and emotional regulation through strengthening inhibitory mechanisms. Moreover, the observed neural changes appear to parallel those induced by pharmacologic interventions, pointing to potential convergent therapeutic targets despite differing mechanisms of action.

Adolescent pregnancy is a global public health concern associated with increased risks of physical health, mental well-being, and social functioning; however, its potential to increase the long-term risk of major psychiatric disorder (MPD) remains underexplored. Between 1996 and 2013, a cohort of 29,974 girls with adolescent pregnancy without MPD before and 1:4 matched controls based on age, family income, residence location, and individual psychiatric comorbidity were enrolled. A Cox regression model was used, adjusted for potential confounders, to estimate the risk of schizophrenia, bipolar disorder, and major depressive disorder (MDD). After adjusting for confounding factors, adolescent pregnancy was associated with significantly increased risks of bipolar disorder (hazard ratio 1.44; 95% confidence interval 1.20-1.72) and MDD (1.88; 1.76-2.00), but not schizophrenia (0.94; 0.73-1.21), compared to the control group. These associations persisted after excluding the first 3 years of follow-up, with elevated risks of bipolar disorder (1.27; 1.05-1.54) and MDD (1.61; 1.50-1.72) among adolescents with pregnancy compared to controls. These results underscore the importance of implementing long-term mental health surveillance strategies for young mothers who experience adolescent pregnancy.

We aimed to examine the psychometric properties of the second version of the Brief Evaluation of Psychosis Symptom Domains (BE-PSD-V2.0) and its correspondence with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity scale (CGI-S) scores. This cross-sectional study was conducted at 18 institutes in Japan. We performed correlational analyses to test the convergent and divergent validity of the BE-PSD-V2.0. Inter-rater reliability was assessed using intraclass correlation coefficients (ICCs). The equipercentile equating method was employed to examine the linking of the BE-PSD-V2.0 with the PANSS and the CGI-S. A total of 353 patients with schizophrenia spectrum disorders were included. Spearman's rank correlation coefficients between the BE-PSD-V2.0 item scores and their corresponding PANSS factor scores ranged from 0.64 to 0.86, indicating sufficient convergent validity. These specific correlation coefficients were consistently the highest among all item-to-factor comparisons, indicating sufficient divergent validity. In 34 patients, ICCs for the BE-PSD-V2.0 itemand total scores ranged from 0.60 to 0.94, showing sufficient inter-rater reliability. Conversion tables were established between the BE-PSD-V2.0 total score and the PANSS total score, between the BE-PSD-V2.0 total score and the CGI-S score, and between the BE-PSD-V2.0 item scores and their corresponding PANSS factor scores. A correspondence between symptomatic remission criteria using the PANSS and BE-PSD-V2.0 was confirmed. The BE-PSD-V2.0 possesses sufficient psychometric properties and corresponds to the PANSS and CGI-S. It is a sound and reliable brief rating scale for assessing symptoms in schizophrenia spectrum disorders, and its established conversion correspondences facilitate score interpretation within existing clinical paradigms for both clinical practice and research.

Adherence to the Mediterranean-dietary approaches to stop hypertension (DASH) intervention for neurodegenerative delay (MIND) diet has been associated with a reduced risk of dementia, yet clinical and mechanistic evidence is limited. This study aims to explore the relationship between MIND diet adherence and cognitive function in Alzheimer's disease (AD), with a specific focus on resting-state EEG to investigate the underlying mechanisms. We evaluated 841 memory clinic participants: 119 cognitively normal, 255 with mild cognitive impairment, and 467 with AD. Cognitive, dietary, neuropsychiatric, and functional data were collected. EEG from 204 participants was analyzed for spectral and connectivity features. MIND scores were significantly lower in the AD group (P < 0.001). Higher MIND adherence was linked to better global cognition, lower dementia severity, fewer mood symptoms, and greater daily functioning (P < 0.05). Individuals in the lowest adherence tertile had 6.78 times higher odds of cognitive impairment compared to those in the highest tertile (OR = 6.78, 95% CI: 4.54-10.13, P < 0.001). EEG analyses revealed that greater MIND adherence was associated with increased alpha power, reduced occipital theta/beta and delta/alpha ratios, and stronger frontoparietal connectivity. Mediation analysis indicated that frontal and global alpha power partially mediated the associations between MIND diet adherence and dementia severity, mood symptoms, and functional status. High MIND adherence is associated with improved cognitive and functional outcomes in AD. EEG signatures may partially mediate these effects, highlighting the clinical potential of the MIND diet for early intervention and neurophysiological monitoring.

Inflammatory factors interact with brain imaging-derived phenotypes (IDPs); however, the specific causal relationships between inflammatory factors and brain white matter (WM)-related IDPs remain unclear. Thus, we sought to analyze the potential causal effects of inflammatory factors on brain WM-related IDPs using Mendelian randomization (MR). We obtained the data of 41 inflammatory factors from a genome-wide association study (GWAS) from the Cardiovascular Risk in Young Finns Study and the FINRISK surveys, as well as the data of 144 neurite orientation dispersion and density imaging (NODDI) IDPs including intracellular volume fraction (ICVF), isotropic volume fraction (ISOVF), and orientation dispersion index (ODI) from the United Kingdom Biobank (UKB). We then conducted two-sample MR analyses to examine their causal interactions by employing the inverse variance weighting (IVW), MR Egger, weighted median, simple mode, and weighted mode methods, collectively enhancing the robustness of our results. Besides, bibliometric analysis was employed to investigate the overview of inflammatory factor-brain WM research. Pronounced correlations are discerned between extensive inflammatory factors and NODDI IDPs, primarily involving cerebellar peduncle, corpus callosum, uncinate fasciculus, posterior thalamic radiation, posterior corona radiata, medial lemniscus, superior longitudinal fasciculus, superior fronto-occipital fasciculus, and internal capsule. Besides, bibliometric analysis demonstrates that microglia play an important role in inflammation-mediated white matter changes. This study identified genetic evidence indicating that dysbiosis of inflammatory factors exerts causal effects on microstructural diffusion properties of brain WM. Our findings provide novel insights into the diagnostic and therapeutic management of central nervous system (CNS) disorders.

Schizophrenia is associated with subtle brain structural alterations, but separating disease from medication effects is challenging. Antipsychotic dopamine D2 receptor (D2R) antagonism has been associated with striatal volume increases, but effects of partial D2R agonism by newer antipsychotics are largely unexplored. This study aimed to compare short-term brain changes associated with either D2R antagonism or partial D2R agonism using normative modeling. Secondarily, the study aimed to explore long-term effects following naturalistic treatment. Antipsychotic-naïve patients with first-episode psychosis received 6 weeks of monotherapy with either amisulpride (D2R antagonist) (N = 41) or aripiprazole (partial D2R agonist) (N = 45). All patients underwent structural magnetic resonance imaging before and after 6 weeks of treatment. A subset was re-scanned at 6 months, 1 year, and 2 years of naturalistic treatment. A pretrained normative model was applied to 186 subcortical and cortical regions. We used Wilcoxon signed-rank tests to identify longitudinal structural deviations. Amisulpride and aripiprazole were associated with striatal volume increases after 6 weeks. No cortical effects were observed with amisulpride. Thinning of the temporal lobe was observed with aripiprazole. After 6 months, and 1 and 2 years, the striatal changes abated but cortical thinning in the frontal lobes emerged. Both partial D2R agonism and D2R antagonism appear linked to striatal volume increases; however, changes appear transient. Conversely, frontal thinning occurs over time and appears less closely linked to antipsychotic treatment. Interpreting structural brain changes in patients with psychosis require consideration of short-term pharmacological effects as well as factors related to illness progression.