Psychiatry and Clinical Neurosciences最新文献

{"title":"Early imitation predicts adaptive behavior at school age: A longitudinal population-based cohort study.","authors":"Miyuki Kondo, Asami Shinohara, Hiroki Higuchi, Tessei Kobayashi, Tomoko Nishimura, Toshiki Iwabuchi, Kenji J Tsuchiya","doi":"10.1111/pcn.70133","DOIUrl":"https://doi.org/10.1111/pcn.70133","url":null,"abstract":"<p><strong>Aim: </strong>Imitation provides a foundation for acquiring a wide range of knowledge and skills; accordingly, early imitation may contribute to the development of later adaptive behavior encompassing conceptual, practical, and social skills. The present study examined whether imitation at 14 months predicts adaptive behavior at 8 years of age in a general population sample.</p><p><strong>Methods: </strong>We analyzed data from the Hamamatsu Birth Cohort for Mothers and Children (HBC Study), a prospective birth cohort of children in Japan (n = 724). Adaptive behavior at 8 years of age was assessed using the Vineland Adaptive Behavior Scales, Second Edition (VABS-II), which served as the dependent variable. Hierarchical multiple regression analyses were conducted for each domain-level score of the VABS-II (communication, daily living skills, and socialization). Imitation at 14 months, assessed using the Japanese MacArthur Communicative Development Inventory, was entered as the primary predictor, along with relevant confounding variables.</p><p><strong>Results: </strong>The imitation score at 14 months significantly predicted all three domains of adaptive behavior at 8 years, even after controlling for covariates, including children's developmental quotient, intelligence quotient, autism spectrum disorder traits, and demographic factors. The most substantial contribution was found in daily living skills, followed by socialization and communication.</p><p><strong>Conclusion: </strong>Imitation in infancy was a significant predictor of later adaptive behavior, particularly in daily living skills and socialization. These findings suggest that early imitation may be related to learning processes essential for independent and cooperative living and may offer a clinically meaningful perspective on later functional outcomes, particularly adaptive behavior.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiation between bipolar versus unipolar depression by AI-based multimodal behavioral analysis.","authors":"Hidenori Yamasue, Sanskar Rahul Nanegaonkar, Yumi Kiyama, Mamindla Vishwa Raghava Reddy, Kotaro Ando, Shozo Kamiya, Jun Inoue, Asuka Sakurai, Tahichi Nakano, Amane Sato, Yosuke Kameno, Tomoyasu Wakuda, Keiichi Odagiri, Tadafumi Kato","doi":"10.1111/pcn.70124","DOIUrl":"https://doi.org/10.1111/pcn.70124","url":null,"abstract":"<p><strong>Background: </strong>Given their differing pathophysiology and treatment approaches, the primary aim of the current study was to develop a methodology accurately distinguishing bipolar from unipolar depression.</p><p><strong>Methods: </strong>Adults with bipolar disorder or major depressive disorder were recruited nationwide in Japan and assessed via recorded interviews. During the interview, diagnoses were established using the Structured Clinical Interview for DSM-5-Research Version. Depressive and manic symptom severity was assessed using the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS), respectively. Artificial intelligence (AI)-based integrative, quantitative analyses of behavioral characteristics, including facial expressions, eye gaze, and voice prosody, were conducted on the recorded video.</p><p><strong>Results: </strong>Between August 2022 and March 2024, 379 participants completed interviews, of whom 366 were analyzed (120 bipolar I, 93 bipolar II, 122 major depressive, and 74 persistent depressive disorder). AI-based diagnostic differentiation between bipolar and unipolar depression using four-fold, three-times repeated cross-validation achieved an overall accuracy of 78%, with an area under the curve of 0.76. Key features contributing to bipolar diagnosis included greater temporal instabilities in neutral facial expression, eye gaze, sad facial expression, and root mean square amplitude of speech. HDRS could be predicted in unipolar and bipolar depression, with influential predictors of depression including sleep inefficiency, autistic traits, variability in sad facial expression, and comorbid anxiety disorder. YMRS could be predicted with major predictors including comorbid anxiety disorder, sleep inefficiency, and variabilities in sad facial expression and eye movement.</p><p><strong>Conclusions: </strong>Integrating multimodal behavioral indicators with AI-based modeling enables clinically meaningful differentiation between bipolar and unipolar depression.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic signatures of attention problems in youth with childhood exposure to family and community violence.","authors":"Renata Queiroz Ramos, Adriane Feijó Evangelista, Cosme Marcelo Furtado Passos da Silva, Fernanda Serpeloni, Joviana Quintes Avanci, Natasha Reis Lacerda, Simone Gonçalves de Assis","doi":"10.1111/pcn.70131","DOIUrl":"https://doi.org/10.1111/pcn.70131","url":null,"abstract":"<p><strong>Aim: </strong>The link between violence-related epigenetic changes and attentional problems (APs) is still not well understood. This article examines if exposure to family and community violence during childhood and adolescence may shape DNA methylation patterns associated with attention in youth.</p><p><strong>Method: </strong>This study used data from a longitudinal cohort with 500 first-grade Brazilian students. The following measures were investigated: attention problems, family violence, and community violence. Mann-Whitney-U and Kruskal-Wallis were used to identify group differences and Spearman correlation to access variables associations. Top 1% CpGs were overlapped. Epigenetics analyses were performed using Epigenome-wide association study (EWAS, 850K) and Prediction Analysis of Microarray (PAM). Linear regression models were applied to candidate genes analyses. All models used significance level at 5%.</p><p><strong>Results: </strong>AP was correlated to three types of violence (family, psychological family, and community violence). EWAS and PAM identified five genes in common: SLC43A2, SMN1/2, TPO, DTNA, and CLMN, collectively implicating neurodevelopmental, cellular homeostatic, and endocrine mechanisms. PAM successfully predicted attention problems (AP) in two models (AP alone and AP combined with physical violence). Among the selected genes, several were related to neurodevelopment and neuronal maintenance (SMN1/2, MYT1L); structural organization (DTNA, CLMN); and cellular signaling (DTNA) functions; and immune, metabolic, and endocrine responses (SLC43A2, TPO). These alterations were associated with attention problems and exposure to family and community violence.</p><p><strong>Conclusion: </strong>Early-life violence is biologically embedded through epigenetic modifications affecting attention, pointing to a complex interplay between environmental adversity and gene regulation. Integrative prevention strategies targeting psychosocial/molecular pathways of vulnerability are needed.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insula-cerebellar functional connectivity associated with somatic symptoms in mood disorders: Differential patterns and longitudinal evidence in major depressive disorder.","authors":"Shin Hattori, Toshiharu Kamishikiryo, Alan S R Fermin, Yoichiro Matsumoto, Yuki Mitsuyama, Eri Itai, Yoshikazu Masuda, Go Okada","doi":"10.1111/pcn.70132","DOIUrl":"https://doi.org/10.1111/pcn.70132","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to identify the resting-state functional connectivity (rsFC) of insula subregions associated with nonspecific somatic symptoms in mood disorders and to examine whether these connections are state-dependent.</p><p><strong>Methods: </strong>In Phase 1, seed-based rsFC analyses were performed using 12 insula subregions from the Brainnetome Atlas in patients with major depressive disorder (MDD), bipolar disorder (BD), and healthy controls. Associations between rsFC and the somatic factor of the Beck Depression Inventory-II (BDI_S) were examined in each group. In Phase 2, insula connections significantly associated with BDI_S in the MDD group were selected as regions of interest, and longitudinal changes in rsFC over 6 weeks were tested for associations with changes in BDI_S.</p><p><strong>Results: </strong>In Phase 1, rsFC between several insular subregions and the left cerebellar lobule VIII (Cereb 8_L) showed modest negative correlations with BDI_S in the MDD group, while rsFC involving the right superior lateral occipital cortex or Cereb 8_L showed positive correlations in the BD group. In MDD and BD, the rsFC between the right dorsal granular insula (dIg_R) and Cereb 8_L showed opposite relationships with BDI_S in the cross-sectional analysis. In Phase 2, increases in dIg_R-Cereb 8_L were significantly associated with reductions in BDI_S in MDD with a modest effect size.</p><p><strong>Conclusion: </strong>Insula-cerebellum rsFC, particularly between dIg_R and Cereb 8_L, may serve as a potential state-related neural correlate of nonspecific somatic symptoms in MDD, with potentially distinct functional roles in MDD versus BD.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive heterogeneity in major depressive disorder: Neuroimaging, transcriptomic, and neurotransmitter profiles.","authors":"Yushun Yan, Jia'ao Yu, Liang Zuo, Min Wang, Jinxue Wei, Yikai Dou, Xiao Yang, Xiaohong Ma","doi":"10.1111/pcn.70126","DOIUrl":"https://doi.org/10.1111/pcn.70126","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is often accompanied by cognitive impairment; however, the cognitive heterogeneity of MDD and its neurobiological context remain poorly understood.</p><p><strong>Methods: </strong>A total of 198 participants with MDD and 275 HCs underwent multi-domain cognitive assessments and multi-modal MRI acquisition. A semi-supervised approach was applied to identify cognitive dimensions of MDD, and individual-level structural-enriched functional networks (SFNs) were constructed. Network-based statistics were applied to characterize network-level associations between structural-functional coupling deviation and cognitive dimensions. Furthermore, the correlations between the spatial pattern of SFN deviation and meta-analytic neurocognitive terms, cortical transcriptome, and neurotransmitter density distribution maps were detected.</p><p><strong>Results: </strong>In the MDD group, 103 individuals were assigned to Cluster 1, presenting widespread cognitive impairments, whereas 95 were assigned to Cluster 2, presenting cognitive preservations. An abnormally enhanced SFN subnetwork (P_Perm = 0.042) was identified, which showed significant spatial correlation with meta-analytic neurocognitive maps (r = 0.181, P < 0.001). The SFN deviation pattern was spatially associated with 2458 genes enriched primarily in neuronal and synaptic function, and these genes also showed enrichment for pathways annotated to neurodegenerative diseases (P_FDR < 0.05). In addition, SFN deviation was spatially associated with three neurotransmitter maps, including N-methyl-D-aspartate receptor, cannabinoid type-1 receptor, and norepinephrine transporter (P_FDR = 0.028).</p><p><strong>Conclusions: </strong>The study provides a data-driven characterization of cognitive heterogeneity in MDD, identifying two cognitive dimensions spanning from relative preservation to widespread impairment. By integrating structural-functional coupling deviations with transcriptomic and neurotransmitter maps, these findings provide preliminary biological context for interpreting cognitive heterogeneity in MDD.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional network reorganization and thalamocortical gating as neurobiological markers of recovery in somatic symptom disorder: A 6-month longitudinal source EEG study.","authors":"Yuna Jang, EKyong Yoon, Arum Hong, Hye Youn Park","doi":"10.1111/pcn.70127","DOIUrl":"https://doi.org/10.1111/pcn.70127","url":null,"abstract":"<p><strong>Aim: </strong>Somatic symptom disorder (SSD) is a functional disorder characterized by dysregulated neural processing of bodily signals. However, the neural mechanisms underlying recovery versus chronicity in SSD remain unclear. We investigated hierarchical neurophysiological features associated with symptom persistence and improvement using longitudinal source-localized electroencephalography (EEG).</p><p><strong>Methods: </strong>Resting-state EEG was analyzed in 83 patients with SSD and 80 matched healthy controls, with 76 participants completing a 6-month follow-up. We examined longitudinal changes in source-localized spectral power and network efficiency in relation to somatic and affective symptom trajectories.</p><p><strong>Results: </strong>Patients showed a significant reduction in somatic symptoms (P < 0.001) over time. SSD featured a persistent deficit in Gamma-band global efficiency (P = 0.035) that remained lower than healthy levels (P = 0.972 for interaction), representing residual neurobiological vulnerability. Conversely, thalamic spectral power exhibited significant group × time interactions (P < 0.05), reflecting longitudinal subcortical changes. Symptomatic relief was specifically associated with nodal efficiency reorganization within the left central sensorimotor region (Beta band, r = -0.54, P < 0.001). These associations remained robust after controlling for depression and anxiety, with mediation analyses indicating that these associations were largely independent of affective fluctuations.</p><p><strong>Conclusions: </strong>SSD involves a multilayered neurobiological architecture, where persistent network-level limitations coexist with longitudinal subcortical and cortical changes. While broader functional deficits endure, clinical recovery is accompanied by longitudinal thalamic changes and is more directly associated with localized sensorimotor reorganization. These findings suggest that addressing both persistent network differences and longitudinal recovery-related changes is essential for effective SSD management.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoupling of amygdala-salience circuit associated with negative symptoms in adolescents with early-onset schizophrenia.","authors":"Manqi Zhang, Yani Zheng, Jinqiang Zhang, Zhening Liu, Fu Liu, Zhifeng Tian, Jiaqi Ouyang, Xue Wen, Weidan Pu","doi":"10.1111/pcn.70080","DOIUrl":"10.1111/pcn.70080","url":null,"abstract":"<p><strong>Aim: </strong>Early-onset schizophrenia (EOS) is characterized by prominent negative symptoms, particularly socio-emotional deficits. This study examined functional connectivity within the large-scale socio-emotional circuits, including negative affect, positive affect, and salience circuits, and their associations with negative symptoms in EOS adolescents.</p><p><strong>Method: </strong>A total of 106 adolescents with EOS and 67 healthy controls (HCs) underwent resting-state fMRI and clinical assessment using the Positive and Negative Syndrome Scale (PANSS). Seed-based functional connectivity analyses were performed focusing on key nodes within affect circuits and the salience network, including the amygdala, caudate, medial frontal cortex, orbitofrontal cortex, anterior cingulate cortex, insular cortex, pallidum, putamen, and nucleus accumbens. Associations between altered connectivity and negative symptom dimensions were further examined.</p><p><strong>Results: </strong>Compared with HCs, EOS patients demonstrated significantly decreased functional connectivity between the amygdala and core salience network regions, reflecting a decoupling of this circuit, including the bilateral insula, anterior cingulate cortex, and putamen. Reduced amygdala-salience connectivity was significantly associated with poor rapport. Similar patterns of amygdala-salience decoupling were observed in both drug-naïve and medicated patients, although medicated patients showed more spatially restricted decoupling involving the right amygdala-right putamen connection.</p><p><strong>Conclusions: </strong>These findings indicate disrupted coupling between the amygdala and the salience circuit in adolescents with EOS, which may contribute to socio-emotional dysfunction and negative symptoms. The persistence of amygdala-salience decoupling across both drug-naïve and medicated EOS patients suggests that this circuit abnormality is not fully normalized by current antipsychotic treatment and may represent a candidate target for future mechanistic and longitudinal studies.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"748-756"},"PeriodicalIF":5.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and tolerance of oral ketamine: A systematic review.","authors":"Nathalia Novaretti, Rebeca Mendes P Pessoa, Jaime Eduardo Cecílio Hallak, Rafael Guimarães Dos Santos, Marcos Hortes N Chagas","doi":"10.1111/pcn.70091","DOIUrl":"10.1111/pcn.70091","url":null,"abstract":"<p><p>Oral ketamine has gained increasing interest beyond anesthesia, particularly for treatment-resistant depression, chronic pain, and pediatric procedural sedation. Despite expanding off-label use, there is no standardized pharmaceutical formulation, and long-term safety remains uncertain. A synthesis of evidence on safety and tolerability of the oral route is therefore needed to inform clinical practice and regulatory development. This systematic review evaluated the safety and tolerability profile of oral ketamine in humans and characterized dosing strategies across randomized controlled trials. A systematic search was conducted in PubMed, Embase, Scopus, and Web of Science from inception to November 2025 (PROSPERO CRD420251065295). Randomized placebo-controlled trials evaluating oral (es)ketamine in any clinical population were included. Primary outcomes were safety and tolerability. Risk of bias was assessed using the RoB2 tool, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Eighteen trials were included, comprising adults, children, and healthy volunteers. In depression studies (n = 5; 427 participants), adverse effects were predominantly mild and transient. Pediatric premedication trials (n = 239) reported transient neurological effects without clinically significant safety concerns. Pain and experimental studies (n = 372) showed mostly mild adverse events, with dissociative symptoms at higher doses. Comparative analyses indicated higher rates of dizziness, sedation, and dissociative symptoms with ketamine, while serious adverse events were rare. Overall, oral ketamine demonstrates a favorable short-term safety profile. However, the certainty of evidence is low, and long-term safety remains uncertain.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"730-739"},"PeriodicalIF":5.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to 'Hypnotic discontinuation is not synonymous with successful deprescribing: A Taiwan perspective'.","authors":"Kazuhiro Kurihara, Ko Sugiura, Akiyoshi Shimura, Kentaro Matsui, Shunsuke Takagi, Yuichi Inoue, Yoshikazu Takaesu","doi":"10.1111/pcn.70130","DOIUrl":"https://doi.org/10.1111/pcn.70130","url":null,"abstract":"<p><p>This article is a response to 'Hypnotic discontinuation is not synonymous with successful deprescribing: A Taiwan perspective'.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative methylation and miRNA dysregulation in dlPFC reveal distinct molecular signatures of suicide and non-suicide subtypes in major depressive disorder.","authors":"Aleena Francis, Yogesh Dwivedi","doi":"10.1111/pcn.70090","DOIUrl":"10.1111/pcn.70090","url":null,"abstract":"<p><strong>Aim: </strong>Major depressive disorder (MDD) is a leading cause of disability and carries a high risk of suicide. MicroRNAs (miRNAs) are epigenetic regulators implicated in MDD and can be regulated by DNA methylation, potentially reshaping downstream gene networks. We investigated methylation-linked miRNA dysregulation and explored whether these changes are specifically associated with suicide among MDD patients.</p><p><strong>Methods: </strong>Genome-wide DNA methylation profiling of the dorsolateral prefrontal cortex from 15 MDD patients who died by suicide (MDD+S), 17 MDD patients who died from causes other than suicide (MDD-S), and 16 controls (C) using the Illumina 850K MethylationEPIC array was integrated with small RNA sequencing-based miRNA quantification to identify miRNA-associated differentially methylated probes (DMPs), link methylation to miRNA expression, and infer downstream targets and pathways.</p><p><strong>Results: </strong>Differential methylation analysis (P ≤ 0.05) revealed 139 miRNA-linked DMPs in C vs. MDD+/-S, 135 in C vs. MDD-S, 179 in C vs. MDD+S, and the highest in MDD+S vs. MDD-S (235). CpG-miRNA pairing (within 1500kb promoter) followed by Spearman correlation identified inverse associations between CpG β values and miRNA expression, with the most consistent signals in suicide-status-stratified subsets, including cg06341821-hsa-miR-574-3p and cg25451306-hsa-miR-2110 in MDD+S-related contrasts, and cg06179179-hsa-miR-595 in MDD-S-related contrasts. High-confidence target prediction and ClueGO enrichment indicated distinct biology: miR-595 target genes in MDD-S were enriched for interferon/innate immune signaling, whereas miR-2110 target genes in MDD+S were enriched for ligand-gated ion channel activity and synaptic/receptor signaling.</p><p><strong>Conclusion: </strong>This integrated approach identifies methylation-regulated miRNA pathways that may play key roles in the molecular pathogenesis of MDD and suicide.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"757-764"},"PeriodicalIF":5.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148056499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}