Molecular Psychiatry最新文献

{"title":"Investigating the associations between neurodevelopmental and psychiatric genetic liability and adverse social and functional outcomes across childhood, adolescence and young-adulthood","authors":"Beatrice Fury, Charlotte Dennison, Lucy Riglin, Amy Shakeshaft","doi":"10.1038/s41380-026-03903-x","DOIUrl":"https://doi.org/10.1038/s41380-026-03903-x","url":null,"abstract":"Neurodevelopmental and psychiatric conditions often originate in youth and can lead to adverse social and functional outcomes. It is unclear whether these associations are driven by genetic liability to these conditions, with possible developmental differences. We examined multivariable associations between polygenic scores (PGS) for attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), schizophrenia, bipolar disorder, depression, anxiety and three outcomes: peer problems, educational attainment/employment and suicidality, in childhood, adolescence and young-adulthood. Data were analysed from the Avon Longitudinal Study of Parents and Children; outcomes at ages 10–13, 16 and 24–25 years. ADHD PGS was associated with peer problems (OR = 1.13, p = 0.020; OR = 1.21, p < 0.0001; OR = 1.14, p = 0.010) and lower educational attainment/employment in childhood, adolescence and young-adulthood(OR = 1.40, p < 0.0001; OR = 1.62, p < 0.0001; OR = 1.29, p = 0.005 respectively) and suicidality in childhood (OR = 1.13, p = 0.030). ASD PGS was associated with peer problems and suicidality in childhood (OR = 1.24, p < 0.0001; OR = 1.24, p = <0.0001) and greater educational attainment in childhood and adolescence (OR = 0.88, p = 0.004; OR = 0.77, p = 0.007). Depression PGS was associated with peer problems in childhood and young-adulthood (OR = 1.18, p = 0.003; OR = 1.21, p < 0.0001), and poorer educational attainment/employment and suicidality in adolescence (OR = 1.39, p = 0.004; OR = 1.28, p < 0.0001) and young-adulthood (OR = 1.26, p = 0.017; OR = 1.42, p < 0.0001). We did not find strong evidence of associations for schizophrenia, bipolar disorder or anxiety PGS. These findings suggest that genetic liability to neurodevelopmental and psychiatric conditions are associated with a range of social/functional outcomes, although the strength and direction of association vary by PGS, outcome and development stage. This highlights the importance of examining genetic liability to multiple conditions simultaneously and of a developmental perspective.","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"18 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATF4 Modulates Group 1 mGluR-Dependent molecular signaling, hippocampal plasticity and behavior","authors":"Shiyu Wang, Yeeun Yook, Simon Lizarazo, Kwan Young Lee, Kevin Van Bortle, Justin S. Rhodes, Catherine A. Christian-Hinman, Nien-Pei Tsai","doi":"10.1038/s41380-026-03919-3","DOIUrl":"https://doi.org/10.1038/s41380-026-03919-3","url":null,"abstract":"Group 1 metabotropic glutamate receptors (Gp1 mGluRs) are critical effectors in behavior. Abnormal Gp1 mGluR signaling is frequently observed in neurodevelopmental and cognitive disorders. It is established that activation of Gp1 mGluR elicits translation-dependent neuronal plasticity mechanisms, such as long-term synaptic depression (LTD). However, whether and how transcription is involved is not clear. In this study, we study a cellular stress associated transcription factor, activation transcription factor 4 (ATF4). We first employed RNA sequencing and revealed that knocking down ATF4 using ATF4 heterozygous mice upregulates or downregulates multiple genes with known functions in translational control or synaptic plasticity in a sex-dependent manner. When searching for a crosstalk between ATF4 and known synaptic plasticity mechanisms, we found that activation of Gp1 mGluR promotes the expression and nuclear distribution of ATF4. Using ATF4 heterozygous mice, we further confirmed that ATF4 is required for Gp1 mGluR-induced activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), de novo translation and hippocampal LTD at Schaffer-collateral synapses. When assessing animal behavior, our results indicated that knocking down ATF4 impairs learning behavior and precludes mGluR-dependent reduction in repetitive behavior only in female mice. Altogether, our study suggests ATF4 as an activity-dependent transcription factor required for Gp1 mGluR-dependent translation, hippocampal LTD, and behavior.","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"72 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double-blind, randomized clinical trial targeting theta oscillations with transcranial alternating current stimulation (tACS) for cognitive control in male methamphetamine patients.","authors":"Yang Tian, Linjun Jiang, Xianchen Gang, Meng Chen, Shanshan Tang, Xiaotao Wang, Xiangyang Zhang, Dongmei Wang","doi":"10.1038/s41380-026-03900-0","DOIUrl":"https://doi.org/10.1038/s41380-026-03900-0","url":null,"abstract":"<p><p>Methamphetamine use disorder is associated with significant cognitive control deficits, and effective treatments remain limited. Frontal midline theta (FM-theta) oscillations are implicated in cognitive control, but whether theta-frequency transcranial alternating current stimulation (theta-tACS) can improve proactive and reactive control in this population remains unclear. This study initially enrolled 68 male participants diagnosed with methamphetamine use disorder according to DSM-5 criteria. Among them, 56 individuals completed all study procedures and were included in the final analysis. Cognitive control was assessed using a conditional stop-signal task with concurrent EEG recording. The stimulation protocol comprised 15 consecutive daily sessions, during which participants received either active theta-tACS or sham stimulation (2 mA, FCz - Pz montage) in a double-blind design. Following the 15-day theta-tACS stimulation, patients exhibited a significant improvement in preparation cost (p = 0.001) and an increased inhibition rate (p = 0.003). EEG analyses showed that tACS selectively enhanced late-stage proactive control-related theta power (p = 0.026), without significantly modulating theta activity associated with reactive control (p > 0.05). Importantly, the tACS stimulation restored the functional coupling between FM-theta activity and proactive control performance (p = 0.04), and baseline late-stage theta power at T0 positively predicted improvement in preparation cost (ΔT1 - T0) during proactive control (p = 0.01). Finally, a mediation analysis revealed that the tACS-induced improvement in inhibition rate was mediated by the enhanced preparation cost. These findings suggested theta-tACS enhances proactive control by restoring the functional coupling between FM-theta activity and proactive control, which in turn triggers a cascading improvement in reactive control.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network adaptability governs resilience and susceptibility to social defeat.","authors":"Sarah Ayash, Stefan Paul Koch, Jeehye An, Ulrich Schmitt, Susanne Mueller, Marco Foddis, Esin Candemir, Oliver Tüscher, Philipp Boehm-Sturm, Marianne B Müller","doi":"10.1038/s41380-026-03899-4","DOIUrl":"https://doi.org/10.1038/s41380-026-03899-4","url":null,"abstract":"<p><p>Stress resilience-the ability to maintain mental health after adversity-manifests in humans and rodents as efficient threat-safety discrimination and fear extinction. Although behavioral differences between resilient and susceptible individuals are well documented, the brain-wide structural signatures that distinguish resilience, susceptibility, and impaired threat learning remain poorly defined. Using a translational mouse model of chronic social defeat stress in male C57BL/6 J mice (n = 55), combined with preregistered multimodal magnetic resonance imaging with graph-theoretical analyses, we identify structural and network-level correlates of three behavioral phenotypes. Resilient animals exhibited greater microstructural complexity in prefrontal regions, and showed signatures consistent with enhanced inhibitory gating within amygdalar circuits. In contrast, susceptible animals-defined behaviorally by fear generalization and resistance to extinction-exhibited dentate gyrus alterations across all measures, suggesting diminished microstructural adaptability. A third phenotype, impaired threat learning-mice that failed to avoid individuals from a threatening strain-was associated with altered CA1/CA2 microstructure and reduced structural connectivity in pons, pointing to disrupted hippocampal-brainstem interactions during memory consolidation. These findings demonstrate that resilience, susceptibility, and impaired threat learning arise from dissociable patterns of brain organization, with resilience reflecting adaptive circuit-level organization and susceptibility and impaired threat learning exhibiting distinct forms of microstructural and network reorganization.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium chloride in vitro treatment shows potential to rescue the neuronal phenotype caused by WDFY3 haploinsufficiency","authors":"Moritz J. Paha,Arshi Mustafa,Lyvin Tat,Sandy Richter,Linnaeus Bundalian,Sworadip Chowdhury,Akhil Velluva,Robin-Tobias Jauss,Knut Krohn,Kathleen Schön,Max Holzer,Anna S. Kirstein,Meena Balasubramanian,María Juliana Ballesta-Martínez,Lynne M. Bird,Kirsty Bradshaw,Ange-Line Bruel,Alfredo Brusco,Yanmin Chen,Aurore Garde,Silvia Guarducci,Yoel Gofin,Rachel E. Harrison,Alexis Heidlebaugh,Anna Hurst,Julian A. Martinez-Agosto,Jessica L. Mester,Alistair T. Pagnamenta,Marilena Pantaleo,Andrea Paras,Angela Peron,Tiziana Pisano,Ahna M. Rabani,Marcello Scala,Elena Shukarova-Angelovska,Sui Yang,Slavica Trajkova,Sheila Umayam,Tianyun Wang,Rami Abou Jamra,Johannes R. Lemke,Wieland Kiess,Konstantinos S. Zarbalis,Antje Garten,Diana Le Duc","doi":"10.1038/s41380-026-03844-5","DOIUrl":"https://doi.org/10.1038/s41380-026-03844-5","url":null,"abstract":"Abstract We provide a comprehensive phenotypic characterization of loss-of-function (LoF) variants in WDFY3 based on the largest cohort reported to date ( n  = 32). Our findings define a monogenic disorder marked by neuropsychiatric features (including autism and ADHD), mild to moderate neurodevelopmental delay, and variable brain growth – most commonly macrocephaly and in one case reduced head circumference. To investigate the effect of WDFY3 LoF we performed knockdown (KD) in the human neuroblastoma cell line SH-SY5Y and used a Wdfy3 -haploinsufficient mouse model. WDFY3 KD impaired clearance of protein aggregates and decreased protein levels of the ubiquitin-binding protein p62. Transcriptomic analyses identified dysregulation in gene networks that are primarily involved in nervous system development, neuron projection, MAPK/ERK1/2, and WNT/β-catenin signaling. This was confirmed at protein level. Neuronal cell proliferation was increased, as evidenced by elevated cell counts and proliferation markers Ki-67 and PCNA . Conversely, neuronal cell differentiation was impaired, as indicated by reduced neurite outgrowth. We show that β-catenin is downregulated, while GSK3B is upregulated. LiCl activates WNT/β-catenin signaling by inhibiting GSK3B. We thus tested LiCl treatment, which significantly increased WDFY3 expression. Moreover, in vitro treatment improved the neurite branching capacity of Wdfy3 -haploinsufficient neurons above the level of the wild type, although this specific effect appeared independent of WNT/β-catenin signaling. In sum, we expand on the phenotype related to WDFY3 LoF and provide insights into the pathophysiology using in vitro human and murine neuronal models. Our findings suggest that LiCl may serve as a potential therapeutic strategy for patients with WDFY3 LoF variants.","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"7 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Read sequencing in psychiatric omics: a systematic review of current evidence","authors":"Bruno Takao Real Karia,Vanessa Ota,Renato Polimanti,Marcos Leite Santoro,Sintia Belangero,Carolina Muniz Carvalho","doi":"10.1038/s41380-026-03909-5","DOIUrl":"https://doi.org/10.1038/s41380-026-03909-5","url":null,"abstract":"Abstract Background The comprehensive elucidation of genomic relevance for mental disorder was, until recently, constrained by the limitations of microarrays or short-read sequencing (SRS). Long-read sequencing (LRS) provides access to complex classes of genetic variation and genomic architecture that are largely obscured in SRS approaches, making it a powerful tool for uncovering missing heritability and mechanistic insights in mental disorders. Objective We synthesize current evidence on the application of LRS technologies across genomic, transcriptomic, and methylomic studies of mental disorders. The systematic review was conducted in accordance with PRISMA guidelines. Results and discussion The literature search yielded 2,166 articles, and 14 were included in the review after applying inclusion and exclusion criteria. From a genomic perspective, LRS consistently outperformed SRS, increasing structural variant (SV) and de novo mutation (DNM) detection, particularly resolving medium-sized SVs and large inversions in repetitive regions. Transcriptomic studies established LRS as essential for achieving full-length transcript resolution, uncovering substantial novel isoform diversity and widespread alternative splicing events in the human neocortex. Crucially, LRS demonstrated that psychiatric risk is often conferred by dysregulated alternative splicing leading to isoform-specific imbalances, rather than altered total gene expression. At the epigenomic level, LRS enabled the haplotype-specific mapping of Allele-Specific Methylation within genome-wide significant loci, linking genetic risk to epigenetic dysregulation. Overall, LRS represents a significant technological advancement, providing the high-resolution molecular detail necessary to begin characterizing the complex relationships between genetic variation, splicing dynamics, and epigenetic modifications, thereby helping to contextualize psychiatric risk associations for future translational research.","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"52 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosing autoimmune encephalitis in psychiatry: clinical recommendations and unresolved challenges from the GENERATE network.","authors":"Dominique Endres, Katharina von Zedtwitz, Ludger Tebartz van Elst, Katharina Domschke, Judith Weiser, Arnim J Gaebler, Thomas Frodl, Elias Wagner, Iris Jäger, Alkomiet Hasan, Josef Priller, Cora Schefft, Paul J Wirsching, Sibylle Haußleiter, Georg Juckel, Philipp Müller, David H V Vogel, Alexandra Philipsen, Timo J Faustmann, Daniel Kamp, Leonhard Schilbach, Dag Scherfeld, Milenko Kujovic, Eva Meisenzahl, Stefanie Fischer, Jonathan Repple, Udo Dannlowski, Niels Hansen, Karl Bechter, Oliver Tüscher, Heiko Paland, Daniel Luedecke, Hannah B Maier, Margarete Mattern, Michael Kluge, Alexandra Neyazi, Johann Steiner, Sebastian Walther, Ilya Ayzenberg, Manuel A Friese, Tania Kümpfel, Sven G Meuth, Kevin Rostasy, Simone C Tauber, Franziska S Thaler, Klaus-Peter Wandinger, Brigitte Wildemann, Carsten Finke, Jan Lewerenz, Christian Geis, Nico Melzer, Harald Prüss, Frank Leypoldt","doi":"10.1038/s41380-026-03871-2","DOIUrl":"https://doi.org/10.1038/s41380-026-03871-2","url":null,"abstract":"<p><p>Psychiatric syndromes can be caused by underlying autoimmune encephalitis (AE). This represents a diagnostic challenge at the interface of psychiatry and neurology. While AE mostly manifests with a combined, complex neuropsychiatric syndrome, some patients with AE may (initially) present with predominant or isolated psychiatric symptoms. These cases can be difficult to classify, and diagnostic approaches vary considerably across clinical settings. This paper from the GErman NEtwork for Research on AuToimmune Encephalitis (GENERATE) provides interdisciplinary expert recommendations from psychiatry and neurology for the diagnostic evaluation of patients with suspected AE as the cause of psychiatric syndromes for psychiatric care settings. It integrates current scientific evidence with practical, empirical considerations from routine clinical care in different healthcare settings. The proposed diagnostic approach to detect psychiatric manifestations of AE emphasizes a rational, stepwise evaluation incorporating clinical assessment, magnetic resonance imaging, electroencephalography, blood testing, cerebrospinal fluid (CSF) analysis, and neuronal/glial antibody testing in serum and CSF. In diagnostically ambiguous individuals, [¹⁸F]fluorodeoxyglucose positron-emission-tomography and advanced antibody testing (e.g., live-cell-based assays) or neuroimaging techniques (e.g., volumetric analysis) may provide additional supportive information. Typical findings and limitations of diagnostic modalities are discussed to facilitate appropriate interpretation and to avoid under-recognition or overdiagnosis. Importantly, these recommendations do not aim to define new disease entities or diagnostic criteria, but rather to support a harmonized and pragmatic diagnostic approach to patients presenting with psychiatric syndromes suspected to be caused by underlying AE. Finally, key unresolved issues in this evolving field of immunopsychiatry are outlined, and promising research strategies are described.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted PQBP1-HNRNPU-LINE-1 axis underlies aberrant neurodevelopment in renpenning syndrome.","authors":"Jinyu Zhang, Wenzheng Qu, Xuejun Cheng, Lan Li, Ying Li, Shilong Li, Lei Ye, Lin Yu, Yun Li, Peifang Jiang, Xiling Jiang, Jun Xu, Chaochun Zou, Qiang Shu, Xuekun Li","doi":"10.1038/s41380-026-03908-6","DOIUrl":"https://doi.org/10.1038/s41380-026-03908-6","url":null,"abstract":"<p><p>Mutations in RNA splicing factor PQBP1 cause Renpenning syndrome (RS), yet whether LINE-1 (L1) contributes to RS pathogenesis remains unclear. Here, we generated human forebrain organoids model carrying a novel patient-derived PQBP1 variant (c.28 C > G; p.R10G), and observed impaired neurogenesis in RS organoids. Bulk and single-cell RNA-sequencing revealed that PQBP1 R10G mutation upregulated evolutionarily ancient L1 expression and induced aberrant L1 splicing, resulting in the redundant production of non-canonical L1-containing transcripts. Mechanistically, disrupted PQBP1-HNRNPU interaction by PQBP1 R10G mutation impaired U1/U2 small nuclear ribonucleoprotein (snRNP) recruitment to splicing sites, leading to increased L1-containing intron retention of neurodevelopmental genes, including WDR11. L1 retention reduced canonical WDR11 transcripts and consequently protein expression. Canonical WDR11, not L1-containing isoform, ameliorated the neurodevelopmental deficits of RS organoids. Together, our findings establish the dysregulated PQBP1-HNRNPU-L1 axis as a pathogenic driver of RS and nominate WDR11 as a potential therapeutic target for RS.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics characterization of chronic social defeat stress recall-activated nuclei in Arc-GFP mice.","authors":"Monika Chanu Chongtham, Dewi Hartwich, Hristo Todorov, Nicolas Ruffini, Eva Weis, Matthias Linke, Susann Schweiger, Ulrich Zechner, Johannes Gräff, Beat Lutz, Susanne Gerber, Jennifer Winter","doi":"10.1038/s41380-026-03834-7","DOIUrl":"https://doi.org/10.1038/s41380-026-03834-7","url":null,"abstract":"<p><p>Susceptibility to chronic social stressors often results in the development of mental health disorders including major depressive and anxiety disorders. In contrast, some individuals remain resilient even after repeated stress exposure. Understanding the molecular drivers underlying these divergent phenotypic outcomes is crucial. However, previous studies using the chronic social defeat (CSD) stress model have been limited by the use of bulk tissues investigating single omics domains. To overcome these limitations, here, we applied the CSD mouse model to Arc-GFP mice for investigating the mechanistic divergence between susceptibility and resilience, specifically in stress recall-activated nuclei. By conducting an in-depth analysis of the less-known differential methylome landscape in the ventral hippocampus, we noted unique phenotype-specific alterations in multiple biological processes with an overrepresentation of GTPase-related mechanisms. Interestingly, the differentially methylated regions were enriched in ETS transcription factor binding sites (TFBSs), important targets of the Ras-ETS signaling pathway. This differential methylation in the ETS TFBSs could form the basis of persisting stress effects long after stressor exposure. Furthermore, by integrating the methylome modifications with transcriptomic alterations, we delineated the GTPase-related mechanisms differentially activated in the resilient and susceptible phenotypes with alterations in endocytosis overrepresented in the susceptible phenotype. Overall, our findings reveal novel insights underlying the resilience-susceptibility divergence.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postnatal distress, neonatal cerebellar myelination and neurodevelopmental outcomes at 18 months","authors":"Alissa Papadopoulos,Emily S. Nichols,Emma G. Duerden","doi":"10.1038/s41380-026-03902-y","DOIUrl":"https://doi.org/10.1038/s41380-026-03902-y","url":null,"abstract":"","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"1 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}