Biological psychiatry global open science最新文献

{"title":"Moving Toward Neurobiological, Multidomain, and Contextually Grounded Models of Resilience","authors":"Manpreet K. Singh","doi":"10.1016/j.bpsgos.2025.100603","DOIUrl":"10.1016/j.bpsgos.2025.100603","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100603"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in High-Frequency Connectivity Among Large-Scale Functional Networks Linked to Major Depressive Disorder and Treatment-Resistant Depression","authors":"Ty Lees ,&nbsp;Sarah E. Woronko ,&nbsp;Mohan Li ,&nbsp;Jason N. Scott Jr. ,&nbsp;Manuel Kuhn ,&nbsp;Shiba M. Esfand ,&nbsp;Mario Bogdanov ,&nbsp;Brian W. Boyle ,&nbsp;Samantha R. Linton ,&nbsp;Lauren R. Borchers ,&nbsp;Peter Zhukovsky ,&nbsp;Courtney Miller ,&nbsp;Paula Bolton ,&nbsp;Shuang Li ,&nbsp;Robert C. Meisner ,&nbsp;Diego A. Pizzagalli","doi":"10.1016/j.bpsgos.2025.100602","DOIUrl":"10.1016/j.bpsgos.2025.100602","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) and treatment-resistant depression (TRD) have each been characterized by altered neural connectivity largely associated with the triple model of the default mode (DMN), frontoparietal (FPN), and salience (SN) networks. However, the direction (i.e., hyper- vs. hypoconnectivity) and the specificity (i.e., depression broadly vs. TRD) of these alterations remains unclear. Thus, in the current study, we compared high-frequency between- and within-network resting-state functional connectivity (rsFC) in healthy control (HC) individuals, individuals with MDD, and individuals with TRD.</div></div><div><h3>Methods</h3><div>Ninety-six channel resting-state electroencephalogram data were collected from 34 participants with MDD (22 women, mean ± SD age: 29.92 ± 9.57 years), 24 participants with TRD (16 women, age: 44.35 ± 15.86 years), and 34 HC participants (25 women, age: 32.49 ± 14.07 years). Based on previous findings, exact low-resolution electromagnetic tomography was used to estimate theta and beta rsFC within and between the DMN, FPN, and SN.</div></div><div><h3>Results</h3><div>Participants with depression (i.e., pooled MDD and TRD participants) had enhanced within-DMN beta1 (12.5–18 Hz) connectivity compared with controls. Compared with MDD participants, participants with TRD showed increased within-DMN, DMN to FPN, and FPN to SN beta3 (21.5–30 Hz) connectivity. These effects persisted when controlling for current depressive symptoms.</div></div><div><h3>Conclusions</h3><div>Differences in high-frequency rsFC, particularly in the beta bands, among the DMN, FPN, and SN may partially account for neural mechanisms of treatment resistance. However, future work probing the heterogeneity (e.g., medication status, age of onset, lifetime episode count) and time course (e.g., length and frequency of episodes) of depression is needed to increase our understanding of these changes in neural connectivity.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100602"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of a DDX3X Gene Supplementation Therapy Including Expanded Characterization and Novel Findings of Sleep Disturbances in Ddx3x Haploinsufficient Mice","authors":"Andrea Boitnott ,&nbsp;Anjala Jiji ,&nbsp;Erik J. Plautz ,&nbsp;Yuhui Hu ,&nbsp;Xin Chen ,&nbsp;Steven J. Gray","doi":"10.1016/j.bpsgos.2025.100599","DOIUrl":"10.1016/j.bpsgos.2025.100599","url":null,"abstract":"<div><h3>Background</h3><div>DDX3X syndrome is a neurodevelopmental disorder caused by mutations in the <em>DDX3X</em> gene. It is one of many rare diseases for which there is no adequate treatment, but it has characteristics that make it potentially amenable to gene supplementation therapy.</div></div><div><h3>Methods</h3><div>An AAV9 (adeno-associated virus serotype 9)-mediated gene supplementation therapy was designed and tested for efficacy and safety in a mouse model of DDX3X syndrome. A total of 182 female <em>Ddx3x</em>^{<em>+/−</em>} mutant and <em>Ddx3x</em>^{<em>flox/+</em>} control littermates were dosed at postnatal day 1 with AAV9/DDX3X or vehicle and assessed throughout development for phenotypic benefit. To expand the readouts, sleep—a behavior disrupted in patients—was assessed by wireless telemetry.</div></div><div><h3>Results</h3><div>There was no effect of treatment on early postnatal developmental milestones. At 3 months, a dose-dependent amelioration in anxiety-like behavior was observed in treated <em>Ddx3x</em>^{<em>+/−</em>} mice, and a dose-dependent worsening in anxiety-like behavior was observed in treated <em>Ddx3x</em>^{<em>flox/+</em>} control mice. These treatment effects were not sustained at 12 months and were absent in mice that had not been subjected to prior developmental milestone testing. Significant sleep disturbances were observed in the <em>Ddx3x</em>^{<em>+/−</em>} mice at 4 months, but treatment had no effect on sleep.</div></div><div><h3>Conclusions</h3><div>While the gene therapy design used in this study was not effective, the data suggest that behavior can be modified by altering <em>Ddx3x</em> expression, warranting further exploration of gene therapy as a potential treatment approach. Additionally, the sleep disturbances present in <em>Ddx3x</em>^{<em>+/−</em>} mutant mice phenocopy the reduced sleep quality seen in patients, further validating this model for research.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100599"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Immunologic Underpinnings of Post-Stroke Depression","authors":"Nina Vindegaard Sørensen ,&nbsp;Anders Hougaard ,&nbsp;Christina Kruuse ,&nbsp;Michael Eriksen Benros","doi":"10.1016/j.bpsgos.2025.100575","DOIUrl":"10.1016/j.bpsgos.2025.100575","url":null,"abstract":"<div><div>Post-stroke depression is a common consequence of stroke with an estimated prevalence of approximately 30% in stroke patients. It negatively impacts both rehabilitation and quality of life after stroke. Stroke induces an acute activation of the immune system in the central nervous system with concomitant immunologic alterations in the periphery. Immunologic alterations have been associated with non-stroke-related depression, and the evidence points to both central and peripheral immune activation with bidirectional interactions. By identifying and evaluating the current evidence of immunologic alterations associated with depression, stroke, and post-stroke depression, we outline the current knowledge and hypotheses on stroke-related immunologic alterations and associations with the subsequent risk of post-stroke depression. This includes immune system alterations in the cerebrospinal fluid and blood; pre- and post-stroke infections; the blood-brain barrier; autoimmunity of the central nervous system; brain imaging; the spleen-brain, gut-brain, and neuroendocrine-immune axes; and immunogenetic studies. All these topics are discussed within the context of post-stroke depression, pointing to a potential involvement of a multifactorial immunologic pathophysiology. In this narrative review, we identify key directions for future research and conclude by offering perspectives related to the therapeutic potential and associated challenges of this underinvestigated but important topic in neuropsychiatry.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100575"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Comorbidities Among Psychiatric Disorders, Chronic Low Back Pain, and Spinal Degenerative Disease Using Observational and Genetically Informed Analyses","authors":"Dan Qiu ,&nbsp;Eleni Friligkou ,&nbsp;Jun He ,&nbsp;Brenda Cabrera-Mendoza ,&nbsp;Mihaela Aslan ,&nbsp;Mihir Gupta ,&nbsp;Renato Polimanti","doi":"10.1016/j.bpsgos.2025.100588","DOIUrl":"10.1016/j.bpsgos.2025.100588","url":null,"abstract":"<div><h3>Background</h3><div>Psychiatric disorders and symptoms are associated with differences in pain perception and sensitivity. These differences can have important implications in treating spinal degenerative disease (SDD) and chronic low back pain (CLBP).</div></div><div><h3>Methods</h3><div>Leveraging UK Biobank (UKB) (<em>n</em> = 402,072) and All of Us Research Program (AoU) (<em>n</em> = 157,415) data, we investigated the effects linking psychiatric disorders to SDD and CLBP. We applied multinominal regression models, polygenic risk scoring, and one-sample Mendelian randomization (MR) to triangulate the effects underlying the observed associations. We also performed gene ontology and drug-repurposing analyses to dissect the biology shared among mental illnesses, SDD, and CLBP.</div></div><div><h3>Results</h3><div>When we compared individuals affected only by SDD, those affected only by CLBP, and those affected by both conditions with control participants, observational and genetically informed analyses highlighted that the strongest effects across the 3 case groups were observed for alcohol use disorder, anxiety, depression, and posttraumatic stress disorder. Additionally, schizophrenia and its polygenic risk score appeared to have an inverse relationship with CLBP, SDD, and their comorbidity. One-sample MR highlighted a potential direct effect of internalizing disorders on the outcomes investigated that was particularly strong on SDD. Our drug repurposing analyses identified histone deacetylase inhibitors as targeting molecular pathways shared by psychiatric disorders, SDD, and CLBP.</div></div><div><h3>Conclusions</h3><div>These findings support that the comorbidity among psychiatric disorders, SDD, and CLBP is due to the contribution of direct effects and shared biology linking these health outcomes. These pleiotropic mechanisms, together with sociocultural factors, play a key role in shaping the SDD-CLBP comorbidity patterns that have been observed across the psychopathology spectrum.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100588"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Head Motion, Age, and Psychiatric Diagnoses in a Large-Scale Developmental Sample","authors":"Jonathan Power,&nbsp;Conor Liston","doi":"10.1016/j.bpsgos.2025.100569","DOIUrl":"10.1016/j.bpsgos.2025.100569","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100569"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Determinants of Health Influence Brain and Cognitive Function in Youth","authors":"Lucina Q. Uddin","doi":"10.1016/j.bpsgos.2025.100590","DOIUrl":"10.1016/j.bpsgos.2025.100590","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100590"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multimodal Observational Case-Control Study Exploring Gut Microbiota–Hippocampus Alterations in Individuals With High Positive Schizotypy From the General Population","authors":"Galya C. Iseli ,&nbsp;Jorge F. Vázquez-Castellanos ,&nbsp;David Coynel ,&nbsp;James M. Stone ,&nbsp;Mariana Zurita Soler ,&nbsp;Paul Allen ,&nbsp;Fernando Zelaya ,&nbsp;Muriel Derrien ,&nbsp;Undine E. Lang ,&nbsp;Martin Debbané ,&nbsp;Ulrich Ettinger ,&nbsp;Jeroen Raes ,&nbsp;André Schmidt","doi":"10.1016/j.bpsgos.2025.100567","DOIUrl":"10.1016/j.bpsgos.2025.100567","url":null,"abstract":"<div><h3>Background</h3><div>The hippocampus plays a critical role in psychosis, with reduced volume observed across the psychosis continuum. These structural changes are associated with cognitive deficits, symptom severity, and increased risk of psychosis progression. Elevated hippocampal perfusion and glutamate/GABA (gamma-aminobutyric acid) imbalance further suggest metabolic dysregulation as a key mechanism. Gut microbiota composition can influence hippocampal metabolism, but their interplay remains to be explored.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, we recruited 142 healthy participants from the general population, yielding 69 individuals with high schizotypy (HS) and 72 individuals with low schizotypy. All underwent clinical and cognitive testing, multimodal neuroimaging, and gut microbiota analysis via 16S ribosomal RNA gene sequencing. Hippocampal subfield volumes (structural magnetic resonance imaging), perfusion (arterial spin labeling) and glutamate/GABA levels (proton magnetic resonance spectroscopy), and microbial taxa (abundance, diversity, enterotypes) were assessed.</div></div><div><h3>Results</h3><div>Group comparisons of cognition, multimodal neuroimaging, and gut microbiome composition did not reveal significant differences after correction for multiple comparisons. Within the HS group, glutamate (<em>r</em> = 0.38, <em>p</em> = .003) and GABA (<em>r</em> = −0.36, <em>p</em> = .003) ratios were linked to social withdrawal. Across the entire sample, left hippocampal subfield volumes and glutamate/GABA levels differed significantly between predominant gut microbial enterotypes.</div></div><div><h3>Conclusions</h3><div>Our results suggest a potential relationship between aberrant gut microbial composition and hippocampal alterations in people with positive schizotypy from the general population. Our findings inform future large-scale research that further explores specific mechanisms of gut microbiome-hippocampus interactions in psychosis and the potential of tailored microbial interventions targeting hippocampal-mediated symptoms.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100567"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emerging Role of the DDAH Proteins in Psychiatric Disorders","authors":"Magdalini R. Vareltzoglou ,&nbsp;Roman N. Rodionov ,&nbsp;Anthony C. Vernon ,&nbsp;Nadine Bernhardt","doi":"10.1016/j.bpsgos.2025.100574","DOIUrl":"10.1016/j.bpsgos.2025.100574","url":null,"abstract":"<div><div>The heterogeneous nature of psychiatric disorders complicates their clinical management and the development of novel treatments, imposing a significant burden on both patients and health care systems. To address these challenges, it is essential to continuously identify new targets involved in their pathogenesis. In this narrative review, we propose the dimethylarginine dimethylaminohydrolase (DDAH) proteins, already known for their significant role in cardiovascular disease, as promising novel treatment targets for psychiatric conditions. The DDAH proteins exist in 2 isoforms, DDAH1 and DDAH2, which both regulate nitric oxide homeostasis. DDAH1 metabolizes the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA), while DDAH2 acts through ADMA-independent mechanisms. We synthesize current evidence from systemic studies, genetic analyses, postmortem brain samples, and animal models to evaluate the potential roles of DDAH proteins across psychiatric conditions. Most systemic studies have revealed increased peripheral ADMA levels across several psychiatric disorders, including schizophrenia, depression, bipolar disorder, substance use disorders, and attention-deficit/hyperactivity disorder. Alterations in ADMA levels are also observed in transdiagnostic clinical domains such as cognitive deficits, sleep disturbances, white matter hyperintensities, and oxidative stress. These ADMA changes are evident from early stages of illness and respond to current treatments, suggesting diagnostic potential. Genetic and postmortem brain data further link DDAH1 and DDAH2 to psychiatric symptomatology in patient populations. Finally, fundamental studies in model systems provide insights into their role in neural proliferation, differentiation, cell death, and oxidative stress regulation—key processes in the developing and the adult brain. These data support the view that DDAH proteins may play a role in the molecular mechanisms that underlie psychiatric disorders and merit more investigation as potential therapeutic candidates.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100574"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral MicroRNA Expression Patterns as Biomarkers for Adolescent Depression","authors":"Brunno Rocha Levone,&nbsp;Gerhard Schratt","doi":"10.1016/j.bpsgos.2025.100571","DOIUrl":"10.1016/j.bpsgos.2025.100571","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100571"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}