Biological Psychiatry最新文献

{"title":"Insomnia Subtypes Have Differentiating Deviations in Brain Structural Connectivity","authors":"Tom Bresser ,&nbsp;Tessa F. Blanken ,&nbsp;Siemon C. de Lange ,&nbsp;Jeanne Leerssen ,&nbsp;Jessica C. Foster-Dingley ,&nbsp;Oti Lakbila-Kamal ,&nbsp;Rick Wassing ,&nbsp;Jennifer R. Ramautar ,&nbsp;Diederick Stoffers ,&nbsp;Martijn P. van den Heuvel ,&nbsp;Eus J.W. Van Someren","doi":"10.1016/j.biopsych.2024.06.014","DOIUrl":"10.1016/j.biopsych.2024.06.014","url":null,"abstract":"<div><h3>Background</h3><div>Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within the insomnia population could obscure detection of involved brain circuits. In the current study, we investigated whether structural brain connectivity deviations differed between recently discovered and validated insomnia subtypes.</div></div><div><h3>Methods</h3><div>Structural and diffusion-weighted 3T magnetic resonance imaging data from 4 independent studies were harmonized. The sample consisted of 73 control participants without sleep complaints and 204 participants with insomnia who were grouped into 5 insomnia subtypes based on their fingerprint of mood and personality traits assessed with the Insomnia Type Questionnaire. Linear regression correcting for age and sex was used to evaluate group differences in structural connectivity strength, indicated by fractional anisotropy, streamline volume density, and mean diffusivity and evaluated within 3 different atlases.</div></div><div><h3>Results</h3><div>Insomnia subtypes showed differentiating profiles of deviating structural connectivity that were concentrated in different functional networks. Permutation testing against randomly drawn heterogeneous subsamples indicated significant specificity of deviation profiles in 4 of the 5 subtypes: highly distressed, moderately distressed reward sensitive, slightly distressed low reactive, and slightly distressed high reactive. Connectivity deviation profile significance ranged from <em>p</em> = .001 to <em>p</em> = .049 for different resolutions of brain parcellation and connectivity weight.</div></div><div><h3>Conclusions</h3><div>Our results provide an initial indication that different insomnia subtypes exhibit distinct profiles of deviations in structural brain connectivity. Subtyping insomnia may be essential for a better understanding of brain mechanisms that contribute to insomnia vulnerability.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 3","pages":"Pages 302-312"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional Structural-Functional Connectivity Coupling in Major Depressive Disorder Is Associated With Neurotransmitter and Genetic Profiles","authors":"Tongpeng Chu ,&nbsp;Xiaopeng Si ,&nbsp;Haizhu Xie ,&nbsp;Heng Ma ,&nbsp;Yinghong Shi ,&nbsp;Wei Yao ,&nbsp;Dong Xing ,&nbsp;Feng Zhao ,&nbsp;Fanghui Dong ,&nbsp;Qun Gai ,&nbsp;Kaili Che ,&nbsp;Yuting Guo ,&nbsp;Danni Chen ,&nbsp;Dong Ming ,&nbsp;Ning Mao","doi":"10.1016/j.biopsych.2024.08.022","DOIUrl":"10.1016/j.biopsych.2024.08.022","url":null,"abstract":"<div><h3>Background</h3><div>Abnormalities in structural-functional connectivity (SC-FC) coupling have been identified globally in patients with major depressive disorder (MDD). However, investigations have neglected the variability and hierarchical distribution of these abnormalities across different brain regions. Furthermore, the biological mechanisms that underlie regional SC-FC coupling patterns are not well understood.</div></div><div><h3>Methods</h3><div>We enrolled 182 patients with MDD and 157 healthy control participants and quantified the intergroup differences in regional SC-FC coupling. Extreme gradient boosting (XGBoost), support vector machine, and random forest models were constructed to assess the potential of SC-FC coupling as biomarkers for MDD diagnosis and symptom prediction. Then, we examined the link between changes in regional SC-FC coupling in patients with MDD, neurotransmitter distributions, and gene expression.</div></div><div><h3>Results</h3><div>We observed increased regional SC-FC coupling in the default mode network (<em>t</em>₃₃₇ = 3.233) and decreased coupling in the frontoparietal network (<em>t</em>₃₃₇ = −3.471) in patients with MDD compared with healthy control participants. XGBoost (area under the receiver operating characteristic curve = 0.853), support vector machine (area under the receiver operating characteristic curve = 0.832), and random forest (<em>p</em> &lt; .05) models exhibited good prediction performance. The alterations in regional SC-FC coupling in patients with MDD were correlated with the distributions of 4 neurotransmitters (<em>p</em> &lt; .05) and expression maps of specific genes. These enriched genes were implicated in excitatory neurons, inhibitory neurons, cellular metabolism, synapse function, and immune signaling. These findings were replicated on 2 brain atlases.</div></div><div><h3>Conclusions</h3><div>This work enhances our understanding of MDD and paves the way for the development of additional targeted therapeutic interventions.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 3","pages":"Pages 290-301"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104000","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":"An Astroglial Basis of Major Depressive Disorder: Molecular, Cellular, and Circuit Features","authors":"Cheng-Lin Lu ,&nbsp;Jing Ren ,&nbsp;Xiong Cao","doi":"10.1016/j.biopsych.2024.07.017","DOIUrl":"10.1016/j.biopsych.2024.07.017","url":null,"abstract":"<div><div>Major depressive disorder is a common psychiatric disorder and a leading cause of disability worldwide. Astrocytes play a role in the maintenance of the function of the central nervous system, both physiologically and pathologically. Accumulated evidence indicates that the astrocyte is an important contributor to the pathophysiology of major depressive disorder including blood-brain barrier integrity, gap junctions, gliotransmission, glutamate homeostasis, and energy metabolism. Here, we comprehensively summarize an astroglial basis for major depressive disorder based on molecular, cellular, and circuit properties, suggesting that astrocytes appear to be highly sensitive to stress and are likely to be uniquely positioned to integrate peripheral and central stress responses.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 3","pages":"Pages 217-226"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796767","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":"Subscribers Page","authors":"","doi":"10.1016/S0006-3223(24)01765-7","DOIUrl":"10.1016/S0006-3223(24)01765-7","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 3","pages":"Page A2"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143127900","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":"Two-Month Cognitive Changes Enhance Prediction of Non-Remission in Clinical High-Risk Individuals.","authors":"TianHong Zhang, YanYan Wei, XiaoChen Tang, LiHua Xu, HuiRu Cui, YeGang Hu, HaiChun Liu, ZiXuan Wang, Tao Chen, YingYing Tang, ZhengHui Yi, ChunBo Li, JiJun Wang","doi":"10.1016/j.biopsych.2025.01.021","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.021","url":null,"abstract":"<p><strong>Background: </strong>Longitudinal changes in cognitive function may be crucial in predicting clinical outcomes in clinical high risk (CHR) individuals. This study aims to investigate the predictive value of baseline cognitive impairment and short-term cognitive changes for non-remission and conversion to psychosis in individuals at CHR for psychosis, compared with healthy controls (HC).</p><p><strong>Methods: </strong>This study employed a multiple-group prospective design with a 3-year follow-up. CHR individuals and HCs were assessed at baseline and at a 2-month follow-up. Neuropsychological performance was evaluated using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery.</p><p><strong>Results: </strong>The study included 310 CHR individuals and 93 HCs. Significant improvements in predicting non-remission in CHR individuals were observed when incorporating cognitive changes over 2 months (AUC for baseline cognition, 0.690; AUC for changes, 0.819; Z=3.365, p<0.001). Key predictors included the Revised Hopkins Verbal Learning Test (HVLT-R; β=0.083, p=0.003), Wechsler Memory Scale-III spatial span (WMS-3; β=0.330, p<0.001), and Revised Brief Visuospatial Memory Test (BVMT-R; β=0.127, p<0.001). Conversely, predicting conversion to psychosis showed no significant difference between baseline and 2-month cognitive changes (AUC for baseline cognition, 0.667; AUC for changes, 0.666; Z=0.021, p=0.242).</p><p><strong>Conclusions: </strong>The findings underscore the importance of dynamic cognitive monitoring in CHR individuals. Short-term cognitive changes significantly enhance the prediction of non-remission but do not add predictive value for conversion to psychosis beyond baseline assessments. Specific cognitive domains, such as verbal learning and working memory, are particularly valuable for predicting clinical outcomes.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073623","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":"Comparative perspectives on neuropeptide function and social isolation.","authors":"Kenta Asahina, Moriel Zelikowsky","doi":"10.1016/j.biopsych.2025.01.019","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.019","url":null,"abstract":"<p><p>Chronic social isolation alters behavior across animal species. Genetic model organisms such as mice and flies provide crucial insight into the molecular and physiological effects of social isolation on brain cells and circuits. Here, we comparatively review recent findings regarding the function of conserved neuropeptides on social isolation in mice and flies. Analogous functions of three classes of neuropeptides - tachykinins, cholecystokinins, and neuropeptides Y/F - in the two model organisms, suggest that these molecules may be involved in modulating behavioral changes induced by social isolation across a wider range of species, including humans. Comparative approaches armed with tools to dissect neuropeptidergic function can lead to an integrated understanding of the impacts of social isolation on brain circuits and behavior.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073638","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":"Investigating the contribution of coding variants in alcohol use disorder using whole-exome sequencing across ancestries.","authors":"Lu Wang, Henry R Kranzler, Joel Gelernter, Hang Zhou","doi":"10.1016/j.biopsych.2025.01.020","DOIUrl":"10.1016/j.biopsych.2025.01.020","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use disorder (AUD) is a leading cause of death and disability worldwide. There has been substantial progress in identifying genetic variants underlying AUD. However, whole-exome sequencing (WES) studies of AUD are hampered by the lack of available samples.</p><p><strong>Methods: </strong>We analyzed WES data of 4,530 samples from the Yale-Penn cohort and 469,835 samples from the UK Biobank (UKB), which represents an unprecedented resource for exploring the contribution of coding variants in AUD. After quality controls, 2,039 European-ancestry (EUR: 1,420 cases) and 1,750 African-ancestry samples (AFR: 1,142 cases) from Yale-Penn, and 415,617 EUR samples (12,861‬ cases), 6,142 AFR samples (130 cases) and 4,607 South Asian (SAS) samples (130 cases) from UKB were included in the analyses.</p><p><strong>Results: </strong>We confirmed the well-known functional variant rs1229984 in ADH1B (P=4.88×10^-31) and several other variants in ADH1C. Gene-based collapsing tests considering the high allelic heterogeneity revealed the previously unreported genes, CNST (P=1.19×10^-6) attributable to rare variants with allele frequency < 0.001, and IFIT5 (P=3.74×10^-6) driven by the burden of both common and rare loss-of-function and missense variants.</p><p><strong>Conclusions: </strong>This study extends our understanding of the genetic architecture of AUD, by providing insights into the contribution of rare coding variants, separately and convergently with common variants in AUD.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073641","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":"Interneuron loss and microglia activation by transcriptome analyses in the basal ganglia of Tourette disorder.","authors":"Yifan Wang, Liana Fasching, Feinan Wu, Milovan Suvakov, Anita Huttner, Sabina Berretta, Rosalinda Roberts, James F Leckman, Thomas V Fernandez, Alexej Abyzov, Flora M Vaccarino","doi":"10.1016/j.biopsych.2024.12.022","DOIUrl":"10.1016/j.biopsych.2024.12.022","url":null,"abstract":"<p><strong>Background: </strong>Tourette disorder is characterized by motor hyperactivity and tics that are believed to originate in basal ganglia. Postmortem immunocytochemical analyses previously revealed decreases in cholinergic, parvalbumin, and somatostatin interneurons (IN) within the caudate/putamen of individuals with TS.</p><p><strong>Methods: </strong>We obtained transcriptome and open chromatin datasets by snRNAseq and snATAC-seq, respectively, from caudate/putamen postmortem specimens of 6 adult TS and 6 matched normal control (NC). Differential gene expression and differential chromatin accessibility analyses were performed in identified cell types.</p><p><strong>Results: </strong>The data reproduced the known cellular composition of the human striatum, including a majority of medium spiny neurons (MSN) and small populations of GABAergic and cholinergic IN. IN were decreased by ∼50% in TS brains, with no difference in other cell types. Differential gene expression analysis suggested that mitochondrial oxidative metabolism in MSN and synaptic adhesion and function in IN were both decreased in TS subjects, while there was activation of immune response in microglia. Gene expression changes correlated with changes in activity of cis-regulatory elements, suggesting a relationship of transcriptomic and regulatory abnormalities in MSN, OL and AST of TS brains.</p><p><strong>Conclusions: </strong>This initial analysis of the TS basal ganglia transcriptome at the single cell level confirms the loss and synaptic dysfunction of basal ganglia IN, consistent with in vivo basal ganglia hyperactivity. In parallel, oxidative metabolism was decreased in MSN and correlated with activation of microglia cells, attributable at least in part to dysregulated activity of putative enhancers, implicating altered epigenomic regulation in TS.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073639","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":"Hippocampal DNA methylation promotes contextual fear memory persistence by facilitating systems consolidation and cortical engram stabilization.","authors":"Janina Kupke, Stefanos Loizou, C Peter Bengtson, Carsten Sticht, Ana M M Oliveira","doi":"10.1016/j.biopsych.2025.01.016","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.016","url":null,"abstract":"<p><strong>Background: </strong>Long-term fear memory storage involves gradual reorganization of supporting brain regions over time, a process termed systems consolidation. Memories initially rely on the hippocampus but gradually shift dependence to the neocortex. Although hippocampal activity drives this transfer, the molecular basis of systems consolidation is largely unknown. DNA methylation changes accompany persistent fear memory formation in the hippocampus and cortex, but its causal role in memory storage and systems consolidation remains unclear.</p><p><strong>Methods: </strong>We investigated the role of hippocampal DNA methylation in fear memory persistence through multiple approaches. Using rAAV-mediated gene transfer, we overexpressed or knocked down a DNA methyltransferase (Dnmt3a2) in the dorsal hippocampus of mice and assessed its impact on fear memory duration. Engram tagging and manipulation tools were applied to study cortical fear engram stabilization. Finally, RNA-sequencing analysis was used to identify transcriptional changes driven by Dnmt3a2 overexpression.</p><p><strong>Results: </strong>Overexpression of hippocampal Dnmt3a2 induced a persistent fear memory, while its knockdown impaired remote memory recall. RNA-sequencing revealed that Dnmt3a2 overexpression modifies the expression of synaptic transmission regulatory genes. Furthermore, genetic engram tagging, and manipulation revealed that hippocampal DNA methylation promotes the transfer of the fear memory trace from the hippocampus to the cortex and the stabilization of cortical fear memory traces.</p><p><strong>Conclusion: </strong>Our findings demonstrate that hippocampal DNA methylation regulates the long-term storage of persistent fear memories by facilitating the transfer of memory traces from the hippocampus to cortex and cortical stabilization. These results highlight DNA methylation as a key molecular mechanism underlying systems consolidation and long-term fear memory storage.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063399","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":"Grasping Post-Traumatic Stress Disorder (PTSD) from the Perspective of Psychoneuroimmunoendocrinology (PNIE): Etiopathogenic Mechanisms and Relevance for the Integrative Management.","authors":"Oscar Fraile-Martinez, Cielo García-Montero, Miguel Ángel Álvarez-Mon, Carlos Casanova-Martín, Daniel Fernández-Faber, Marta Presa, Guillermo Lahera, Laura Lopez-Gonzalez, Raúl Díaz-Pedrero, José V Saz, Melchor Álvarez-Mon, Miguel A Sáez, Miguel A Ortega","doi":"10.1016/j.biopsych.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.014","url":null,"abstract":"<p><p>Post-Traumatic Stress Disorder (PTSD) is a debilitating condition caused by exposure to traumatic events, affecting 5-10% of the population, with increased prevalence among women and individuals in war zones. Beyond psychological symptoms, PTSD induces significant physiological changes across systems. Psychoneuroimmunoendocrinology (PNIE) offers a framework to explore these complex interactions between the psyche and the nervous, immune, and endocrine systems. Studies reveal that PTSD entails disruptions in the central and autonomic nervous, immune, and endocrine systems, including gut microbiota imbalances, impairing organ function. Integrative pathways connecting these parts include the microbiota-gut-brain axis, heart-brain axis, neuroinflammation, and hypothalamic-pituitary dysregulation, highlighting bidirectional links between mental and physical health. Viewing PTSD as a entity comprising both psychological and physiological challenges underscores the importance of integrative care strategies, combining pharmacological treatments, psychotherapy, and lifestyle interventions. These approaches align with PNIE principles, which may help identify biomarkers for treatment efficacy. This review discusses the pathophysiology of PTSD through a PNIE lens and its implications for improving patient care, advocating for personalized, multidisciplinary interventions in mental health.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045015","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}