Biological Psychiatry最新文献

{"title":"Her and His Responses to Social Defeat Stress: One Metric Does Not Fit All","authors":"Georgia E. Hodes","doi":"10.1016/j.biopsych.2025.06.015","DOIUrl":"10.1016/j.biopsych.2025.06.015","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 5","pages":"Pages 373-375"},"PeriodicalIF":9.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144781503","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":"Sleep Neurophysiology in Depression.","authors":"Yevgenia Rosenblum, Juan Nakagawa, Timo van Hattem, Elena Krugliakova, Bagmish Sabhapondit, Leonore Bovy, Thorsten Mikoteit, Axel Steiger, Marcel Zeising, Martin Dresler","doi":"10.1016/j.biopsych.2025.07.023","DOIUrl":"10.1016/j.biopsych.2025.07.023","url":null,"abstract":"<p><p>Sleep disturbances are both a primary symptom of and risk factor for major depressive disorder (MDD). Sleep alterations in MDD include the presence of insomnia or hypersomnia and aberrations in sleep macro- and microstructure, including a reduced latency until and prolonged duration of the first rapid eye movement (REM) episode, decreased slow-wave sleep (SWS), disturbed sleep continuity, and decreased steepening of aperiodic neural activity. MDD sleep is also characterized by dysfunctional autonomic cardiac activity as reflected by decreased heart rate variability. Sedating and novel antidepressants may improve sleep continuity and SWS while activating antidepressants tend to suppress REM sleep. Cognitive processing during sleep may contribute to MDD symptomatology; however, empirical research in this direction is still inconclusive. The rapid effects of antidepressants on sleep structure and of acute sleep deprivation on MDD symptoms suggest an intimate association between sleep and MDD neuropathology; however, the underlying mechanisms still need to be elucidated. This narrative review aims to provide a comprehensive overview of our current understanding of the physiology of sleep alterations in MDD and to discuss how sleep may play a role in current therapeutic approaches while also identifying novel strategies for modulating sleep in the context of depression. It seeks to offer a well-rounded foundation of the current knowledge on sleep and depression to guide basic and clinical scientists in future investigations related to improving existing and developing novel sleep-based therapeutic interventions.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793391","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":"Lifespan Normative Models of White Matter Fractional Anisotropy: Applications to Early Psychosis.","authors":"Ramona Cirstian, Natalie J Forde, Hui Zhang, Gerhard S Hellemann, Christian F Beckmann, Nina V Kraguljac, Andre F Marquand","doi":"10.1016/j.biopsych.2025.07.021","DOIUrl":"10.1016/j.biopsych.2025.07.021","url":null,"abstract":"<p><strong>Background: </strong>This study presents large-scale normative models of white matter (WM) organization across the lifespan, using diffusion magnetic resonance imaging data from over 25,000 healthy individuals ages 0 to 100 years from multiple cohorts including the Human Connectome Project (HCP) Lifespan and UK Biobank. These models capture lifespan trajectories and interindividual variation in fractional anisotropy (FA), a marker of WM integrity.</p><p><strong>Methods: </strong>By addressing non-Gaussian data distributions, self-reported race, and site effects, the models offer reference baselines across diverse ages and scanning conditions. We applied these FA models to the HCP Early Psychosis cohort and performed a multivariate analysis to map symptoms onto deviations from multimodal normative models using multiview sparse canonical correlation analysis.</p><p><strong>Results: </strong>Our results reveal extensive WM heterogeneity in psychosis, which is not captured by group-level analyses, with key regions identified, including the right uncinate fasciculus and thalami.</p><p><strong>Conclusions: </strong>These normative models offer valuable tools for individualized WM deviation identification, improving precision in psychiatric assessments. All models are publicly available for community use.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774677","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":"Urolithin A Abolishes High Anxiety and Rescues the Associated Mitochondria-Related Transcriptomic Signatures and Synaptic Function.","authors":"David Mallet, Doğukan H Ülgen, Jocelyn Grosse, Olivia Zanoletti, Isabelle Guillot de Suduiraut, Anna S Monzel, Davide D'Amico, Chris Rinsch, Martin Picard, Simone Astori, Carmen Sandi","doi":"10.1016/j.biopsych.2025.07.020","DOIUrl":"10.1016/j.biopsych.2025.07.020","url":null,"abstract":"<p><strong>Background: </strong>Chronic anxiety is common, disabling, and often refractory to current therapies. Mounting evidence implicates mitochondrial abnormalities in anxiety-related phenotypes. Urolithin A (UA), a gut microbiota-derived metabolite known to enhance mitochondrial health, has shown neuroprotective effects. However, its potential to alleviate anxiety remains unexplored.</p><p><strong>Methods: </strong>UA was administered chronically to two validated rodent models of high anxiety: 1) outbred animals displaying natural variation in trait anxiety and 2) rats selectively bred for high stress reactivity; low-anxiety animals served as controls. Anxiety-like behaviors were assessed across multiple tasks. Molecular profiling of nucleus accumbens (NAc) medium spiny neurons (MSNs) was performed using single-nucleus RNA sequencing, with MitoPathway analysis to evaluate mitochondria-related transcriptomic signatures. Electrophysiological, immunohistochemical, and morphological approaches were used to assess synaptic and structural correlates.</p><p><strong>Results: </strong>UA produced a robust anxiolytic effect in both high-anxiety models in both sexes without altering behavior in low-anxiety animals. High-anxiety MSNs displayed coupled dysregulation of mitochondrial and synaptic gene pathways that UA normalized to low-anxiety levels across MSN subtypes. These changes were accompanied by structural and functional rescue of MSN dendritic architecture, spine density, and excitatory synaptic transmission. Notably, UA also restored expression of Mfn2, a mitochondrial protein causally involved in the regulation of anxiety-related behavior and circuit dysfunction in the NAc, further supporting a mechanistic link between mitochondrial remodeling and UA's anxiolytic efficacy.</p><p><strong>Conclusions: </strong>These findings position UA as a mechanistically supported intervention in preclinical models of heightened anxiety and provide systems-level insights into how mitochondrial pathways interface with synaptic function and circuit regulation in anxiety states.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768289","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":"Efficacy and Safety of Accelerated Intermittent Theta-burst Stimulation for Adolescents with Major Depressive Disorder: A Randomized, Double-Blind, Sham-controlled study.","authors":"Xiaoli Liu, Ziyang Peng, Fang Cheng, Guangxue Li, Beini Wang, Changzhou Hu, Zhenzhen Zhu, Shasha Hu, Xinliang Luo, Jianzhou Sun, Shujun Wang, Jun Fu, Wenwu Zhang, Dongsheng Zhou","doi":"10.1016/j.biopsych.2025.07.018","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.07.018","url":null,"abstract":"<p><strong>Background: </strong>Developing safe and rapid treatments is crucial for adolescent major depressive disorder (MDD). While 10-session daily accelerated intermittent theta burst stimulation (a-iTBS) is effective in adults, its duration and safety limit its use in adolescents. This study evaluated a five-session daily a-iTBS protocol for adolescents with non-treatment-resistant MDD.</p><p><strong>Method: </strong>Seventy-four adolescents with non-treatment-resistant MDD were randomly assigned in a-iTBS or sham group. The a-iTBS group underwent five sessions of 1800-pulse iTBS per day targeting the left dorsolateral prefrontal cortex (DLPFC; Montreal Neurological Institute [MNI] coordinates: -44, 40, 29) using neuronavigation for ten consecutive days, while the sham group received intervention with a sham coil that provided haptic sensations and audible sounds. The 17-item Hamilton Depression Scale (HAMD-17), Hamilton Anxiety Scale (HAMA) and Children's Depression Inventory (CDI) were rated at baseline, the first day after the innervation (day 11), and the month 1 and 3 follow-up.</p><p><strong>Results: </strong>The a-iTBS group showed a significantly greater reduction in HAMD-17 compared with the sham group at day 11 (P < .001, Cohen'd = 0.86 [95% CI: 0.38, 1.33]) and month 1 follow-up (Cohen'd = 0.72 [95% CI: 0.24,1.18]). However, there was no statistically significant between the two groups at month 3 follow-up (P = .17, Cohen's d = 0.33 [95% CI: -0.13, 0.79]). The a-iTBS group showed significantly greater improvements in anxiety and self-reported depression at all time points compared to the sham group (all P-values < .05).</p><p><strong>Conclusion: </strong>A-iTBS is a safe and effective treatment for adolescents with non-treatment-resistant MDD, but the therapeutic effect diminished at the month 3 follow-up.</p><p><strong>Limitation: </strong>Although the study was blinded, clinician identification exceeded random chance in the a-iTBS group, suggesting that blinding may have been partially compromised.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752238","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":"Activity of Corticotropin-Releasing Factor Neurons in the Bed Nucleus of the Stria Terminalis Reduces Anxiety-Potentiated Startle in Female Rats in an Estrous Phase-Dependent Manner.","authors":"Rachel Chudoba, Joanna Dabrowska","doi":"10.1016/j.biopsych.2025.07.017","DOIUrl":"10.1016/j.biopsych.2025.07.017","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of posttraumatic stress disorder (PTSD) and anxiety disorders is higher in women than men. The severity of hallmark symptoms including hypervigilance and fear reactivity to unpredictable threats varies with sex and reproductive cycle, but the underlying mechanisms remain unclear. Here, we investigated corticotropin-releasing factor (CRF) neurons in the dorsolateral bed nucleus of the stria terminalis (BNST_DL) as a potential nexus for the influence of biological sex and reproductive cycle on fear- and anxiety-related behaviors.</p><p><strong>Methods: </strong>A total of 125 male and 156 cycle-monitored female CRF-Cre rats were used. BNST_DL-CRF neuron excitability and synaptic activity were recorded with slice electrophysiology. Chemogenetic manipulations of BNST_DL-CRF neurons were performed before elevated plus maze, predator odor exposure, shock-induced startle sensitization, and anxiety-potentiated startle (APS) following unpredictable fear conditioning.</p><p><strong>Results: </strong>BNST_DL-CRF neurons in females exhibited higher excitability (cycle independent) and lower sensitivity to excitatory synaptic inputs (proestrus and diestrus) than males. BNST_DL-CRF neuron inhibition reduced open-arm time in estrus females but not males. In the APS, BNST_DL-CRF neuron inhibition attenuated short-term startle potentiation in males, whereas it caused persistent APS in diestrus females. Notably, chemogenetic activation of BNST_DL-CRF neurons reduced APS in diestrus females.</p><p><strong>Conclusions: </strong>Unpredictable fear conditioning elicits sex- and estrous phase-specific APS, differentially regulated by BNST_DL-CRF neurons. Persistent APS in females aligns with hormonal phases marked by low levels of reproductive hormones, mirroring human PTSD findings. Widely used in human studies, APS may bridge animal and human research, supporting the development of biomarkers and more effective pharmacotherapies.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752237","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":"Transposable Elements Are Dynamically Regulated in Medium Spiny Neurons and May Contribute to the Molecular and Behavioral Adaptations to Cocaine.","authors":"Gabriella M Silva, Amber L Kaplan, Celeste R Park, Joseph A Picone, R Kijoon Kim, Natalie L Truby, Rachel L Neve, Xiaohong Cui, Peter J Hamilton","doi":"10.1016/j.biopsych.2025.07.014","DOIUrl":"10.1016/j.biopsych.2025.07.014","url":null,"abstract":"<p><strong>Background: </strong>Earlier work has established that Zfp189, which encodes a KZFP transcription factor (TF), differentially accumulates in nucleus accumbens (NAc) Drd1+ and Drd2+ medium spiny neurons (MSNs) and drives MSN functional and behavioral adaptations to cocaine. Here, we aimed to illuminate the cell type mechanisms through which this TF contributes to cocaine adaptations, with emphasis on investigating transposable elements (TEs).</p><p><strong>Methods: </strong>First, we annotated TEs in existing single-nucleus RNA sequencing (snRNAseq) from rodents exposed to either acute or repeated cocaine. To directly test whether TE dysregulation participates in cocaine-related brain changes, we virally delivered synthetic ZFP189 TFs, capable of releasing (ZFP189^VPR) or repressing (ZFP189^WT) brain TEs. Following cocaine exposure, we performed both bulk and snRNAseq of manipulated NAc. Lastly, we conditionally delivered these synthetic TFs to either the Drd1+ or Drd2+ MSNs and performed behavioral and cell morphological experiments.</p><p><strong>Results: </strong>We discovered that NAc TE transcript expression was dramatically increased by cocaine experience, and the most sensitive NAc cell types were Drd1+, followed by Drd2+ MSNs. Our snRNAseq revealed that ZFP189^VPR impeded gene expression across NAc cell types, including both MSN subtypes. Within either MSN subtype, ZFP189^WT promoted, and ZFP189^VPR restricted, primarily immune-related gene expression. We discovered that behavioral and cell morphological adaptations to cocaine are potentiated by ZFP189^VPR function in Drd1+ MSNs or ZFP189^WT in Drd2+ MSNs, revealing an MSN opponent process weighted by ZFP189 function.</p><p><strong>Conclusions: </strong>This research points to TE transcript expression as dynamically regulated within NAc MSNs and possibly involved in producing the molecular and behavioral responses to cocaine.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727296","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":"Guide for Authors","authors":"","doi":"10.1016/S0006-3223(25)01283-1","DOIUrl":"10.1016/S0006-3223(25)01283-1","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 4","pages":"Pages A5-A10"},"PeriodicalIF":9.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685568","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":"Editorial Board Page","authors":"","doi":"10.1016/S0006-3223(25)01279-X","DOIUrl":"10.1016/S0006-3223(25)01279-X","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 4","pages":"Page A1"},"PeriodicalIF":9.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685565","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(25)01280-6","DOIUrl":"10.1016/S0006-3223(25)01280-6","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 4","pages":"Page A2"},"PeriodicalIF":9.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685566","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}