Biological Psychiatry最新文献

{"title":"From Snapshots to Stable Outcomes: rs-fMRI-based Prognosis of Functioning in Patients with Psychosis Risk or Recent-Onset Depression.","authors":"Madalina-Octavia Buciuman, Shalaila S Haas, Linda A Antonucci, Elif Sarisik, Adyasha Khuntia, Theresa Lichtenstein, Marlene Rosen, Joseph Kambeitz, Christos Pantelis, Rebekka Lencer, Alessandro Bertolino, Paolo Brambilla, Rachel Upthegrove, Stephen J Wood, Peter Falkai, Anita Riecher-Rössler, Stephan Ruhrmann, Frauke Schultze-Lutter, Eva Meisenzahl, Jarmo Hietala, Raimo K R Salokangas, Stefan Borgwardt, Dominic B Dwyer, Lana Kambeitz-Ilankovic, Nikolaos Koutsouleris","doi":"10.1016/j.biopsych.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.07.003","url":null,"abstract":"<p><strong>Background: </strong>Early recovery of functioning is critical for favorable outcomes in psychotic and affective disorders. Transdiagnostic brain activity patterns may capture pathways for poor outcomes before clinical manifestation, supporting timely prevention and intervention.</p><p><strong>Methods: </strong>Using machine learning, we evaluated the transdiagnostic prognostic value of resting-state fMRI fractional amplitude of low-frequency fluctuations (fALFF, slow-5 and slow-4 sub-bands) for functional outcomes in patients at clinical high-risk for psychosis (n=217) or with recent-onset depression (n=198) from the multi-site PRONIA study. Leave-site-out cross-validation assessed geographic generalizability of models across disability and symptoms domains, with outcomes defined as 'snapshots' at 9- or 18-month follow-up or across both timepoints. We examined diagnosis-specific performance, generalization to recent-onset psychosis (ROP, n=140), and negative symptoms, and the added value of fALFF over clinical prognostication.</p><p><strong>Results: </strong>Transdiagnostic models predicting stable good functioning across follow-ups showed up to 10% higher balanced accuracy (BAC) than 'snapshot' models. Decreased slow-5 fALFF in the default-mode, executive control (EC), and dorsal attentional (DA) networks, and increased fALFF in salience, EC, and DA networks predicted impairment with BAC=67% (Sensitivity=65%, Specificity=70%, P<.001). This model generalized to ROP (BAC=62%, Sensitivity=64%, Specificity=59%, P<.001) and predicted (BAC=65%, Sensitivity=66%, Specificity=65%, P<.001) and was mediated by negative symptoms. Slow-5-based models improved prognostic accuracy over expert ratings in disability (BAC_raters=66%, BAC_{raters+slow-5}=75%, W=1680, P<.001) and symptoms domains (BAC_raters=61%, BAC_{raters+slow-5}=71%, W=1444, P<.001).</p><p><strong>Conclusions: </strong>We highlighted the prognostic value of fALFF for functional impairment in psychosis-risk and early depression. Leveraging trajectorial information, we identified candidate imaging biomarkers to improve prognostication, supporting personalized prevention and recovery strategies.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616117","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":"Getting Under the Skin: What Associations Between Polygenic Risk Scores of Complex Traits and Markers of Illness Course Can Tell Us About the Pathophysiology of Eating Disorders","authors":"Charles F. Gillespie","doi":"10.1016/j.biopsych.2025.05.023","DOIUrl":"10.1016/j.biopsych.2025.05.023","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 3","pages":"Pages 188-189"},"PeriodicalIF":9.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581146","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)01256-9","DOIUrl":"10.1016/S0006-3223(25)01256-9","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 3","pages":"Page A2"},"PeriodicalIF":9.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581150","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":"Guide for Authors","authors":"","doi":"10.1016/S0006-3223(25)01259-4","DOIUrl":"10.1016/S0006-3223(25)01259-4","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 3","pages":"Pages A5-A10"},"PeriodicalIF":9.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581148","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":"Mu Opioid Receptor Activation is Required for NMDA Receptor Antagonist Effects on Stress-induced Maladaptive Behavior.","authors":"Cory B Langreck, Briana Chen, Victor M Luna, Mel Nelson, Gergely Turi, Rob Hill, Gilles Rubinstenn, Meritxell Canals, J Robert Lane, Christine A Denny, Jonathan A Javitch","doi":"10.1016/j.biopsych.2025.07.004","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.07.004","url":null,"abstract":"<p><strong>Background: </strong>Contradictory evidence has emerged regarding the role of the mu opioid receptor (MOR) in the antidepressant actions of (R,S)-ketamine.</p><p><strong>Methods: </strong>Here, we used the long-acting MOR-selective antagonist methocinnamox (MCAM) to determine the contribution of MOR to the actions of (R,S)-ketamine and the more selective N-methyl-D-aspartate receptor (NMDAR) antagonist fluoroethylnormemantine (FENM) against stress-induced maladaptive behaviors. (R,S)-ketamine enantiomers and metabolites and FENM were assessed for their ability to directly activate MOR in cell signaling assays. (R,S)-ketamine and FENM were tested in various behavioral paradigms with vehicle or MCAM pretreatment. Patch clamp electrophysiology was used to determine the effects of MOR antagonism on ventral hippocampal cornu ammonis (CA3) glutamatergic activity after (R,S)-ketamine administration.</p><p><strong>Results: </strong>(R,S)-ketamine and its enantiomers showed weak partial agonism of MOR, whereas the potency and efficacy of FENM were negligible. The antinociceptive effect of (R,S)-ketamine were both more potent and more sensitive to blockade by MCAM than that of FENM. When given either before or after stress, both (R,S)-ketamine and FENM reduced behavioral despair. MCAM prevented the effects of both NMDAR antagonists given before or after stress, despite their differences in direct MOR activity and antinociception.</p><p><strong>Conclusions: </strong>MOR activation is required for the efficacy of both (R,S)-ketamine and FENM against stress-induced maladaptive behavior, suggesting that these compounds function through an indirect effect of NMDAR antagonism on endogenous opioid signaling.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599200","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":"Impact of inflammation on white matter integrity and functional connectivity in chronic major depressive disorder.","authors":"Jungho Cha, Divyaansh Raj, Ki Sueng Choi, Justin K Rajendra, Charles B Nemeroff, Jennifer C Felger, W Edward Craighead, Helen S Mayberg, Boadie W Dunlop","doi":"10.1016/j.biopsych.2025.06.026","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.026","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is increasingly recognized as a pathophysiologic component of major depressive disorder (MDD). Concurrently, depressive episode chronicity has emerged as a significant predictor of adverse long-term outcomes.</p><p><strong>Methods: </strong>Utilizing data from the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study, our analysis included 201 participants who completed C-reactive protein (CRP) sampling and diffusion-weighted imaging scans, of whom 120 participants had usable functional magnetic resonance imaging scans. Chronicity was classified as the presence of a current depressive episode ≥2 years in duration. We examined the impact of inflammation on brain structure and function in MDD, focusing specifically on differences related to chronicity, as well as the interactions between inflammation, functional, and structural alterations.</p><p><strong>Results: </strong>No significant correlations were observed between CRP concentrations and either functional connectivity (FC) or fractional anisotropy (FA). In chronic, but not non-chronic, MDD patients, higher CRP concentrations were associated with lower FA in several neural pathways, including cingulum and frontal aslant tracts. Significant CRP by MDD chronicity interactions were also observed for FC within the default mode network (DMN) and the salience network (SN). Moreover, mediation analyses demonstrated both direct and FA-mediated effects of CRP on FC within the SN in chronic patients.</p><p><strong>Conclusions: </strong>Interactions based on depressive episode chronicity between CRP and neurobiological function, potentially mediated by reductions in WM integrity, suggest a potential pathophysiological process in some chronic MDD patients. The differences in FC suggest specific compensatory adjustments within DMN and SN among chronic MDD patients.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599199","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":"Exploring the pathways between early auditory processing, processing speed, social cognition, and negative symptoms on social functioning in individuals at clinical high risk for psychosis: A structural equation modeling approach.","authors":"Ricardo E Carrión, Majnu John, Sarah Dorvil, Andrea Auther, Danielle McLaughlin, Mitchell Arnovitz, Peter Bachman, Aysenil Belger, Erica Duncan, Holly Hamilton, Jason Johannesen, Benson Ku, Gregory Light, Margaret Niznikiewicz, Brian J Roach, Jean Addington, Carrie E Bearden, Kristin S Cadenhead, Tyrone D Cannon, Matcheri Keshavan, Diana O Perkins, William S Stone, Ming Tsuang, Elaine F Walker, Scott W Woods, Daniel H Mathalon, Barbara A Cornblatt","doi":"10.1016/j.biopsych.2025.06.033","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.033","url":null,"abstract":"<p><strong>Introduction: </strong>Social functioning difficulties in adolescents and young-adults at clinical high-risk for psychosis (CHR-P) are among the strongest risk factors for psychosis onset. Recent research in patients with schizophrenia has demonstrated complex relationships between early auditory processing deficits as measured by the Mismatch Negativity (MMN) response of the auditory event-related potential (ERP), neurocognition, social cognition, negative symptoms, and social functioning. However, the interrelationships of these variables and associations with social functioning impairments prior to the onset of the illness are unclear. The present study used a structural equation modeling (SEM) approach to integrate these factors to determine the specific determinants that lead to poor social functioning in CHR-P youth.</p><p><strong>Methods: </strong>518 CHR-P individuals from the North American Prodrome Longitudinal Study (NAPLS2) were used to evaluate SEMs with pathways starting from MMN to social functioning. The intervening variables included processing speed, social cognition, and negative symptoms.</p><p><strong>Results: </strong>A final trimmed model revealed that early auditory processing (MMN) had a direct effect on processing speed, and both processing speed and negative symptoms had direct effects on social functioning. The direct effect from social cognition to social functioning was not significant.</p><p><strong>Conclusions: </strong>Our findings suggest that neurophysiological deficits are associated with social functioning by way of processing speed impairments, which fully accounted for the relationship, in CHR-P youth prior to psychosis onset. These results may have implications for early intervention strategies that target early information processing deficits with the aim of improving social trajectories and limiting psychosis onset in young CHR-P individuals.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599197","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":"Biologically Annotated Heterogeneity of Depression through Neuroimaging Normative Modeling.","authors":"Jiao Li, Huafu Chen, Wei Liao","doi":"10.1016/j.biopsych.2025.07.002","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.07.002","url":null,"abstract":"<p><p>Depression is not a unitary disorder but is rather heterogeneous in nature. Likewise, no two depressive individuals are entirely alike, and therefore, their associated symptoms are also highly personalized. Over the past decade, numerous approaches have been developed to identify neuroimaging-derived biomarkers for advancing our understanding of the neurobiology of depressive patients at the group level. However, substantial clinical heterogeneity among individuals with depression hinders the development of biomarkers for personalized interventions. Recently, publicly available resources have enabled researchers to investigate precision neuromarkers for depression using integrative multi-neuroimaging approaches. In this review, we systematically revisit previous findings and discuss the advances in data-driven neuroimaging analyses for depression heterogeneity, including the disentangling of dimensional and overlapping strategies, individual-specific abnormal patterns based on normative modeling frameworks, and associations between multiscale organizations. We also discuss the limitations, challenges, and future directions for depression heterogeneity. A summary of these advances is crucial for enhancing the understanding of the neurobiology of depression and will facilitate more accurate diagnoses and personalized interventions.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599163","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":"Attraction through similarity in autistic traits: A group communication study using social relations model and fNIRS hyperscanning.","authors":"Shuyuan Feng, Mingliang Wang, Jianing Zhang, Lin Ding, Yuqing Yuan, Peng Zhang, Xuejun Bai","doi":"10.1016/j.biopsych.2025.06.031","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.031","url":null,"abstract":"<p><strong>Background: </strong>The double empathy problem (DEP) reconceptualizes autism's social challenges as bidirectional differences rather than unidirectional deficits. Following the DEP, the dialectical misattunement hypothesis (DMH) predicts that interaction between people with similar autistic traits will be smoother and reflected in neural synchronization. However, evidence remains inconsistent due to methodological limitations in dyadic designs and unstructured tasks, and it remains unclear whether neural mechanisms differ between passive and active social contexts across autistic trait levels.</p><p><strong>Methods: </strong>Using the social relations model, we measured the relational attraction within four-person groups (20 female and 10 male groups), composed of two high-autistic-trait individuals and two low-autistic-trait individuals following a turn-taking discussion. Simultaneously, we recorded brain activity using functional near-infrared spectroscopy (fNIRS) during both passive story listening and active turn-taking discussion.</p><p><strong>Results: </strong>Individuals with similar autistic traits reported higher interpersonal attraction when sharing consistent opinions. Neural analyses revealed context-dependent interbrain coupling patterns: During passive story listening, low-autistic-trait dyads exhibited higher inter-subject correlation (ISC) compared to high-autistic-trait dyads. In contrast, during active communication, low-autistic-trait dyads exhibited higher interbrain synchronization (IBS) in the right temporoparietal junction, while high-autistic-trait dyads showed higher IBS in the right dorsolateral prefrontal cortex, suggesting distinct neural mechanisms underlying social interaction across autistic trait levels.</p><p><strong>Conclusions: </strong>Our findings support the DMH and reveal that neural synchronization mechanisms vary across both autistic trait levels and social contexts. These context-dependent patterns challenge deficit-based models of autism, suggesting that high-autistic-trait individuals may employ alternative but effective neural strategies during social interaction, particularly in active communication contexts.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599162","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":"Shedding Light on Brain Function and Mood: A Role for the Retinoraphe Pathway in Regulating Serotonin.","authors":"Kornelija Vitkute, Francesca Borghese, Roelof A Hut, Robbert Havekes, Peter Meerlo","doi":"10.1016/j.biopsych.2025.06.029","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.029","url":null,"abstract":"<p><p>Light has the capacity for immediate and long-term modulation of complex neuronal systems and brain function. While correct timing of light exposure is essential for optimal physical and mental performance, insufficient light or light at the wrong time has been associated with mood related detriments. In humans, affective disorders have been linked to a dysfunction of the serotonergic system but the neuronal correlates linking mood and serotonin with effects of light remain elusive. In this review, we discuss the potential importance of the retinoraphe pathway, a direct neuronal connection between the retina and the dorsal raphe, the largest serotonergic nucleus in the brain stem. We discuss current knowledge on the cellular composition, innervation patterns, working mechanisms and functional outputs of the retinoraphe system across different animal species. While this connection has not been extensively investigated in humans, indirect evidence suggests that the retinoraphe pathway may be at the center of the mechanistic wiring that mediates the effects of light on physiology and mood.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599202","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}