Biological Psychiatry最新文献

{"title":"Subscribers Page","authors":"","doi":"10.1016/S0006-3223(26)01300-4","DOIUrl":"10.1016/S0006-3223(26)01300-4","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"100 2","pages":"Page A2"},"PeriodicalIF":10.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148529148","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":"Vision and Psychosis: A Clinical Translational Perspective","authors":"Halide Bilge Türközer,&nbsp;Paulo Lizano,&nbsp;Carol A. Tamminga,&nbsp;Steven M. Silverstein","doi":"10.1016/j.biopsych.2025.11.005","DOIUrl":"10.1016/j.biopsych.2025.11.005","url":null,"abstract":"<div><div>The visual system, as one of the most well understood components of the central nervous system, offers a unique framework for understanding mechanistic aspects of psychosis. In this review, we explore the clinical translational potential of visual system alterations in psychosis spectrum disorders, emphasizing their relevance across neurodevelopmental and neurodegenerative processes. The current evidence supporting the clinical significance of visual alterations is reviewed, covering aspects from the retina to low- and mid-level visual regions of the brain and emphasizing the feasibility, accessibility, and cost-effectiveness of vision science tools. We also discuss the therapeutic promise of visual system assessments for guiding personalized treatments, monitoring responses to novel pharmacological agents, and advancing approaches such as visual remediation and noninvasive brain stimulation to target vision-related symptoms in psychosis spectrum disorders. By addressing current gaps and proposing a roadmap for integrating these tools into psychiatric research and clinical care, this review underscores the significant potential of leveraging the visual system to enhance diagnostic precision and improve clinical outcomes in psychosis spectrum disorders.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"100 2","pages":"Pages 140-149"},"PeriodicalIF":10.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531205","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":"TAAR1 Regulates Presynaptic Dopamine Function: Evidence From Preclinical Studies and a Phase 1b Trial in Patients With Schizophrenia","authors":"Oliver D. Howes,&nbsp;Luke J. Vano,&nbsp;Alice E. Petty,&nbsp;Grazia Rutigliano,&nbsp;Els F. Halff,&nbsp;Mattia Veronese,&nbsp;Stephen J. Kaar,&nbsp;Giovanna Nordio,&nbsp;Emanuel F. Lopes,&nbsp;Stephanie J. Cragg,&nbsp;Sridhar Natesan,&nbsp;Dominic J. Withers,&nbsp;Eugenii A. Rabiner,&nbsp;Lisa Wells,&nbsp;Nina Dedic,&nbsp;Snezana Milanovic,&nbsp;Kenneth Koblan,&nbsp;Seth C. Hopkins,&nbsp;Robert A. McCutcheon","doi":"10.1016/j.biopsych.2025.10.013","DOIUrl":"10.1016/j.biopsych.2025.10.013","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia remains a leading cause of disability globally. Elevated striatal dopamine (DA) synthesis capacity is a hallmark of its pathophysiology, but it is unknown whether this can be reduced and whether such reductions lead to symptom improvement. TAAR1 may regulate dopaminergic function, and ulotaront (SEP-363856), a TAAR1 agonist, offers a potential novel treatment strategy.</div></div><div><h3>Methods</h3><div>We conducted combined translational preclinical and clinical tests of mechanism studies. Preclinical work involved TAAR1 knockout (KO) and wild-type (WT) mice (<em>N</em> = 27), as well as ex vivo striatal brain slices. In a phase 1 open-label trial, 22 patients with symptomatic schizophrenia (mean age = 32.5 years; 72.7% male) received 14 days of adjunctive ulotaront treatment. DA synthesis capacity (K_i) was measured using [¹⁸F]-DOPA positron emission tomography in animals and humans. DA release in brain slices was assessed using fast-scan cyclic voltammetry.</div></div><div><h3>Results</h3><div>TAAR1-KO mice showed significantly higher striatal K_i than WT controls (<em>p</em> &lt; .05). Ulotaront reduced evoked DA release in brain slices after single (<em>p</em> &lt; .0005) and repeated (<em>p</em> &lt; .005) stimulation. In patients, ulotaront significantly reduced striatal K_i (<em>p</em> &lt; .01), particularly in the putamen. Reductions in K_i correlated with improvements in positive symptoms (<em>r</em> = 0.5, <em>p</em> &lt; .05) but not with changes in negative or total symptoms. The most common adverse events were somnolence and dizziness.</div></div><div><h3>Conclusions</h3><div>TAAR1 regulates DA synthesis and release. Adjunctive ulotaront reduces presynaptic DA function and psychotic symptoms in schizophrenia. These findings support TAAR1 as a promising target for treating antipsychotic nonresponsive schizophrenia and other dopaminergic disorders.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"100 2","pages":"Pages 199-207"},"PeriodicalIF":10.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353714","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":"Dynamic Brain States With Cannabis Intoxication: Beyond “More Is Better” in Interpreting Brain Connectivity","authors":"Jodi M. Gilman,&nbsp;Amy C. Janes","doi":"10.1016/j.biopsych.2026.05.005","DOIUrl":"10.1016/j.biopsych.2026.05.005","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"100 2","pages":"Pages 129-131"},"PeriodicalIF":10.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315472","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":"Brain Metabolite Levels in the Post-Acute Stage of Anti-NMDA Receptor Encephalitis and Schizophrenia: A Longitudinal Case-Control Study","authors":"Adriana Fortea,&nbsp;María Ortuño,&nbsp;Mireia Masias,&nbsp;Mar Guasp,&nbsp;Elena De la Serna,&nbsp;Thais Armangue,&nbsp;Inmaculada Baeza,&nbsp;Roger Borràs,&nbsp;Laia Prades,&nbsp;Mirea Rosa-Justicia,&nbsp;Heike Stein,&nbsp;Eloy Martínez-Heras,&nbsp;Albert Compte,&nbsp;Sara Llufriu,&nbsp;Josep Dalmau,&nbsp;Josefina Castro-Fornieles,&nbsp;Gisela Sugranyes","doi":"10.1016/j.biopsych.2025.07.006","DOIUrl":"10.1016/j.biopsych.2025.07.006","url":null,"abstract":"<div><h3>Background</h3><div>In vivo assessment of glutamatergic metabolites in patients with anti-NMDA receptor (anti-NMDAR) encephalitis compared with schizophrenia may help increase understanding of the pathophysiology of both conditions.</div></div><div><h3>Methods</h3><div>This 24-month prospective case-control study included participants ages 12 to 60 years with anti-NMDAR encephalitis during the post-acute stage and age- and sex-matched individuals with schizophrenia and healthy control participants (HCs). Single-voxel magnetic resonance spectroscopy was used to estimate brain concentrations of glutamatergic metabolites, myo-inositol, and <em>N</em>-acetylaspartate+<em>N</em>-acetylaspartylglutamate (tNAA) in the left dorsomedial prefrontal region (dmPF) and medial temporal lobe. The effect of group and time on metabolite levels and the relationship between metabolite levels and psychiatric and cognitive features were tested with multilevel linear mixed models.</div></div><div><h3>Results</h3><div>Thirty-two participants with anti-NMDAR encephalitis (84% women), 27 participants with schizophrenia (63% women), and 36 HCs (72% women) were included. In the dmPF, levels of glutamate and glutamate+glutamine were significantly lower in patients with anti-NMDAR encephalitis than in participants with schizophrenia (Cohen’s <em>d</em> = −0.87 and <em>d</em> = −0.80, respectively) and HCs (<em>d</em> = −0.73 and <em>d</em> = −0.71). Myo-inositol levels were significantly higher in both participants with anti-NMDAR encephalitis (<em>d</em> = 0.91) and patients with schizophrenia (<em>d</em> = 1.07) than in HCs. Group differences remained stable over time. Metabolite levels were not associated with psychiatric or cognitive symptoms.</div></div><div><h3>Conclusions</h3><div>This is the first report of hypoglutamatergia in the left dmPF in anti-NMDAR encephalitis and of increased levels of myo-inositol in both anti-NMDAR encephalitis and schizophrenia. The findings suggest persistent alterations in glutamatergic neurotransmission during the post-acute stage of anti-NMDAR encephalitis and overlapping neuroinflammatory processes between anti-NMDAR encephalitis and schizophrenia.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"100 2","pages":"Pages 189-198"},"PeriodicalIF":10.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621834","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":"Multivariate Resting-State Functional Connectivity Features Linked to Transdiagnostic Psychopathology in Early Psychosis","authors":"Haley R. Wang,&nbsp;Zhen-Qi Liu,&nbsp;Jason S. Nomi,&nbsp;Charles H. Schleifer,&nbsp;Carrie E. Bearden,&nbsp;Bratislav Misic,&nbsp;Lucina Q. Uddin,&nbsp;Katherine H. Karlsgodt","doi":"10.1016/j.biopsych.2025.10.024","DOIUrl":"10.1016/j.biopsych.2025.10.024","url":null,"abstract":"<div><h3>Background</h3><div>Early psychosis (EP) is characterized by neurobiological changes, including alterations in resting-state functional connectivity (RSFC). We now understand that symptoms and neural changes may overlap across EP diagnostic categories. However, the relationship between RSFC patterns and transdiagnostic symptom dimensions remains poorly understood.</div></div><div><h3>Methods</h3><div>We used partial least squares correlation to examine multivariate relationships between whole-brain RSFC and clinical symptoms in 124 patients with EP (ages 16–35 years) diagnosed with schizophrenia, schizoaffective disorder, or a psychotic mood disorder. RSFC was computed among 216 cortical and subcortical regions. Clinical assessment included 41 symptom measures spanning positive, negative, general psychopathology, and manic dimensions.</div></div><div><h3>Results</h3><div>Analysis revealed one significant latent component (<em>p</em> &lt; .001) capturing 41.6% of the RSFC symptom covariance. This component was characterized by increased between-network connectivity, particularly involving sensory-motor, default mode, and subcortical regions including the amygdala and thalamus. The associated symptom profile included cognitive rigidity and arousal dysregulation (stereotyped thinking, anxiety, and somatic concerns) rather than traditional positive or negative symptoms. This brain-behavior relationship was consistent across diagnoses and independent of medication and substance use. The clinical relevance of this relationship was validated through significant correlations with standardized measures of hostility (<em>r</em> = 0.23), negative affect (<em>r</em> = 0.25), and perceived stress (<em>r</em> = 0.22).</div></div><div><h3>Conclusions</h3><div>Our findings reveal a distinct transdiagnostic phenotype in EP characterized by cognitive inflexibility and arousal dysregulation that is associated with altered integration between sensory, default mode, and subcortical networks. This work suggests that specific patterns of network-level FC may relate to symptom dimensions that cut across conventional diagnostic boundaries, potentially informing more targeted therapeutic approaches.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"100 2","pages":"Pages 178-188"},"PeriodicalIF":10.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145383818","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(26)01302-8","DOIUrl":"10.1016/S0006-3223(26)01302-8","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"100 2","pages":"Pages A5-A11"},"PeriodicalIF":10.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148529151","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":"Mega-Analysis of Structural Brain Imaging in Functional Neurological Disorder.","authors":"Matt Butler, Miriam Vignando, Jane B Allendorfer, Thomas Hassa, Silvina G Horovitz, Jacobus F A Jansen, Johannes Jungilligens, Wesley T Kerr, Ramesh S Marapin, Enrico Premi, Aleksandar J Ristic, Tereza Serranova, Petr Sojka, Daichi Sone, Barbara Borroni, Anthony David, Quinton Deeley, Ibai Diez, Sara Paredes Echeverri, Dawn S Elashiv, Jeannette M Gelauff, Mark Hallett, Richard Kanaan, Marina A J de Koning-Tijssen, Madeleine Love, Mauro Magoni, Kirpal Sadheura, Noriko Salamon, Noriko Sato, Ariel Schoenfeld, John M Stern, Jerzy P Szaflarski, David L Perez, Selma Aybek, Mitul A Mehta, Timothy Nicholson","doi":"10.1016/j.biopsych.2026.06.031","DOIUrl":"10.1016/j.biopsych.2026.06.031","url":null,"abstract":"<p><strong>Background: </strong>Despite recent advances, the pathophysiology of functional neurological disorder (FND) remains incompletely understood. Structural neuroimaging studies have identified gray matter alterations in somatomotor-, salience-, limbic-, and default mode network-associated areas, although findings have been inconsistent. Mega-analyses, which combine individual-level data across studies, can help clarify structural alterations.</p><p><strong>Methods: </strong>We conducted a mega-analysis of brain structural morphometrics derived from T1-weighted magnetic resonance imaging scans from 15 international research groups. After across-site harmonization with ComBat, we compared 493 patients with functional motor disorder and functional seizures with 564 healthy control participants. Euler numbers were included to account for head motion.</p><p><strong>Results: </strong>The FND cohort showed reduced cortical thickness in the bilateral superior frontal gyri (left d = 0.22, right d = 0.21) and sulci (d = 0.22 and 0.23), bilateral superior precentral sulcus (d = 0.22 and 0.26), right precentral gyrus (d = 0.25), right paracentral gyrus and sulcus (d = 0.23), right cuneus (d = 0.23), and right inferior opercular gyrus (d = 0.21); we also found reduced left postcentral gyrus surface area (d = 0.25) and right hippocampal volume (d = 0.22). No regions were different in relative surface area. There were no associations between morphometrics and illness duration or lifetime history of depression or anxiety. Differences between motor and seizure variants were not identified.</p><p><strong>Conclusions: </strong>This large mega-analysis suggests subtle morphometric differences, particularly in prefrontal and motor regions. This may represent predisposing vulnerabilities, compensatory mechanisms, or FND-specific alterations. Improved neuropsychiatric characterization of FND research cohorts will help further contextualize the biological relevance of structural alterations.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418295","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":"Topological Data Analysis Communities Reveal Gene-Environment-Brain Subtypes of Major Depression in UK Biobank and Multisite Cohorts.","authors":"Emma Tassi, Alessandro Pigoni, Federica Colombo, Lidia Fortaner-Uyà, Cristina Colombo, Anna Maria Bianchi, Francesco Benedetti, Chiara Fabbri, Alessandro Serretti, Benedetta Vai, Paolo Brambilla, Eleonora Maggioni","doi":"10.1016/j.biopsych.2026.06.030","DOIUrl":"10.1016/j.biopsych.2026.06.030","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) exhibits substantial clinical heterogeneity, which complicates prognosis and treatment. Characterizing MDD subtypes could enhance personalized approaches. We developed a topological data analysis (TDA) framework with graph-based community detection to identify patient subgroups using multimodal data.</p><p><strong>Methods: </strong>We implemented a TDA pipeline in participants with MDD from the UK Biobank, with genetic-environmental (G-E, 20,715 subjects) and genetic-environmental-neuroimaging (G-E-I, 3044 subjects) data. We systematically compared genetic, environmental, and neuroimaging features, alone and combined, to stratify individuals with MDD across 18 health-related outcomes. For each outcome's best-performing feature set, a novel feature-ranking approach identified features driving graph construction and community-based outcome differentiation. Cross-cohort validation through selective, heterogeneous replication utilized 2 independent datasets: the GSRD (European Group for the Study of Resistant Depression) (G-E data, 1017 subjects) and Hospital San Raffaele (HSR) (G-E and imaging data, 71-87 subjects).</p><p><strong>Results: </strong>The G-E combination demonstrated superior stratification performance for 13 outcomes, including treatment-resistant depression (TRD), symptom subtypes, and suicidal phenotypes. Community profiling revealed distinct patterns: trauma-stress exposures were linked to TRD and episode severity, whereas substance-behavioral profiles were associated with anxious symptoms. Environmental factors primarily determined most health-related outcomes, whereas neuroimaging features best discriminated medical comorbidities. Partial replication was observed for G-E sets in the GSRD (self-harm behavior, anxious features) and preliminary imaging-based replication in the HSR (vascular problems), with limited statistical power for imaging analyses. Environmental stress-related top-ranked features were consistent across cohorts.</p><p><strong>Conclusions: </strong>TDA successfully identified relevant MDD subgroups with domain-specific multimodal contributions. These findings underscore the value of multimodal integration for comprehensive health-related outcome stratification, with modalities contributing selectively to specific outcome domains. TDA-based community detection is a promising framework for MDD stratification and precision medicine.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418254","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":"Human Cellular Models of Autism and Related Conditions.","authors":"Sudha R Guttikonda, Christopher D Makinson","doi":"10.1016/j.biopsych.2026.07.003","DOIUrl":"10.1016/j.biopsych.2026.07.003","url":null,"abstract":"<p><p>Human cellular models are enabling the in vitro study of the complex molecular and cellular mechanisms underlying autism spectrum disorder (ASD). Human embryonic stem cell- and human induced pluripotent stem cell (hiPSC)-derived models have progressed from investigating single genes to multiplexed approaches that have allowed the study of several ASD risk genes in parallel, which have expanded our understanding of how coding and noncoding genetic variants shape cellular and molecular phenotypes in ASD. Additionally, these models have identified several convergent pathogenic mechanisms in ASD, including dysregulated neurogenesis, altered cell-type specification (such as defects in glutamatergic neurons and expansion of GABAergic [gamma-aminobutyric acidergic] neurons), and disrupted synaptic activity. Common molecular principles are also emerging, including dysregulation of chromatin, WNT signaling, and mTOR (mechanistic target of rapamycin) signaling. hiPSC models of ASD have also been used to evaluate the effect of several U.S. Food and Drug Administration-approved therapeutic compounds on early human neural development, such as mTOR inhibitors, some of which are currently in clinical trials for ASD-related conditions. Although human cellular models have limitations, their unique strength is the ability to reveal early developmental pathophysiology and the potential to correlate in vitro phenotypes with the clinical features of patient donors. Here, we examine how human cellular models have advanced basic and translational research in ASD and identify key cellular and molecular convergent phenotypes that have emerged.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418212","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}