Biological Psychiatry最新文献

{"title":"Computational Phenotyping of Aberrant Belief Updating in Individuals With Schizotypal Traits and Schizophrenia","authors":"Nace Mikus ,&nbsp;Claus Lamm ,&nbsp;Christoph Mathys","doi":"10.1016/j.biopsych.2024.08.021","DOIUrl":"10.1016/j.biopsych.2024.08.021","url":null,"abstract":"<div><h3>Background</h3><div>Psychotic experiences are thought to emerge from various interrelated patterns of disrupted belief updating, such as overestimating the reliability of sensory information and misjudging task volatility, yet these substrates have never been jointly addressed under one computational framework, and it is not clear to what degree they reflect trait-like computational patterns.</div></div><div><h3>Methods</h3><div>We introduce a novel hierarchical Bayesian model that describes how individuals simultaneously update their beliefs about the task volatility and noise in observation. We applied this model to data from a modified predictive inference task in a test-retest study with healthy volunteers (<em>N</em> = 45, 4 sessions) and examined the relationship between model parameters and schizotypal traits in a larger online sample (<em>N</em> = 437) and in a cohort of patients with schizophrenia (<em>N</em> = 100).</div></div><div><h3>Results</h3><div>The interclass correlations were moderate to high for model parameters and excellent for averaged belief trajectories and precision-weighted learning rates estimated through hierarchical Bayesian inference. We found that uncertainty about the task volatility was related to schizotypal traits and to positive symptoms in patients, when learning to gain rewards. In contrast, negative symptoms in patients were associated with more rigid beliefs about observational noise, when learning to avoid losses.</div></div><div><h3>Conclusions</h3><div>These findings suggest that individuals with schizotypal traits across the psychosis continuum are less likely to learn or use higher-order statistical regularities of the environment and showcase the potential of clinically relevant computational phenotypes for differentiating symptom groups in a transdiagnostic manner.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 2","pages":"Pages 188-197"},"PeriodicalIF":9.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103996","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":"Brainwide Anatomical Connectivity and Prediction of Longitudinal Outcomes in Antipsychotic-Naïve First-Episode Psychosis","authors":"Sidhant Chopra ,&nbsp;Priscila T. Levi ,&nbsp;Alexander Holmes ,&nbsp;Edwina R. Orchard ,&nbsp;Ashlea Segal ,&nbsp;Shona M. Francey ,&nbsp;Brian O’Donoghue ,&nbsp;Vanessa L. Cropley ,&nbsp;Barnaby Nelson ,&nbsp;Jessica Graham ,&nbsp;Lara Baldwin ,&nbsp;Hok Pan Yuen ,&nbsp;Kelly Allott ,&nbsp;Mario Alvarez-Jimenez ,&nbsp;Susy Harrigan ,&nbsp;Christos Pantelis ,&nbsp;Stephen J. Wood ,&nbsp;Patrick McGorry ,&nbsp;Alex Fornito","doi":"10.1016/j.biopsych.2024.07.016","DOIUrl":"10.1016/j.biopsych.2024.07.016","url":null,"abstract":"<div><h3>Background</h3><div>Disruptions of axonal connectivity are thought to be a core pathophysiological feature of psychotic illness, but whether they are present early in the illness, prior to antipsychotic exposure, and whether they can predict clinical outcome remain unknown.</div></div><div><h3>Methods</h3><div>We acquired diffusion-weighted magnetic resonance images to map structural connectivity between each pair of 319 parcellated brain regions in 61 antipsychotic-naïve individuals with first-episode psychosis (15–25 years, 46% female) and a demographically matched sample of 27 control participants. Clinical follow-up data were also acquired in patients 3 and 12 months after the scan. We used connectome-wide analyses to map disruptions of inter-regional pairwise connectivity and connectome-based predictive modeling to predict longitudinal change in symptoms and functioning.</div></div><div><h3>Results</h3><div>Individuals with first-episode psychosis showed disrupted connectivity in a brainwide network linking all brain regions compared with controls (familywise error–corrected <em>p</em> = .03). Baseline structural connectivity significantly predicted change in functioning over 12 months (<em>r</em> = 0.44, familywise error–corrected <em>p</em> = .041), such that lower connectivity within fronto-striato-thalamic systems predicted worse functional outcomes.</div></div><div><h3>Conclusions</h3><div>Brainwide reductions of structural connectivity exist during the early stages of psychotic illness and cannot be attributed to antipsychotic medication. Moreover, baseline measures of structural connectivity can predict change in patient functional outcomes up to 1 year after engagement with treatment services.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 2","pages":"Pages 157-166"},"PeriodicalIF":9.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787179","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":"Subscribers Page","authors":"","doi":"10.1016/S0006-3223(24)01740-2","DOIUrl":"10.1016/S0006-3223(24)01740-2","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 2","pages":"Page A2"},"PeriodicalIF":9.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143172660","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":"Finding the Right Dose: NMDA Receptor–Modulating Treatments for Cognitive and Plasticity Deficits in Schizophrenia and the Role of Pharmacodynamic Target Engagement","authors":"Pejman Sehatpour,&nbsp;Joshua T. Kantrowitz","doi":"10.1016/j.biopsych.2024.08.019","DOIUrl":"10.1016/j.biopsych.2024.08.019","url":null,"abstract":"<div><div>Cognitive impairment associated with schizophrenia (CIAS) and related deficits in learning (plasticity) are among the leading causes of disability in schizophrenia. Despite this, there are no Food and Drug Administration–approved treatments for CIAS, and the development of treatments has been limited by numerous phase 2/3 failures of compounds that showed initial promise in small-scale studies. NMDA-type glutamate receptors (NMDARs) have been proposed to play an important role in schizophrenia; moreover, the NMDAR has a well-characterized role in cognition, learning, and neuroplasticity. We review previously published clinical trials in CIAS that focused on NMDAR modulator treatments, focusing on published and recent developments of the use of novel NMDAR-modulating treatments for CIAS both alone and combined with plasticity/learning paradigms to enhance learning. We use this discussion of previous studies to highlight the importance of incorporating pharmacodynamic target engagement biomarkers early in treatment development, which can help predict which compounds will succeed or fail in phase 3. A range of direct and indirect NMDAR modulators are covered, including D-serine, D-cycloserine, memantine, and glycine and first-generation glycine transport inhibitors (e.g., sarcosine and bitopertin), as well as recent positive studies of iclepertin, a novel glycine transport inhibitor, and luvadaxistat, a D-amino acid oxidase inhibitor that increases brain D-serine levels, and indirect noninvasive brain stimulation NMDAR-modulating treatments. Several examples of successful use of pharmacodynamic target engagement biomarkers for dose/drug discovery are emphasized, including the mismatch negativity, auditory steady state, and time-frequency event-related potential approaches.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 2","pages":"Pages 128-138"},"PeriodicalIF":9.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103997","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(24)01798-0","DOIUrl":"10.1016/S0006-3223(24)01798-0","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 4","pages":"Page A1"},"PeriodicalIF":9.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143137534","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(24)01743-8","DOIUrl":"10.1016/S0006-3223(24)01743-8","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 2","pages":"Pages A5-A10"},"PeriodicalIF":9.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143172658","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":"Sex Differences in the Striatal Contributions to Longitudinal Fine Motor Development in Autistic Children.","authors":"Olivia Surgent, Derek S Andrews, Joshua K Lee, Joseph Boyle, Andrew Dakopolos, Meghan Miller, Sally Ozonoff, Sally J Rogers, Marjorie Solomon, David G Amaral, Christine Wu Nordahl","doi":"10.1016/j.biopsych.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.005","url":null,"abstract":"<p><strong>Background: </strong>Fine motor challenges are prevalent in autistic populations. However, little is known about their neurobiological underpinnings or how their related neural mechanisms are influenced by sex. The dorsal striatum, comprised of the caudate nucleus and putamen, is associated with motor learning and control and may hold critical information. We investigated how autism diagnosis and sex assigned at birth influence associations between the dorsal striatum and fine motor development in autistic and non-autistic children.</p><p><strong>Methods: </strong>We used multimodal assessment of striatal structures (volume and cortico-striatal white matter microstructure) and longitudinal assessment of fine motor skills, first at approximately 3 years of age (Time 1) and again 2-3 years later (Follow-up). Fine motor and magnetic resonance imaging (T1 and diffusion) data were collected at Time 1 from 356 children (234 autistic; 128 female) and at Follow-up from 195 children (113 autistic; 76 female).</p><p><strong>Results: </strong>At Time 1, associations among fine motor skills, putamen volume, and sensorimotor-striatal fractional anisotropy (sensorimotor-affiliated dorsal striatal structures) were different in autistic boys compared to autistic girls and were not significant for non-autistic children. Further, Time 1 sensorimotor-striatal and prefrontal-striatal microstructure predicted fine motor development for autistic girls but not boys.</p><p><strong>Conclusions: </strong>Sensorimotor-affiliated dorsal striatum structures may contribute to concurrent motor ability and predict fine motor improvement during critical windows of development in a sex-specific and diagnosis-dependent way. Moreover, the dorsal striatum may play a key role in the distinct neural mechanisms underlying motor challenges in autistic males and females.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999488","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":"Bipolar Disorder and Artistic Temperament: Mechanisms Linking Creativity and Bipolar Disorder.","authors":"Mikael Landén","doi":"10.1016/j.biopsych.2025.01.003","DOIUrl":"10.1016/j.biopsych.2025.01.003","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969546","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":"Personalized theta-burst stimulation enhances social skills in young minimally verbal children with autism: a double-blind randomized controlled trial.","authors":"Jinming Xiao, Yating Ming, Lei Li, Xinyue Huang, Yuanyue Zhou, Jianjun Ou, Juan Kou, Rui Feng, Rui Ma, Qingyu Zheng, Xiaolong Shan, Yao Meng, Wei Liao, Yingli Zhang, Ting Wang, Yangying Kuang, Jing Cao, Shijun Li, Hua Lai, Jia Chen, Qi Wang, Xiaoli Dong, Xiaodong Kang, Huafu Chen, Vinod Menon, Xujun Duan","doi":"10.1016/j.biopsych.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.002","url":null,"abstract":"<p><strong>Background: </strong>Minimally verbal children with autism are understudied and lack effective treatment options. Personalized continuous theta-burst stimulation (cTBS) targeting the amygdala and its circuitry may be a potential therapeutic approach for this population.</p><p><strong>Methods: </strong>In a double-blind randomized controlled trial, minimally verbal children with autism (ages 2-8 years) received 4 weeks of cTBS. An amygdala-optimized functional connectivity (AOFC) group (N=23) received personalized stimulation targeting a left dorsolateral prefrontal cortex site functionally connected with the amygdala. A non-optimized (NO) control group (N=21) received stimulation at a standard prefrontal site. We assessed changes in Autism Diagnostic Observation Schedule scores, amygdala volume, spontaneous neural activity, and functional connectivity.</p><p><strong>Results: </strong>Personalized AOFC-guided cTBS improved social and communication skills with an effect size twice that of the NO group (Cohen's d = 0.55 vs. 0.24). The AOFC group showed greater reductions in amygdala volume, spontaneous neural activity, and hyper-connectivity. Network-level amygdala connectivity changes with default mode, frontoparietal, and dorsal attention networks were correlated with clinical improvements. Field mapping analysis revealed that greater electric field overlap between standard and optimized targets predicted better treatment outcomes.</p><p><strong>Conclusions: </strong>Personalized AOFC-guided cTBS enhanced social skills and communication in minimally verbal children with autism by modulating amygdala structure and connectivity. Changes in amygdala network connectivity predicted clinical improvements, suggesting a mechanistic link between neural circuit plasticity and behavioral outcomes. These findings demonstrate the potential of precision-targeted neuromodulation in addressing a critical gap in autism treatment for this understudied population.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969548","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":"Focused Ultrasound Neuromodulation: Exploring a Novel Treatment for Severe Opioid Use Disorder.","authors":"Ali Rezai, Daisy G Y Thompson-Lake, Pierre-François D'Haese, Nathalie Meyer, Manish Ranjan, Daniel Farmer, Victor Finomore, Jennifer L Marton, Sally Hodder, Jeffrey Carpenter, Aniruddha Bhagwat, James Berry, Padma Tirumalai, Geoffrey Adams, Tasneem Arsiwala, Olaf Blanke, James J Mahoney","doi":"10.1016/j.biopsych.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.001","url":null,"abstract":"<p><strong>Background: </strong>Opioid use disorder remains a critical healthcare challenge as current therapeutic strategies have limitations resulting in high recurrence and deaths. We evaluated safety and feasibility of focused ultrasound (FUS) neuromodulation to reduce substance cravings and use in severe opioid- and co-occurring substance use disorders.</p><p><strong>Methods: </strong>This prospective, open-label, single-arm study enrolled 8 participants with severe, primary opioid use disorder with co-occurring substance use. Participants received a 20-minute session of low-intensity FUS (220 kHz) neuromodulation targeting the bilateral nucleus accumbens (NAc) with follow-up for 90-days. Outcome measures included safety, tolerability, feasibility, and effects of FUS neuromodulation by assessment of adverse events, substance craving, substance use (self-report, urine toxicology), mood, neurologic examinations, and anatomic and functional MRI, at 1-, 7-, 30-, 60, and 90- day post-FUS.</p><p><strong>Results: </strong>No serious device-related adverse events or imaging abnormalities were observed. Following FUS, participants demonstrated immediate (p<.002) and sustained (p<.0001; mean 91%) reduction in cue-induced opioid craving with median rating on scale from 0-10: 6.9 (pre-FUS) vs. 0.6 (90-day post-FUS). Craving reductions were similar for other illicit substances (e.g., methamphetamine (p<.002), cocaine (p<.02)). Decreases in opioid and co-occurring substance use were confirmed by urine toxicology. Seven participants remained abstinent at 30-days; 5 remained abstinent throughout 90-days post-FUS. Resting-state functional MRI demonstrated decrease in connectivity from the NAc to reward and cognitive regions post-FUS.</p><p><strong>Conclusions: </strong>NAc FUS neuromodulation is safe and a potential adjunctive treatment for reducing drug cravings and use in individuals with severe opioid- and co-occurring substance use disorders. Larger, sham-controlled, randomized studies are warranted.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969547","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}