{"title":"Biological mechanisms of sleep/wake related function.","authors":"Greene Robert","doi":"10.1016/j.biopsych.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.002","url":null,"abstract":"<p><p>Animals oscillate between sleep and wake periods characterized by foraging for food and avoiding danger, with a relatively high level of arousal during waking, and by relative absence of movement and decreased level of arousal during sleep. In the brain, at the cellular level, waking involves energy efficient oxidative phosphorylation that can conserve metabolites, whereas during sleep, energy and metabolites are utilized to support protein anabolism and turnover. At the intercellular level this bias in metabolism can facilitate sleep-dependent glutamate synaptic reorganization by downscaling synaptic strength and enhancement of metaplastic potentiating plasticity. The dual focus of this review is on the molecules and genetics in the intracellular pathways controlling the functionally permissive state of sleep and the functional outcomes of sleep. These sleep-related functional outcomes require MEF2c-dependent transcriptional changes targeting genes regulating glutamate synapses. The same genes are enriched for known risk factor genes for autism spectrum disorder consistent with an interaction of sleep and autism.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282247","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}
Victoria Sharpe, Michael Mackinley, Samer Nour Eddine, Lin Wang, Lena Palaniyappan, Gina R Kuperberg
{"title":"Selective insensitivity to global vs. local linguistic context in speech produced by patients with untreated psychosis and positive thought disorder.","authors":"Victoria Sharpe, Michael Mackinley, Samer Nour Eddine, Lin Wang, Lena Palaniyappan, Gina R Kuperberg","doi":"10.1016/j.biopsych.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.001","url":null,"abstract":"<p><strong>Background: </strong>Early psychopathologists proposed that certain features of positive thought disorder, the disorganized language output produced by some people with schizophrenia, suggest an insensitivity to global, relative to local, discourse context. This idea has received support from carefully controlled psycholinguistic studies in language comprehension. In language production, researchers have so far remained reliant on subjective qualitative rating scales to assess and understand speech disorganization. Now, however, recent advances in large language models mean that it is possible to quantify sensitivity to global and local context objectively by probing lexical probability (the predictability of a word given its preceding context) during natural language production.</p><p><strong>Methods: </strong>For each word in speech produced by 60 first-episode psychosis patients and 35 healthy, demographically-matched controls, we extracted lexical probabilities from GPT-3 based on contexts that ranged from very local- a single preceding word: P(Wn | Wn-1)-to global-up to 50 preceding words: P(Wn|Wn-50, Wn-49, …, Wn-1).</p><p><strong>Results: </strong>We show that disorganized speech is characterized by disproportionate insensitivity to global, versus local, linguistic context. Critically, this global-versus-local insensitivity selectively predicted clinical ratings of positive thought disorder, above and beyond overall symptom severity. There was no evidence of a relationship with negative thought disorder (impoverishment).</p><p><strong>Conclusions: </strong>We provide an automated, interpretable measure that can potentially be used to quantify speech disorganization in schizophrenia. Our findings directly link the clinical phenomenology of thought disorder to neurocognitive constructs that are grounded in psycholinguistic theory and neurobiology.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282248","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}
Louise Stiernman, Manon Dubol, Erika Comasco, Maja Johansson, Lars Stiernman, Marie Bixo
{"title":"Emotion generation and regulation in premenstrual dysphoric disorder: dysregulation of large-scale brain networks across the menstrual cycle.","authors":"Louise Stiernman, Manon Dubol, Erika Comasco, Maja Johansson, Lars Stiernman, Marie Bixo","doi":"10.1016/j.biopsych.2025.05.025","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.05.025","url":null,"abstract":"<p><strong>Background: </strong>Emotion regulation deficits have been highlighted as a transdiagnostic feature of multiple psychiatric disorders, including premenstrual dysphoric disorder (PMDD). In this study, we hypothesize that deficient prefrontal \"top-down\" regulation of key nodes of the salience network (SN) is a characteristic of PMDD, driven by increased levels of progesterone-derived neuroactive steroids.</p><p><strong>Methods: </strong>Functional magnetic resonance imaging (fMRI) was used to investigate menstrual-cycle related variations in brain activity and connectivity during two emotional tasks (emotion generation and regulation) in 29 women with PMDD and 27 controls. We also examined whether differential brain activation between groups is related to serum levels of progesterone-derived neuroactive steroids and premenstrual symptom severity.</p><p><strong>Results: </strong>Women with PMDD showed increased reactivity in key nodes of the SN and - at subthreshold level - in the default mode network (DMN) during the luteal phase when passively viewing negative emotional stimuli. Intriguingly, SN hyperactivity in PMDD patients was apparent also during the follicular phase and related to premenstrual symptom severity. PMDD and control women had similar network connectivity patterns and activity in regions associated with the conscious control of emotion in PMDD. No link to progesterone-derived neuroactive steroids was found.</p><p><strong>Conclusions: </strong>Multiple network aberrations during the luteal phase may explain the development of mood symptoms in the luteal phase. Furthermore, higher baseline (follicular) SN activity may render PMDD women more susceptible to severe mood symptoms in response to hormonal fluctuations. What drives increased SN activity in the follicular phase is unknown, but innate and neuroplastic mechanisms are proposed.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246241","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}
Carolyn M Amir, Dara G Ghahremani, Sarah E Chang, Ziva D Cooper, Carrie E Bearden
{"title":"Altered neurobehavioral reward response predicts psychotic-like experiences in youth exposed to cannabis prenatally.","authors":"Carolyn M Amir, Dara G Ghahremani, Sarah E Chang, Ziva D Cooper, Carrie E Bearden","doi":"10.1016/j.biopsych.2025.05.019","DOIUrl":"10.1016/j.biopsych.2025.05.019","url":null,"abstract":"<p><strong>Background: </strong>Rates of prenatal cannabis exposure (PCE) are rising with increasingly permissive legislation, which may be a risk factor for psychosis. Disrupted reward-related neural circuitry may underlie this relationship. We aim to elucidate neural mechanisms involved in the association between PCE and youth-onset psychotic-like experiences (PLEs) by probing correlates of reward anticipation, a neurobehavioral marker of endocannabinoid-mediated dopaminergic function.</p><p><strong>Methods: </strong>This longitudinal, prospective study analyzed task-related functional neuroimaging data from baseline (n=11,368), 2-year follow-up (n=7,928), and 4-year follow-up (n=2,982) of the ongoing Adolescent Brain and Cognitive Development (ABCD) Study, which recruited children aged 9 to 10 years old at baseline from 22 sites across the United States.</p><p><strong>Results: </strong>PCE (n=652 exposed youth) is longitudinally associated with PLEs. Blunted neural response to reward anticipation is associated with PLEs, with stronger effects observed in PCE youth (all |β|> 0.5; false discovery rate [FDR]-corrected P < .05). This baseline hypoactivation predicts PLEs in middle adolescence (β=-.004; FDR-corrected P < .05) and mediates the relationship between PCE and PLEs. Dampened behavioral reward sensitivity is associated with PLEs across visits (|β| = .21; FDR-corrected P < .001). PLEs are positively associated with trait-level measures of reward motivation and impulsivity, with stronger effects for PCE youth (all |β| > 0.1; all FDR-corrected P < .05).</p><p><strong>Conclusions: </strong>Blunted striatal activation may serve as a biomarker for disrupted reward processing and increased psychosis risk during development. PCE may affect childhood behaviors and traits related to altered reward sensitivity.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224185","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}
Gayle M Wittenberg, Rachel Upthegrove, Wayne C Drevets, Husseini K Manji
{"title":"The Future of Immunotherapies for Mental Illness: A Precision Medicine Perspective.","authors":"Gayle M Wittenberg, Rachel Upthegrove, Wayne C Drevets, Husseini K Manji","doi":"10.1016/j.biopsych.2025.05.021","DOIUrl":"10.1016/j.biopsych.2025.05.021","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224186","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}
Kevin S. O’Connell , Rolf Adolfsson , Till F.M. Andlauer , Michael Bauer , Bernhaud Baune , Joanna M. Biernacka , Bernardo Carpiniello , Sven Cichon , Nick Craddock , Alfredo B. Cuellar-Barboza , Udo Dannlowski , Franziska Degenhardt , Dimitris Dikeos , Panagiotis Ferentinos , Andreas J. Forstner , Mark A. Frye , Janice M. Fullerton , Maria Grigoroiu-Serbanescu , José Guzman-Parra , Lisa Jones , Ole A. Andreassen
{"title":"New Genomics Discoveries Across the Bipolar Disorder Spectrum Implicate Neurobiological and Developmental Pathways","authors":"Kevin S. O’Connell , Rolf Adolfsson , Till F.M. Andlauer , Michael Bauer , Bernhaud Baune , Joanna M. Biernacka , Bernardo Carpiniello , Sven Cichon , Nick Craddock , Alfredo B. Cuellar-Barboza , Udo Dannlowski , Franziska Degenhardt , Dimitris Dikeos , Panagiotis Ferentinos , Andreas J. Forstner , Mark A. Frye , Janice M. Fullerton , Maria Grigoroiu-Serbanescu , José Guzman-Parra , Lisa Jones , Ole A. Andreassen","doi":"10.1016/j.biopsych.2025.05.020","DOIUrl":"10.1016/j.biopsych.2025.05.020","url":null,"abstract":"<div><div>Bipolar disorder (BD) is a highly heritable mental disorder that affects millions of people worldwide. Our understanding of the genetic etiology and biological processes that underlie BD have greatly increased in recent years. Extensive progress has been made in identifying common variant signals for BD, and the polygenic score from the latest genome-wide association study (GWAS) may provide some clinical utility if combined with other risk factors for BD. The role of rare variation in BD remains to be determined, although genes annotated to common variant loci are shown to be enriched for rare variation. BD subtypes have been shown to differ in their genetic architecture, and as such, genetic studies across the subtypes of the BD spectrum will identify subtype-specific signals and reveal subtype-specific biological mechanisms. Despite this, subtype-specific GWAS sample sizes have not increased at the same rate as BD cases, and more concerted efforts are required to obtain this information for participants included in future BD GWASs. Moreover, assessment of culture, geography, and other systematic differences that may impact patient assessment will be necessary to ensure accurate inclusion of diverse ancestral groups and global representation in genetic studies of BD moving forward.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 4","pages":"Pages 302-310"},"PeriodicalIF":9.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207546","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":"Identifying Transdiagnostic Aggression Networks: The Role of Lesion Studies","authors":"Karim Ibrahim","doi":"10.1016/j.biopsych.2025.04.006","DOIUrl":"10.1016/j.biopsych.2025.04.006","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 12","pages":"Pages 1113-1115"},"PeriodicalIF":9.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169846","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}