Biological Psychiatry最新文献

{"title":"Histone deacetylase 5 in prelimbic prefrontal cortex limits context-associated cocaine seeking.","authors":"Sarah M Barry, Jessica Huebschman, Derek M Devries, Lauren M McCue, Evgeny Tsvetkov, Rose Marie Akiki, Caroline Limbaker, Ethan M Anderson, Daniel J Wood, Benjamin M Siemsen, Stefano Berto, Michael D Scofield, Makoto Taniguchi, Rachel D Penrod, Christopher W Cowan","doi":"10.1016/j.biopsych.2025.06.027","DOIUrl":"10.1016/j.biopsych.2025.06.027","url":null,"abstract":"<p><strong>Background: </strong>Repeated cocaine use produces neuroadaptations that support drug craving and relapse in substance use disorders (SUDs). Powerful associations formed with drug-use environments can promote a return to active drug use in SUD patients, but the molecular mechanisms that control the formation of these prepotent drug-context associations remain unclear.</p><p><strong>Methods: </strong>In an animal model of intravenous cocaine self-administration (SA) model, we used male Sprague-Dawley rats to examine the role of histone deacetylase 5 (HDAC5) in the prelimbic (PrL) and infralimbic (IL) cortices in context-associated drug seeking. To this end, we employed viral molecular tools, chemogenetics, RNA-sequencing, electrophysiology, and immunohistochemistry.</p><p><strong>Results: </strong>In the PrL, reduction of endogenous HDAC5 augmented context-associated, but not cue- or drug prime-reinstated cocaine seeking, whereas overexpression of HDAC5 in PrL, but not IL, reduced context-associated cocaine seeking, but had no effects on sucrose seeking. In contrast, PrL HDAC5 overexpression following acquisition had no effects on future cocaine seeking. We found that HDAC5 and cocaine SA altered expression of numerous PrL genes, including many synapse-associated genes. HDAC5 significantly increased inhibitory synaptic transmission onto PrL deep-layer pyramidal neurons, and reduced the induction of FOS-positive neurons in the cocaine SA environment.</p><p><strong>Conclusions: </strong>Our findings reveal an essential and selective role for PrL HDAC5 to limit associations formed in cocaine, but not sucrose, SA environments, and that it alters the PrL excitatory/inhibitory balance, possibly through epigenetic regulation of synaptic genes. These results further position HDAC5 as a key factor regulating reward-circuit neuroadaptations that underlie common relapse triggers in SUD.</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":"144599198","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":"Obesity during pregnancy and deficits in offspring neurobehavioral flexibility: The CONFINE Model.","authors":"John E Krzeczkowski, Neda Mortaji, Ryan J Van Lieshout","doi":"10.1016/j.biopsych.2025.06.032","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.032","url":null,"abstract":"<p><p>Exposure to prenatal obesity is associated with to multiple psychiatric and cognitive problems in children. However, it is unclear how and why these children are at risk for such a wide range of difficulties. Prenatal obesity may alter fetal neurodevelopment in ways that shape broad traits that underly the etiology and symptomatology of the multiple problems observed in children. Novel theoretical frameworks that identify these traits are critical to developing a more complete understanding of how and why prenatal obesity adversely impacts children's psychiatric and cognitive functioning. In this review, we propose the CONFINE model (Confined Offspring Neurobehavioral Flexibility following INtrauterine obesity Exposure) which posits that prenatal exposure to maternal obesity leads to neurobehavioral flexibility deficits in children. It is argued that prenatal obesity alters the fetal: i) hypothalamic energy-balance system in ways that constrain child behavior toward food seeking/consumption; ii) central reward systems (μ-opioid and mesocorticolimbic dopamine system), making it difficult for children to disengage from reward seeking/consuming behaviors, and iii) higher-order salience and cognitive control networks, constraining children's attention toward reward cues, and problems with altering goal-directed behaviors. Together, these changes contribute to neurobehavioral flexibility deficits which, depending on postnatal conditions, may increase children's risk for multiple psychiatric and cognitive problems. The CONFINE model aims to integrate the effects of prenatal obesity on children from neural systems to observed behaviors and enable researchers to develop testable hypotheses to gain a more comprehensive understanding of the associations, mechanisms, and risk trajectories of children prenatally exposed to obesity.</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":"144599201","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":"How does altered function of the hippocampus contribute to the development of psychosis?","authors":"Valentina Mancini, Farnaz Delavari, Tae-Yeon Eom, Stanislav S Zakharenko, Eric Schmitt, Stephan Eliez","doi":"10.1016/j.biopsych.2025.06.022","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.022","url":null,"abstract":"<p><p>This review explores the critical role of hippocampal dysfunction in the pathophysiology of psychosis, focusing on translational insights from 22q11.2 deletion syndrome (22q11DS). Converging evidence indicates that individuals with 22q11DS, one of the highest genetic risk factors for schizophrenia, exhibit a shared neurobiological vulnerability with idiopathic psychosis, characterized by cognitive decline and atypical brain development, particularly within the hippocampus. Here we explore translational evidence for hippocampal dysfunction in humans with 22q11DS and the homologous mouse models at different scales. At the neuronal level, deficits include impaired neural migration, reduced dendritic spine density of pyramidal neurons, and decreased neurogenesis. These deficits contribute to circuit-level alterations such as altered glutamatergic transmission and impaired long-term potentiation, leading to memory impairment. Moreover, hypoexcitability of parvalbumin-positive interneurons (PVI) disrupts gamma-band oscillations in the hippocampus. At the network level, reduced hippocampal-prefrontal synchrony and hypoconnectivity are observed in both mouse models and humans with 22q11DS. These findings support a model in which neurodevelopmental deficits in neural migration result in circuit dysfunction, which impacts large-scale neural dynamics and cognition. Crucially, hippocampal-prefrontal hypoconnectivity and imbalances between excitatory and inhibitory neurotransmitters are exacerbated in 22q11DS carriers with psychotic symptoms. Studies targeting dendritic spine density and PVI function in 22q11DS mouse models show potential for reversing neural and cognitive deficits, suggesting new therapeutic strategies. The effectiveness of these treatments varies with age, highlighting the need to identify critical developmental windows for intervention. In conclusion, this review emphasizes the hippocampus as a target for understanding and treating psychotic disorders.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582967","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":"Guided by Expectations: Overweighted Semantic Priors in Schizotypy and their Links to Glutamate.","authors":"Franziska Knolle, Elisabeth F Sterner, Verena F Demler, Lucy J MacGregor, Christoph Mathys","doi":"10.1016/j.biopsych.2025.06.025","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.025","url":null,"abstract":"<p><strong>Background: </strong>An imbalance in the weighting of prior beliefs and sensory evidence is thought to contribute to the development of psychotic symptoms, such as hallucinations and delusions. We investigated (1) how much individuals with schizotypal traits, a subclinical expression of psychosis-proneness, use high-level semantic priors and sensory evidence to understand noise-degraded language; (2) whether an imbalance would potentially result in task-based hallucinations - perceptions that match expectations but not the input; and finally (2) whether an potential imbalance was linked to altered levels of cortical glutamate.</p><p><strong>Methods: </strong>In a language comprehension task, we simultaneously manipulated semantic predictability, sensory degradation and surprisal to estimate the prior weight using a Bayesian Belief updating model. We conducted two studies. Study 1 (n=109) tested the language comprehension task behaviourally; study 2 (n=55) was used to replicate the findings of study 1; but was furthermore combined with 1H-Magnetresonance spectroscopy to assess cortical levels of glutamate.</p><p><strong>Results: </strong>Study 1 showed that high-level priors were overweighted with increasing schizotypy providing a potential explanation for the increased number of task-based hallucination observed in the same individuals. Importantly, study 2 (n=55), replicating the results of study 1, revealed that an overweighting of priors was associated with increased cingulate glutamate, providing a neurobiological basis for over-reliance on top-down predictions.</p><p><strong>Conclusion: </strong>These results offer a mechanistic and neurobiological understanding of how predictive coding alterations contribute to symptom development along the psychosis spectrum.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582966","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":"Impaired Global and Regional Peak Systolic Strain and Myocardial Work in Young Adults With Bipolar Disorder.","authors":"Cheng-Yi Hsiao, Tsung-Han Hsieh, Hsin-Yi Lai, Kevin Li-Chun Hsieh, Kuo-Hsuan Chung, Yun-Ru Liu, Shang-Ying Tsai, Pao-Huan Chen","doi":"10.1016/j.biopsych.2025.06.021","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.021","url":null,"abstract":"<p><strong>Background: </strong>Patients with bipolar disorder (BD) have a high risk of heart failure. Thus, cardiac dysfunction in these patients must be detected early to prevent heart failure. Herein, we evaluated cardiac systolic function in young adults with BD by using novel measures-global and regional peak systolic strain and myocardial work, which were measured using 2-dimensional speckle-tracking echocardiography and the American Heart Association 17-segment polar map.</p><p><strong>Methods: </strong>This study included 160 individuals, comprising 106 patients with BD and 54 individuals without psychiatric disorders (age: 20 to 45 y), who underwent 2-dimensional speckle-tracking echocardiography. Left ventricular (LV) peak systolic strain and myocardial work were measured following the guidelines and technique recommendations of the American Society of Echocardiography and European Association of Cardiovascular Imaging.</p><p><strong>Results: </strong>For individuals with preserved ejection fraction, the BD group exhibited worse performances on LV global longitudinal strain (Cohen's d = 1.08; P < .001), LV global work index (Cohen's d = 0.49; P = .019), LV global constructive work (Cohen's d = 0.81; P < .001), and LV global wasted work (Cohen's d = 0.11; P = .048) than did the group without psychiatric disorders. Peak systolic strain and myocardial work were impaired in multiple LV segments, which involved perfusion territories of 3 major coronary arteries.</p><p><strong>Conclusions: </strong>Our findings suggest that peak systolic strain and myocardial work are extensively impaired across LV segments in young adults with BD. Future studies should explore the pathways that link coronary vascular dysfunction to abnormal myocardial contractility in patients with BD.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582968","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":"Changes in Model-Based and Model-Free Control Prospectively Predict Drinking Trajectories in Young Men.","authors":"Hao Chen, Sören Kuitunen-Paul, Maria Garbusow, Marina Lukezic, Quentin J M Huys, Michael A Rapp, Andreas Heinz, Michael N Smolka","doi":"10.1016/j.biopsych.2025.06.028","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.028","url":null,"abstract":"<p><strong>Background: </strong>Expanding our previous findings that model-based/model-free (MB/MF) control-often conceptualized as goal-directed and habitual behavior-at age 18 is associated with alcohol drinking trajectories over three years, this study investigates whether changes in MB/MF control from ages 18 to 21 i) stem from alcohol exposure and ii) predict drinking patterns up to age 24.</p><p><strong>Methods: </strong>We followed a community sample of 124 18-year-old young men for six years. At ages 18 and 21, participants performed a two-step task assessing MB and MF control while undergoing functional magnetic resonance imaging (91 neural datasets). Drinking behavior was assessed using annual interviews complemented by questionnaires every six months. Correlation coefficients assessed the effect of cumulative alcohol exposure from age 18 to 21 on changes in MB/MF parameters. Latent growth curve models evaluated associations between MB/MF changes and drinking trajectories from ages 21 to 24.</p><p><strong>Results: </strong>Alcohol exposure from ages 18 to 21 showed no significant effect on changes of MB/MF control. An increased MB behavioral score was protective for binge drinking, while an increased MF behavioral score predicted higher binge drinking at age 21, but not its future development. Changes in MF ventral striatum signals were associated with escalated consumption score development from ages 21 to 24, whereas MF ventromedial prefrontal signals exhibited a protective effect.</p><p><strong>Conclusions: </strong>Preceding changes in behavioral and neural MB and MF control were linked to future drinking patterns, suggesting that interventions aimed at modulating MB/ MF controls could help mitigate subsequent risky drinking behaviors.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574781","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":"The Interplay Between Sleep and Mental Health: A Genetic Perspective.","authors":"Nataliia Kozhemiako, Carol Mita, Georgia M Panagiotaropoulou, Katie Js Lewis, Tamar Sofer, Shaun M Purcell","doi":"10.1016/j.biopsych.2025.06.024","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.06.024","url":null,"abstract":"<p><p>Although many facets of sleep, including subjective, behavioral and neurophysiological features, are closely linked with psychiatric disorders, the natures of these relationships are generally unclear. A given alteration in sleep could reflect a cause (that may mediate genetic risk), consequence, symptom, trigger, epiphenomenon due to shared determinants, or some combination of these. Genetic approaches can in principle be informative: i) by identifying specific genetic influences on disease mediated by or shared with sleep, which could help the search for biological mechanisms and therapeutic targets; ii) by providing evidence for causality, which could suggest interventions for modifiable sleep traits. Here, we summarize recent human quantitative and molecular genetic studies on sleep and psychiatric disease, including twin and genome-wide association studies. Despite evidence for shared heritability across many domains, notably depression and insomnia, the field is in its early stages and faces significant challenges: i) putative causal effects are small, phenotypically non-specific, not resolved to specific gene pathways and often bidirectional; ii) most current discovery cohorts are demographically biased and do not capture profound age-related changes in sleep and its genetic architecture; iii) group-level analyses ignore patient-to-patient heterogeneity, including the presence or absence of specific sleep alterations; iv) a paucity of objective, brain-based data in genetically-informative samples hampers making connections with sleep neurophysiology. Nonetheless, as ever-growing genetic tools and resources still hold great potential for translational bridges between basic model-systems, human epidemiology and personalized clinical care, genetic approaches will still likely be needed to reveal sleep's roles in maintaining mental health.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574782","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":"Mapping cerebellar connectivity to cognition in psychosis: Convergent evidence from fMRI and TMS.","authors":"Hengyi Cao, Miklos Argyelan, Joanna Yan, Halil Aziz Velioglu, Franky Fang, Andrea Joanlanne, Simran Kang, Lara Prizgint, Jenna Schugart, Kadeem Brown, John Cholewa, Philip Watson, Sunny X Tang, Ricardo Carrion, Jose Rubio, Moein Foroughi, Todd Lencz, Anil K Malhotra","doi":"10.1016/j.biopsych.2025.06.023","DOIUrl":"10.1016/j.biopsych.2025.06.023","url":null,"abstract":"<p><strong>Background: </strong>Cerebellar dysfunction is strongly implicated in both cognition and psychosis, and the \"cognitive dysmetria\" hypothesis posits cognition as the intermediary in the pathway from cerebellar dysfunction to psychopathology. However, the nuanced cerebellum-behavior relationships in psychosis remain unclear. Establishing such link is crucial to understand cerebellar mechanisms and to identify treatment target for cognitive deficits in patients.</p><p><strong>Methods: </strong>We studied 100 patients with early psychosis from the Human Connectome Project Early Psychosis study. Connectome-based predictive modeling was conducted to probe cognitive functions most predicted by cerebellar connectivity. Mediation analysis was performed to test a mediating role of cognition between cerebellar connectivity and symptoms. To further support the causality of the findings, we additionally recruited 16 psychotic patients for a 2-week randomized, sham-controlled cerebellar transcranial magnetic stimulation (TMS) trial.</p><p><strong>Results: </strong>Cerebellar connectivity significantly predicted three cognitive functions, namely, verbal ability, working memory, and cognitive flexibility. Verbal ability fully mediated the relationship between cerebellar connectivity and negative symptoms, in particular alogia. While each cognitive function was predicted by a distinct cerebellar connectivity pattern, the left crus I/II appeared to be a common area with connectivity consistently predicting all three functions. Stimulating this region via TMS showed significantly improved cognitive composite score and medium-to-large effects on scores for memory, verbal, and executive functions.</p><p><strong>Conclusions: </strong>These findings suggest a potential causal pathway from cerebellar connectivity to domain-specific cognitive deficits and psychopathology in schizophrenia. Moreover, they also point to the cerebellum as a potential target for the treatment of cognitive dysfunction in psychotic disorders.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567027","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":"Biological Psychiatry: A Brief Note of Thanks.","authors":"John H Krystal","doi":"10.1016/j.biopsych.2025.06.019","DOIUrl":"10.1016/j.biopsych.2025.06.019","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564328","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":"Blind Mice, African Clawed Frogs, and the Missing Link Between Circadian Rhythms and Psychiatry","authors":"Alexandra Saali ,&nbsp;David A. Ross ,&nbsp;Joseph J. Cooper ,&nbsp;Andrew M. Novick","doi":"10.1016/j.biopsych.2025.05.004","DOIUrl":"10.1016/j.biopsych.2025.05.004","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 2","pages":"Pages 102-104"},"PeriodicalIF":9.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470318","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}