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Biological Psychiatry Pub Date : 2025-09-17 DOI: 10.1016/S0006-3223(25)01414-3

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Biological Psychiatry Pub Date : 2025-09-17 DOI: 10.1016/S0006-3223(25)01417-9

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Intrinsic Deacetylation Represses Intrinsic Excitation: HDAC5 and Cocaine Substance Use Disorder 内在去乙酰化抑制内在兴奋：HDAC5和可卡因物质使用障碍。

IF 9 1区医学

Biological Psychiatry Pub Date : 2025-09-17 DOI: 10.1016/j.biopsych.2025.08.002

Elizabeth A. Heller

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IF 9 1区医学

Biological Psychiatry Pub Date : 2025-09-17 DOI: 10.1016/S0006-3223(25)01413-1

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Dynamic Cytokine Relationships Across the Blood-Brain Barrier in Humans and Non-Human Primates, Implications for Psychiatric Illness: A Systematic Review. 人类和非人类灵长类动物血脑屏障中细胞因子的动态关系，对精神疾病的影响：系统综述。

IF 9 1区医学

Biological Psychiatry Pub Date : 2025-09-12 DOI: 10.1016/j.biopsych.2025.08.022

Rahul Tyagi, Christopher M Bartley

{"title":"Dynamic Cytokine Relationships Across the Blood-Brain Barrier in Humans and Non-Human Primates, Implications for Psychiatric Illness: A Systematic Review.","authors":"Rahul Tyagi, Christopher M Bartley","doi":"10.1016/j.biopsych.2025.08.022","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.08.022","url":null,"abstract":"Cytokines are immune signaling molecules that also function as neuromodulators. Cytokines are elevated in the peripheral blood of some individuals with mental disorders, suggesting that inflammation may contribute to their illness. Furthermore, immune therapy trials for systemic inflammatory disorders have reported improvements in anxiety and depression as secondary endpoints. These findings bolster the salutary potential for anti-inflammatory treatment of primary psychiatric populations. However, immunotherapeutic trials in depression and other psychiatric disorders have largely yielded inconclusive or negative results. One possibility is the reliance of clinical trial designs on cross-sectional measurements of inflammatory markers in blood. Peripheral cytokine profiles may not reflect central inflammatory states and cannot disclose dynamic relationships between compartments. Because central cytokines directly modulate neural activity, mapping their dynamic relationships between the periphery and central nervous system may improve future clinical trial designs. Therefore, we performed a systematic search for studies that measured cytokines at multiple time points in paired blood and cerebrospinal fluid samples from humans and non-human primates. Our narrative synthesis of these studies found that peripheral and central cytokine fluctuations are uncorrelated in humans under basal conditions. Moreover, an evoked increase in a cytokine's level peripherally may provoke a dramatic increase in a distinct cytokine centrally without eliciting a meaningful change in its own central level (cross-correlation in the absence of autocorrelation). Furthermore, physical and psychological stressors can induce compartment-specific cytokine changes and correlations. These initial observations highlight the need for a more complete map of cytokine dynamics in humans with and without mental illness.","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063489","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}

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Overview of Challenges in Brain-based Predictive Modeling: Towards meaningful predictive insights. 基于大脑的预测建模挑战概述：迈向有意义的预测见解。

IF 9 1区医学

Biological Psychiatry Pub Date : 2025-09-12 DOI: 10.1016/j.biopsych.2025.09.003

Vera Komeyer, Nicolas Nieto, Simon B Eickhoff, Federico Raimondo, Kaustubh R Patil

{"title":"Overview of Challenges in Brain-based Predictive Modeling: Towards meaningful predictive insights.","authors":"Vera Komeyer, Nicolas Nieto, Simon B Eickhoff, Federico Raimondo, Kaustubh R Patil","doi":"10.1016/j.biopsych.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.09.003","url":null,"abstract":"Predictive analytics based on machine learning (ML) and artificial intelligence is a powerful tool enabling precision psychiatry and providing insights into brain-behavior relationships. However, given the mixed results observed in the field so far, making meaningful progress requires careful consideration of several key challenges to ensure the validity of models and findings, including overfitting, confounding biases, site effect harmonization, and interpretability, among others. First, we highlight limitations of cross-validation (CV), a ubiquitous ML strategy used to prevent overfitting and obtain generalization estimates, emphasizing the risk of performance inflation and the need for independent validation. Next, we introduce different types of so-called 3rd variables that can influence the examination of a brain-behavioral relationship of interest in different ways, using causal inference principles. We emphasize the biasing impact of confounding variables on ML models and summarize common mitigation strategies. We then discuss site-specific effects in multi-site datasets, reviewing different harmonization strategies to reduce unwanted variability and site-specific noise. Finally, we explore post-hoc model interpretation methods to enhance model transparency while cautioning against misinterpretation. By integrating rigorous result validation, confounder control, and interpretability techniques, researchers can ensure that ML models produce more reliable and generalizable findings avoiding spurious associations.","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063517","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}

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Distinct Amygdala Neuronal Populations Control Opioid Use and Withdrawal in Mice. 不同的杏仁核神经元群控制小鼠阿片类药物的使用和戒断。

IF 9 1区医学

Biological Psychiatry Pub Date : 2025-09-09 DOI: 10.1016/j.biopsych.2025.08.021

Lucas Silva Tortorelli, Henry Zin Oo, Suyun Hahn, Yocasta Alvarez-Bagnarol, Yarimar Carrasquillo, Leandro F Vendruscolo

{"title":"Distinct Amygdala Neuronal Populations Control Opioid Use and Withdrawal in Mice.","authors":"Lucas Silva Tortorelli, Henry Zin Oo, Suyun Hahn, Yocasta Alvarez-Bagnarol, Yarimar Carrasquillo, Leandro F Vendruscolo","doi":"10.1016/j.biopsych.2025.08.021","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.08.021","url":null,"abstract":"Background: Opioid use disorder (OUD) is a chronic and recurring psychiatric disorder that is associated with high morbidity and mortality. The central nucleus of the amygdala (CeA) undergoes neuroadaptations in both humans with OUD and opioid-dependent rodents. As part of a heterogeneous microcircuits, the CeA integrates internal and external sensory inputs that drive innate and adaptive behaviors. Key CeA neuronal populations, including protein kinase C-δ (PKC-δ), corticotropin-releasing factor (CRF), and somatostatin (SST) neurons, regulate behaviors that are disrupted in addiction, such as pain, stress, reward function, and anxiety/arousal. We hypothesized that these CeA neuronal populations differentially regulate opioid-related behaviors.Methods: We used in situ hybridization to characterize the expression of μ-opioid receptor (MOR; Oprm1), and to assess the functional role of these CeA neuronal populations, we used behavioral and molecular approaches in opioid-dependent mice.Results: We identified a decrease Oprm1 mRNA expression in the CeA in opioid-dependent mice that were undergoing withdrawal compared with nondependent mice. In contrast, the expression of PKC-δ (Prkcd), CRF (Crh), and SST (Sst) mRNA levels remained unchanged. The chemogenetic inhibition of CeAPKC-δ neurons decreased fentanyl vapor self-administration and alleviated fentanyl withdrawal-induced hyperalgesia. The inhibition of CeACRF neurons reduced irritability and somatic withdrawal signs. The activation of CeASST neurons reduced somatic withdrawal signs.Conclusions: These findings suggest that distinct CeA neuronal populations uniquely regulate different aspects of opioid use and withdrawal, highlighting cell-type specific targets for potential therapeutic interventions.","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038928","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}

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Neural tracking of social navigation in autism spectrum disorder. 自闭症谱系障碍社会导航的神经跟踪。

IF 9 1区医学

Biological Psychiatry Pub Date : 2025-09-08 DOI: 10.1016/j.biopsych.2025.08.018

Sarah M Banker, Matthew Schafer, Sarah Barkley, Jadyn Trayvick, Alissa Chen, Arabella W Peters, Abigaël A Thinakaran, Xiaosi Gu, Jennifer H Foss-Feig, Daniela Schiller

{"title":"Neural tracking of social navigation in autism spectrum disorder.","authors":"Sarah M Banker, Matthew Schafer, Sarah Barkley, Jadyn Trayvick, Alissa Chen, Arabella W Peters, Abigaël A Thinakaran, Xiaosi Gu, Jennifer H Foss-Feig, Daniela Schiller","doi":"10.1016/j.biopsych.2025.08.018","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.08.018","url":null,"abstract":"Background: As we navigate changing social landscapes, maintaining maps of interpersonal dynamics can help guide our choices. Autism spectrum disorder (ASD) is associated with social challenges that may affect the accumulation or application of social information. However, little is known about social cognitive mapping in autistic adults.Methods: Herein, we investigate differences in social navigation amongst 122 adults with ASD, typical development (TD), and misophonia (included as a clinical comparison group) using a social interaction task during fMRI.Results: Compared to other groups, adults with ASD behaved socially distant from task characters. Nevertheless, the groups displayed comparable neural tracking of social distances in regions previously identified in non-clinical samples (1-3), including the posterior cingulate cortex (PCC), as well as the parahippocampal place area (PPA), where tracking uniquely related to cross-diagnostic social avoidance symptoms. In contrast, the ASD group displayed distinctive hypoactivity in the temporal pole (TP) during social decisions, associated with smaller real-world social networks and reduced insight into their external symptoms. Additionally, while the TD and misophonia groups displayed functional decoupling between the TP and PCC during social decisions, this was not detected in ASD.Conclusions: Adults with ASD displayed distinct behaviors and neural activity during deliberation in social interactions. Yet, brain systems supporting social mapping appear preserved across groups, consistent with prior findings, now extended to a clinically diverse sample. These results highlight both shared and ASD-specific neural mechanisms of social navigation, offering insight into potential neural differences in how social evidence guides choices in ASD.","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032687","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}

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RNA in plasma extracellular vesicles of adolescent rhesus macaques reveal immune, bioenergetic and microbial imprints of early life adversity - an exploratory analysis. 青春期恒河猴血浆细胞外囊泡中的RNA揭示了早期生活逆境的免疫，生物能量和微生物印记-一项探索性分析。

IF 9 1区医学

Biological Psychiatry Pub Date : 2025-09-08 DOI: 10.1016/j.biopsych.2025.08.020

Laura Korobkova, Matthew E Thornton, Matthew A Collin, Elyse L Morin, Hadj Aoued, Soma Sannigrahi, Nabeel Bhinderwala, Kristie M Garza, Erin R Siebert, Hasse Walum, Ryan P Cabeen, Brendan H Grubbs, Mar M Sanchez, Brian G Dias

{"title":"RNA in plasma extracellular vesicles of adolescent rhesus macaques reveal immune, bioenergetic and microbial imprints of early life adversity - an exploratory analysis.","authors":"Laura Korobkova, Matthew E Thornton, Matthew A Collin, Elyse L Morin, Hadj Aoued, Soma Sannigrahi, Nabeel Bhinderwala, Kristie M Garza, Erin R Siebert, Hasse Walum, Ryan P Cabeen, Brendan H Grubbs, Mar M Sanchez, Brian G Dias","doi":"10.1016/j.biopsych.2025.08.020","DOIUrl":"10.1016/j.biopsych.2025.08.020","url":null,"abstract":"Background: Exposure to early life adversity (ELA), including childhood maltreatment, is one of the most significant risk factors for the emergence of psychosomatic disorders in adolescence and adulthood. Most investigations into biological processes that have been perturbed by ELA have profiled DNA methylation in whole blood and coalesced around perturbations of immunobiology being centrally insulted by ELA.Methods: To identify novel molecular signatures that are enduringly perturbed by childhood maltreatment, we isolated circulating extracellular vesicles (EVs) from plasma collected from adolescent rhesus macaques that had either experienced nurturing maternal care (CONT, n = 7, 4M 3F) or maltreatment in infancy (MALT, n = 6, 3M 3F). Next, we profiled the RNA found in these EVs.Results: RNA associated with genes related to translation, ATP synthesis, mitochondrial function and immune response were downregulated in circulating EVs collected from adolescent macaques that had experienced maltreatment during infancy, while those involved in ion transport, metabolism and cell differentiation were upregulated in these EVs. Additionally, a significant proportion of EV RNA aligned to the microbiome and maltreatment during infancy altered the diversity of microbiome-associated RNA signatures found in EVs.Conclusions: Our findings provide evidence that alterations in RNA associated with immune function, cellular energetics and the microbiome in circulating EVs may serve as enduring biomarkers of prior exposure to ELA. As a corollary, perturbations of these RNA profiles may offer novel molecular insight into how biology can remain altered long after the shadow of ELA has passed.","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032721","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}

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Developing Clinically Interpretable Neuroimaging Biotypes in Psychiatry. 在精神病学中发展临床可解释的神经影像学生物型。

IF 9 1区医学

Biological Psychiatry Pub Date : 2025-09-08 DOI: 10.1016/j.biopsych.2025.08.019

Jeesung Ahn, Lara Foland-Ross, Teddy J Akiki, Leyla Boyar, Isabelle Wydler, Catherine Bostian, Xue Zhang, Hyun-Joon Yang, Andrea Ellsay, Erica Ma, Divya Rajasekharan, Paul Holtzheimer, Kelvin Lim, Michelle Madore, Noah Philip, Olu Ajilore, Jun Ma, Leanne M Williams

{"title":"Developing Clinically Interpretable Neuroimaging Biotypes in Psychiatry.","authors":"Jeesung Ahn, Lara Foland-Ross, Teddy J Akiki, Leyla Boyar, Isabelle Wydler, Catherine Bostian, Xue Zhang, Hyun-Joon Yang, Andrea Ellsay, Erica Ma, Divya Rajasekharan, Paul Holtzheimer, Kelvin Lim, Michelle Madore, Noah Philip, Olu Ajilore, Jun Ma, Leanne M Williams","doi":"10.1016/j.biopsych.2025.08.019","DOIUrl":"10.1016/j.biopsych.2025.08.019","url":null,"abstract":"Despite available treatments, major depressive disorder (MDD) remains one of the leading causes of disability across medical conditions. The current symptom-based diagnostic system groups patients with highly heterogeneous presentations, with no biomarkers to guide treatment-akin to diagnosing heart disease solely by chest pain, without imaging to reveal the underlying pathology. Lacking biological guidance, clinicians rely on trial-and-error prescribing. Only 33% of individuals with MDD achieve remission on initial treatments, and most cycle through multiple treatments over an average of seven years. The risk of relapse increases with each treatment failure, rising from 50% to 90%. This critical review synthesizes studies showing how functional MRI (fMRI) can predict treatment outcomes and identify which treatment is most effective for an individual based on their brain circuit profile. We illustrate one such method: a theoretically informed approach that quantifies dysfunction across six large-scale brain circuits, relative to healthy reference norms. The resulting personalized circuit scores serve as predictors of response or failure and as moderators of differential treatment outcomes. Matching treatment to a patient's biotype, defined by their circuit profile, has the potential to double remission rates compared to unmatched treatment. We place this example in the broader context of precision imaging approaches to parsing MDD heterogeneity. We also discuss key challenges, limitations, and future directions for translating fMRI-based tools into clinical practice.","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032640","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}

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