Biological Psychiatry最新文献

{"title":"The genetic architecture of differentiating behavioral and emotional problems in early life.","authors":"Adrian Dahl Askelund, Laura Hegemann, Andrea G Allegrini, Elizabeth C Corfield, Helga Ask, Neil M Davies, Ole A Andreassen, Alexandra Havdahl, Laurie J Hannigan","doi":"10.1016/j.biopsych.2024.12.021","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.12.021","url":null,"abstract":"<p><strong>Background: </strong>Early in life, behavioral and cognitive traits associated with risk for developing a psychiatric condition are broad and undifferentiated. As children develop, these traits differentiate into characteristic clusters of symptoms and behaviors that ultimately form the basis of diagnostic categories. Understanding this differentiation process - in the context of genetic risk for psychiatric conditions, which is highly generalized - can improve early detection and intervention.</p><p><strong>Methods: </strong>We modeled the differentiation of behavioral and emotional problems from age 1.5-5 years (behavioral problems - emotional problems = differentiation score) in a pre-registered study of ∼79,000 children from the population-based Norwegian Mother, Father, and Child Cohort Study. We used genomic structural equation modeling to identify genetic signal in differentiation and total problems, investigating their links with 11 psychiatric and neurodevelopmental conditions. We examined associations of polygenic scores (PGS) with both outcomes and assessed the relative contributions of direct and indirect genetic effects in ∼33,000 family trios.</p><p><strong>Results: </strong>Differentiation was primarily genetically correlated with psychiatric conditions via a \"neurodevelopmental\" factor. Total problems were primarily associated with the \"neurodevelopmental\" factor and \"p\"-factor. PGS analyses revealed an association between liability to ADHD and differentiation (β=0.11 [0.10,0.12]), and a weaker association with total problems (β=0.06 [0.04,0.07]). Trio-PGS analyses showed predominantly direct genetic effects on both outcomes.</p><p><strong>Conclusions: </strong>We uncovered genomic signal in the differentiation process, mostly related to common variants associated with neurodevelopmental conditions. Investigating the differentiation of early life behavioral and emotional problems may enhance our understanding of the developmental emergence of different psychiatric and neurodevelopmental conditions.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963666","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":"One BAG doesn't fit all: the differences and similarities of BAG family members in mediating CNS homeostasis.","authors":"Heng Lin, Sudarshan Ramanan, Sofia Kaplan, Darron H King, Dominic Bunn, Gail Vw Johnson","doi":"10.1016/j.biopsych.2024.12.019","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.12.019","url":null,"abstract":"<p><p>There is an increasing awareness that B-cell lymphoma 2 (Bcl-2)-associated athanogene (BAG) proteins play critical roles in maintaining neural homeostasis, and that their dysregulation contributes to neurological disorders. This protein family of nine members is evolutionarily conserved, with each member having at least one BAG domain that binds to the nucleotide-binding domains of Heat Shock Protein (Hsp) 70 family members. Collectively, these proteins are essential for the proper functioning of the central nervous system (CNS). Although there are numerous studies that focus on a specific BAG protein, an understanding of how BAG family members may act cooperatively to maintain cellular homeostasis is needed. In this review, we give an overview of the BAG domain interactors, Hsp72, Hsp70.2, CHIP and METTL3 which are common to all BAG family members. This is followed by a concise description of each BAG family member, with a focus on its function in the CNS and dysfunction in neurological conditions. Finally, we discuss the intersection of the molecular functions of the different BAG family proteins by delineating differences and similarities, and describing how their functions can be either complementary or competing. The information in this review provides a basic conceptual framework for analyzing the roles of a particular BAG family member in the CNS and neurological conditions. This review also provides a basis for examining how BAG family members can play either redundant or antagonistic roles that may modulate experimental outcomes.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963661","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 Dark Side of Empathy: the Role of Excessive Affective Empathy on Mental Health Disorders.","authors":"Chaoli Huang, Zifeng Wu, Sha Sha, Cunming Liu, Ling Yang, Peng Jiang, Hongxing Zhang, Chun Yang","doi":"10.1016/j.biopsych.2024.12.020","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.12.020","url":null,"abstract":"<p><p>Empathy, typically regarded as a positive attribute, is now being critically evaluated for its potential negative implications on mental health. A growing body of research indicates that excessive empathy, particularly high level of affective empathy, can lead to overwhelming emotional states, increasing susceptibility to psychological distress and psychiatric disorders. This review aims to explore the negative effects of empathy on mental health. We review both human and animal studies concerning the relationship between empathy and psychological disorders, revealing that while empathy enhances social interactions and emotional understanding, it may also heighten empathic distress and potentially contribute to the development of pain, internalizing disorders, depression, anxiety, emotional over-involvement, burnout, vicarious trauma and post-traumatic stress disorder. This review contributes to the broader discourse on empathy by delineating its dual impacts, integrating insights from neurobiology, psychology, and behavioral studies. This review may enhance our understanding of empathy's complex role in mental health, offering a nuanced perspective that acknowledges both its beneficial and detrimental impacts.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963663","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":"Early Risk Identification and Prevention of Bipolar Disorder: Ethical Considerations and User Perspectives.","authors":"Rudolf Uher, Alyson Zwicker","doi":"10.1016/j.biopsych.2024.12.017","DOIUrl":"10.1016/j.biopsych.2024.12.017","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926373","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":"Machine Learning Analysis of the Orbitofrontal Cortex Transcriptome of Human Opioid Users Identifies Shisa7 as a Translational Target Relevant for Heroin Seeking Leveraging a Male Rat Model.","authors":"Randall J Ellis, Jacqueline-Marie N Ferland, Tanni Rahman, Joseph L Landry, James E Callens, Gaurav Pandey, TuKiet Lam, Jean Kanyo, Angus C Nairn, Stella Dracheva, Yasmin L Hurd","doi":"10.1016/j.biopsych.2024.12.007","DOIUrl":"10.1016/j.biopsych.2024.12.007","url":null,"abstract":"<p><strong>Background: </strong>Identifying neurobiological targets predictive of the molecular neuropathophysiological signature of human opioid use disorder (OUD) could expedite new treatments. OUD is characterized by dysregulated cognition and goal-directed behavior mediated by the orbitofrontal cortex (OFC), and next-generation sequencing could provide insights regarding novel targets.</p><p><strong>Methods: </strong>Here, we used machine learning to evaluate human postmortem OFC RNA sequencing datasets from heroin users and control participants to identify transcripts that were predictive of heroin use. To determine a causal link to OUD-related behaviors, we examined the effects of overexpressing the top target gene in a translational rat model of heroin seeking and behavioral updating. Additionally, we determined the effects of overexpression on the rat OFC transcriptome compared with that of human heroin users. Co-immunoprecipitation/mass spectrometry (co-IP/MS) from the rat OFC elucidated the protein complex of the novel target.</p><p><strong>Results: </strong>Our machine learning approach identified SHISA7 as predictive of human heroin users. Shisa7 is understudied but appears to be an auxiliary protein of GABA_A (gamma-aminobutyric acid A) or AMPA receptors. In rats, Shisa7 expression positively correlated with heroin-seeking behavior. Overexpressing Shisa7 in the OFC augmented heroin seeking and impaired behavioral updating for sucrose-based operant contingency. RNA sequencing of rat OFC revealed gene coexpression networks regulated by Shisa7 overexpression similar to human heroin users. Finally, co-IP/MS showed that heroin influenced Shisa7 binding to glutamatergic and GABAergic receptor subunits. Both gene expression signatures and Shisa7 protein complex emphasized perturbations of neurodegenerative and neuroimmune processes.</p><p><strong>Conclusions: </strong>Our findings suggest that OFC Shisa7 is a critical driver of neurobehavioral pathology related to drug-seeking behavior and behavioral updating, thus identifying a potential therapeutic target for OUD.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891635","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":"Responsible use of population neuroscience data: Towards standards of accountability and integrity.","authors":"Sandra A Brown, Hugh Garavan, Terry L Jernigan, Susan F Tapert, Rebekah S Huber, Daniel Lopez, Traci Murray, Gayathri Dowling, Elizabeth A Hoffman, Lucina Q Uddin","doi":"10.1016/j.biopsych.2024.12.014","DOIUrl":"10.1016/j.biopsych.2024.12.014","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891755","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":"A Multiform Heterogeneity Framework for Alzheimer's Disease Based on Multimodal Neuroimaging.","authors":"Kun Zhao, Pindong Chen, Dong Wang, Rongshen Zhou, Guolin Ma, Yong Liu","doi":"10.1016/j.biopsych.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.12.009","url":null,"abstract":"<p><p>Understanding the heterogeneity of Alzheimer's disease (AD) is crucial for advancing precision medicine specifically tailored to this disorder. Recent research has deepened our understanding of AD heterogeneity, yet translating these insights from bench to bedside via neuroimaging heterogeneity frameworks presents significant challenges. In this review, we systematically revisit prior studies and summarize the existing methodology of data-driven neuroimaging studies for AD heterogeneity. We organized the present methodology into (i) a subtyping cluster strategy for AD patients, and we also subdivided it into subtyping analysis based on cross-sectional multimodal neuroimaging profiles, and the identification of long-term disease progression from short-term datasets; (ii) a stratified strategy that integrates neuroimaging measures with biomarkers; (iii) individual-specific abnormal patterns based on the Normative model. We then evaluated the characteristics of these studies along two dimensions: (i) the understanding of pathology and (ii) clinical application. We systematically address the limitations, challenges, and future directions of research into AD heterogeneity. Our goal is to enhance the neuroimaging heterogeneity framework for AD, facilitating its transition from bench to bedside.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891632","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":"Old strategies, new environments: Reinforcement Learning on social media.","authors":"Georgia Turner, Amanda M Ferguson, Tanay Katiyar, Stefano Palminteri, Amy Orben","doi":"10.1016/j.biopsych.2024.12.012","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.12.012","url":null,"abstract":"<p><p>The rise of social media has profoundly altered the social world - introducing new behaviours which can satisfy our social needs. However, it is yet unknown whether human social strategies, which are well-adapted to the offline world we developed in, operate as effectively within this new social environment. Here, we describe how the computational framework of Reinforcement Learning can help us to precisely frame this problem and diagnose where behaviour-environment mismatches emerge. The Reinforcement Learning framework describes a process by which an agent can learn to maximise their long-term reward. Reinforcement Learning, which has proven successful in characterising human social behaviour, consists of three stages: updating expected reward, valuating expected reward by integrating subjective costs such as effort, and selecting an action. Specific social media affordances, such as the quantifiability of social feedback, might interact with the Reinforcement Learning process at each of these stages. In some cases, affordances can exploit Reinforcement Learning biases which are beneficial offline, by violating the environmental conditions under which such biases are optimal - such as when algorithmic personalisation of content interacts with confirmation bias. Characterising the impact of specific aspects of social media through this lens can improve our understanding of how digital environments shape human behaviour. Ultimately, this formal framework could help address pressing open questions about social media use, including its changing role across human development, and its impact on outcomes such as mental health.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891750","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":"Negative valence in Obsessive-Compulsive Disorder: A worldwide mega-analysis of task-based functional neuroimaging data of the ENIGMA-OCD consortium.","authors":"Nadza Dzinalija, Chris Vriend, Lea Waller, H Blair Simpson, Iliyan Ivanov, Sri Mahavir Agarwal, Pino Alonso, Lea L Backhausen, Srinivas Balachander, Aniek Broekhuizen, Miguel Castelo-Branco, Ana Daniela Costa, Hailun Cui, Damiaan Denys, Isabel Catarina Duarte, Goi Khia Eng, Susanne Erk, Sophie M D D Fitzsimmons, Jonathan Ipser, Fern Jaspers-Fayer, Niels T de Joode, Minah Kim, Kathrin Koch, Jun Soo Kwon, Wieke van Leeuwen, Christine Lochner, Hein J F van Marle, Ignacio Martinez-Zalacain, Jose M Menchon, Pedro Morgado, Janardhanan C Narayanaswamy, Ian S Olivier, Maria Picó-Pérez, Tjardo S Postma, Daniela Rodriguez-Manrique, Veit Roessner, Oana Georgiana Rus-Oswald, Venkataram Shivakumar, Carles Soriano-Mas, Emily R Stern, S Evelyn Stewart, Anouk L van der Straten, Bomin Sun, Sophia I Thomopoulos, Dick J Veltman, Nora C Vetter, Henny Visser, Valerie Voon, Henrik Walter, Ysbrand D van der Werf, Guido van Wingen, Dan J Stein, Paul M Thompson, Ilya M Veer, Odile A van den Heuvel","doi":"10.1016/j.biopsych.2024.12.011","DOIUrl":"10.1016/j.biopsych.2024.12.011","url":null,"abstract":"<p><strong>Objective: </strong>Obsessive-compulsive disorder (OCD) is associated with altered brain function related to processing of negative emotions. To investigate neural correlates of negative valence in OCD, we pooled fMRI data of 633 individuals with OCD and 453 healthy controls from 16 studies using different negatively-valenced tasks across the ENIGMA-OCD Working-Group.</p><p><strong>Methods: </strong>Participant data were processed uniformly using HALFpipe, to extract voxelwise participant-level statistical images of one common first-level contrast: negative vs. neutral stimuli. In pre-registered analyses, parameter estimates were entered into Bayesian multilevel models to examine whole-brain and regional effects of OCD and its clinically relevant features - symptom severity, age of onset, and medication status.</p><p><strong>Results: </strong>We provided a proof-of-concept that participant-level data can be combined across several task paradigms and observed one common task activation pattern across individuals with OCD and controls that encompasses fronto-limbic and visual areas implicated in negative valence. Compared to controls, individuals with OCD showed very strong evidence of weaker activation of the bilateral occipital cortex (P+<0.001) and adjacent visual processing regions during negative valence processing that was related to greater OCD severity, late-onset of disease and an unmedicated status. Individuals with OCD also showed stronger activation in the orbitofrontal, subgenual anterior cingulate and ventromedial prefrontal cortex (all P+<0.1) that was related to greater OCD severity and late onset.</p><p><strong>Conclusion: </strong>In the first mega-analysis of this kind, we replicate previous findings of stronger ventral prefrontal activation in OCD during negative valence processing and highlight the lateral occipital cortex as an important region implicated in altered negative valence processing.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891557","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":"Psychotropic Taxonomies: Constructing a Therapeutic Framework for Psychiatry.","authors":"Robert A McCutcheon, Philip Cowen, Matthew M Nour, Toby Pillinger","doi":"10.1016/j.biopsych.2024.12.004","DOIUrl":"10.1016/j.biopsych.2024.12.004","url":null,"abstract":"<p><p>Pharmacological interventions are a cornerstone of psychiatric practice. The taxonomies used to classify these interventions influence the treatment and interpretation of psychiatric symptoms. Disease-based classification systems (e.g., antidepressant and antipsychotic) do not reflect the fact that psychotropic agents are used across diagnostic categories or account for the dimensional nature of both the psychopathology and biology of psychiatric illnesses. In this review, we discuss the history of psychotropic drug taxonomies and their influence on both clinical practice and drug development. We frame taxonomies as existing on a spectrum, with high-level disease-based approaches at one end and target-based molecular approaches at the other. Finally, we consider how data-driven methods might address the issue of classification at an intermediate level, based around transdiagnostic neurobiological and psychopathological markers.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871235","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}