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Biological Psychiatry Pub Date : 2025-03-12 DOI: 10.1016/S0006-3223(25)00083-6

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All Fired Up: Microglial Neuroinflammation in Parkinson’s Disease

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Biological Psychiatry Pub Date : 2025-03-12 DOI: 10.1016/j.biopsych.2025.01.015

Claudia Z. Han

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Biological Psychiatry Pub Date : 2025-03-12 DOI: 10.1016/S0006-3223(25)00080-0

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New Insights Into the Role That Familial Genetic Risk Factors and Severe Infections Play in Increasing the Risk of an Individual to Develop Obsessive-Compulsive Disorder

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Biological Psychiatry Pub Date : 2025-03-12 DOI: 10.1016/j.biopsych.2024.12.016

James F. Leckman

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When, How, and Where: Combining Psychotherapy and Neuromodulation for Obsessive-Compulsive Disorder

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Biological Psychiatry Pub Date : 2025-03-12 DOI: 10.1016/j.biopsych.2025.01.018

Sarah Ann Smith , Katharine Dunlop

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Biological Psychiatry Pub Date : 2025-03-12 DOI: 10.1016/S0006-3223(25)00079-4

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Immune-developmental processes contribute to schizophrenia risk: insights from a genetic overlap study with height.

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Biological Psychiatry Pub Date : 2025-03-10 DOI: 10.1016/j.biopsych.2025.02.902

Cato Romero, Christiaan de Leeuw, Marijn Schipper, Bernardo de A P C Maciel, Martijn P van den Heuvel, Rachel M Brouwer, August B Smit, Frank Koopmans, Danielle Posthuma, Sophie van der Sluis

{"title":"Immune-developmental processes contribute to schizophrenia risk: insights from a genetic overlap study with height.","authors":"Cato Romero, Christiaan de Leeuw, Marijn Schipper, Bernardo de A P C Maciel, Martijn P van den Heuvel, Rachel M Brouwer, August B Smit, Frank Koopmans, Danielle Posthuma, Sophie van der Sluis","doi":"10.1016/j.biopsych.2025.02.902","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.902","url":null,"abstract":"Background: Shorter stature has been phenotypically linked to increased prevalence of schizophrenia (SCZ), but the nature of this association is unknown.Methods: Using genome-wide genetic data, we studied the SCZ-height relationship on a genetic level. Applying novel genetic methods and tools, we analyzed gene-sets, tissue-types, cell-types, local genetic correlation, conditional genetic analyses, and fine-mapping of effector-genes to scrutinize the SCZ-height relationship.Results: We identified 142 genes statistically associated with both SCZ and height and found enrichment in 3 functional gene-sets. Genetic annotations implicated the pituitary and specifically mesenchymal stem cells for height and thyrotropic cells for SCZ. While the global SCZ-height genetic correlation was nonsignificant, 9 genomic regions showed robust local genetic correlations (7 negative, 6 in the MHC-region). The shared genetic signal for SCZ and height within the 6 MHC-regions was partially explained by mutual genetic overlap with white blood cell count, particularly lymphocytes. Fine-mapping prioritized 3 shared effector-genes (GIGYF2, HLA-C, and LIN28B) involved in immune response sensitivity and development of immune and pituitary cell-types.Conclusions: Overall, our findings suggest an involvement during height-development of thyrotropic cells and immune response sensitivity contributing towards risk of SCZ.","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613230","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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Current evidence for the role of rapid-acting antidepressants (RAAD) in bipolar depression? A perspective and plan for action.

IF 9.6 1区医学

Biological Psychiatry Pub Date : 2025-03-08 DOI: 10.1016/j.biopsych.2025.02.903

Jonathan Repple, Maximilian Bayas, Chiara Möser, Nene F Kobayashi, Andreas Reif

{"title":"Current evidence for the role of rapid-acting antidepressants (RAAD) in bipolar depression? A perspective and plan for action.","authors":"Jonathan Repple, Maximilian Bayas, Chiara Möser, Nene F Kobayashi, Andreas Reif","doi":"10.1016/j.biopsych.2025.02.903","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.903","url":null,"abstract":"After decades of limited progress in depression treatment, recent advancements have sparked renewed interest in developing novel antidepressants, particularly rapid-acting antidepressants (RAADs). Despite these promising developments, there remains a significant gap in research on bipolar depression. While several antipsychotics have been investigated for their efficacy in bipolar depression due to the reduced risk of mania induction, research on RAADs, such as (es)ketamine, remains scarce despite their demonstrated safety and effectiveness. This review gives an overview of current developments in RAADs in the context of bipolar disorder. Both published studies as well as phase II, III and IV studies on bipolar depression (based on clinicaltrials.gov) are reviewed in this work. The following RAAD substance classes have been or are currently investigated as possible treatments for bipolar depression: NMDA antagonists and indirect AMPA agonists (ketamine, esketamine, riluzole, felbamate), GABA-A activators or positive allosteric modulators (zuranolone, pregnenolone, PEA), psychedelics (psilocybin, 5-MeO-DMT), muscarine receptor antagonists (scopolamine), and kappa-opioid receptor antagonists (navacaprant). Other than the well-established efficacy and safety of (es)ketamine in treating bipolar depression, there has been little research effort in the treatment of bipolar depression. Recent research into RAADs demonstrates the growing field of novel mechanisms of action in the pharmacological treatment of bipolar depression. However, there is an urgent need for well-controlled clinical studies on RAADs in bipolar depression to expand treatment options and improve outcomes for millions of affected individuals worldwide.","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595990","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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Does the influence of low body-mass index on diagnosis complicate genetic studies of the role of cardiometabolic traits in liability to anorexia nervosa?

IF 9.6 1区医学

Biological Psychiatry Pub Date : 2025-03-07 DOI: 10.1016/j.biopsych.2025.03.002

William R Reay, Kirrilly M Pursey, Jackson G Thorp

{"title":"Does the influence of low body-mass index on diagnosis complicate genetic studies of the role of cardiometabolic traits in liability to anorexia nervosa?","authors":"William R Reay, Kirrilly M Pursey, Jackson G Thorp","doi":"10.1016/j.biopsych.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.03.002","url":null,"abstract":"Anorexia nervosa (AN) is an eating disorder for which the underlying aetiology remains mostly uncharacterised. Large-scale genetic studies of AN suggest a relationship between AN liability and cardiometabolic traits, such as lipid and glycaemic biology, which may reveal novel treatment targets through pharmacological or nutritional interventions. However, the role of body mass index (BMI) in the diagnosis of AN presents a challenge in the interpretation of these genetic studies. Specifically, BMI is a heritable trait with a genetic architecture that is related to cardiometabolic traits. This becomes particularly salient with the emergence of an \"atypical\" AN diagnosis whereby individuals display behaviours consistent with AN, but their BMI remains within normal or higher ranges. In this review, we outline the evidence from genetic studies that support a role of cardiometabolic traits in risk for AN, as well as the unmet need to study cardiometabolic factors in atypical AN. The influence of selection for individuals with low BMI, particularly from large, international studies that rely on cohorts that used older diagnostic criteria, will be discussed, along with efforts from the literature to disentangle these relationships. We conclude that there is at least some evidence that genetic susceptibility to lower BMI may impact the inferred cardiometabolic relationships with AN genetic liability; however, there remains genetic support for a role of metabolic factors in AN risk beyond what is directly attributable to weight related diagnostic considerations alone. Finally, we provide recommendations for future genetic studies exploring cardiometabolic traits across the spectrum of eating disorders.","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584472","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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Effects of Long-Term Cocaine Self-Administration on Kappa Opioid Receptors in Socially Housed Cynomolgus Monkeys as Assessed with PET Imaging and Neuronally Derived Exosomes.

IF 9.6 1区医学

Biological Psychiatry Pub Date : 2025-03-05 DOI: 10.1016/j.biopsych.2025.02.900

Bernard N Johnson, Mia I Allen, Susan H Nader, Kiran Kumar Solingapuram Sai, Ashish Kumar, Yixin Su, Sangeeta Singh, Songye Li, Yiyun Huang, Gagan Deep, Michael A Nader

{"title":"Effects of Long-Term Cocaine Self-Administration on Kappa Opioid Receptors in Socially Housed Cynomolgus Monkeys as Assessed with PET Imaging and Neuronally Derived Exosomes.","authors":"Bernard N Johnson, Mia I Allen, Susan H Nader, Kiran Kumar Solingapuram Sai, Ashish Kumar, Yixin Su, Sangeeta Singh, Songye Li, Yiyun Huang, Gagan Deep, Michael A Nader","doi":"10.1016/j.biopsych.2025.02.900","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.900","url":null,"abstract":"Background: The present study utilized PET imaging to examine how long-term cocaine self-administration (SA) and time-off from cocaine affected kappa opioid receptor (KOR) availability in the brain of previously cocaine-naïve monkeys. In addition, neuronally derived small extracellular vesicles (NDEs) were measured from plasma to identify peripheral measures of KORs.Methods: Female (n=6) and male (n=7) cynomolgus monkeys, living in stable same-sex social groups, were trained to SA intravenous cocaine. PET imaging with the KOR selective agonist [11C]EKAP occurred after monkeys had SA ∼100 mg/kg total cocaine intake and after ∼30 days off from cocaine; in a subset of monkeys, a third PET scan was conducted after ∼100 days off from cocaine. Blood samples were obtained prior to each PET study and NDEs from the plasma were isolated by immunocapture method and analyzed for percentage of KOR+.Results: There were significant interactions between condition (100 mg/kg cocaine, and 30-days off cocaine), sex, and social rank in KOR availability across 7 of 15 brain regions. More specifically, these interactions were associated with increased KOR availability following cocaine SA and after 30-days off from cocaine in dominant females. In a subset of monkeys, no differences were observed in [11C]EKAP binding between 30- and 100-days off from cocaine. NDEs showed significant interactions between sex and condition, providing a peripheral measure consistent with the PET results.Conclusions: These findings extend previous research in socially housed monkeys to the KOR and suggest that KOR may be a viable target for pharmacological interventions for cocaine misuse, especially in women.","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584474","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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