Marina Guizzetti, Regina A Mangieri, Lubov A Ezerskiy, Joel G Hashimoto, Michal Bajo, Sean P Farris, Gregg E Homanics, Amy W Lasek, R Dayne Mayfield, Robert O Messing, Marisa Roberto
{"title":"Astrocytes and Alcohol Throughout the Lifespan.","authors":"Marina Guizzetti, Regina A Mangieri, Lubov A Ezerskiy, Joel G Hashimoto, Michal Bajo, Sean P Farris, Gregg E Homanics, Amy W Lasek, R Dayne Mayfield, Robert O Messing, Marisa Roberto","doi":"10.1016/j.biopsych.2025.04.013","DOIUrl":"10.1016/j.biopsych.2025.04.013","url":null,"abstract":"<p><p>Evidence for involvement of astrocytes in several neurodegenerative disorders and in drug addiction has been emerging over the last 2 decades, but only in recent years have astrocytes been investigated for their roles in alcohol use disorder (AUD). As a result, there is a need to evaluate the existing preclinical literature that supports the involvement of astrocytes in the effects of alcohol exposure. Here, we review emerging evidence about responses of astrocytes to alcohol and the contributions of astrocytes to the development of AUD. We review studies of single-cell RNA sequencing with a focus on alcohol and astrocyte heterogeneity, astrocyte reactivity, and the role of astrocytes in remodeling the extracellular matrix. Effects of alcohol on astrocyte-modulated synaptic transmission are also discussed, with an emphasis on studies that have never been reviewed before. Because astrocytes play essential roles in brain development, we review recent research on the role of astrocytes in fetal alcohol spectrum disorder (FASD), which may also shed light on fetal development of psychiatric disorders that have a high prevalence in individuals affected by FASD. Finally, this review highlights gaps in knowledge about astrocyte biology and alcohol that need further research. Particularly, there is a dire need to identify astrocyte subpopulations and molecules that are susceptible to alcohol exposure and may be targets for therapeutic intervention.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965637","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":"From Physiology to Psychiatry: Key role of vagal interoceptive pathways in emotional control.","authors":"Jean-Philippe Krieger, Karolina P Skibicka","doi":"10.1016/j.biopsych.2025.04.012","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.04.012","url":null,"abstract":"<p><p>Interoception is the awareness of bodily sensations, conveyed by both hormonal and neural signals. The vagus nerve is the primary neural interoceptive conduit, responsible for transmitting information from peripheral organs to the brain. It is widely accepted that vagal signals are essential for purely physiological functions like blood pressure maintenance, or nutrient intake homeostasis. However, a growing body of evidence, taking advantage of new technological advances, suggests that the vagus nerve also orchestrates or tunes emotions. Disruption of vagal interoceptive feedback prevents normal emotional control in rodents. Importantly, accumulating evidence indicates that pathological disruption of vagal afferent signals also occurs in humans and may constitute an important risk factor for emotional disorders. Hence, alleviating vagal interoceptive deficits may constitute a new therapeutic avenue for neurotic and affective disorders. Considering the technical and safety challenges for direct stimulation of brain regions relevant to emotionality disorders, the vagus nerve offers a safer and more practical route of potentially achieving similar outcomes. Here we will highlight the earliest studies which examined the consequences of manipulations of the vagal afferent neurons on anxiety, fear, and mood, and integrate these older findings with new research investigating the necessity of vagal afferent neurons in mediating the anxiety or mood-altering effects of physiological signals. We will also discuss the evolutionary significance of vagal control over emotional states within the boundaries of \"normal\" physiology and conclude by discussing the challenges of engaging the vagal interoception as novel therapeutics in mental health disorders.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976976","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}
Aina Badia-Soteras, Aline Mak, Thomas M Blok, Cristina Boers-Escuder, Michel C van den Oever, Rogier Min, August B Smit, Mark H G Verheijen
{"title":"Astrocyte-Synapse Structural Plasticity in Neurodegenerative and Neuropsychiatric Diseases.","authors":"Aina Badia-Soteras, Aline Mak, Thomas M Blok, Cristina Boers-Escuder, Michel C van den Oever, Rogier Min, August B Smit, Mark H G Verheijen","doi":"10.1016/j.biopsych.2025.04.011","DOIUrl":"10.1016/j.biopsych.2025.04.011","url":null,"abstract":"<p><p>Synaptic dysfunction is a common feature across a broad spectrum of brain diseases, spanning from psychopathologies such as posttraumatic stress disorder and substance use disorders to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. While neuroscience research aiming to understand the mechanisms underlying synaptic dysfunction has traditionally focused on the neuronal elements of the synapse, recent research increasingly acknowledges the contribution of astrocytes as a third element controlling synaptic transmission. This also sparked interest to investigate the tripartite synapse and its role in the etiology of neurological diseases. According to recent evidence, changes in the structural interaction between astrocytes and synapses not only play a pivotal role in modulating synaptic function and behavioral states, but also are implicated in the initiation and progression of various brain diseases. This review aims to integrate recent findings that provide insight into the molecular mechanisms underpinning astrocytic structural changes at the synapse. We present a comprehensive discussion of the potential implications of compromised astrocyte-synapse interactions and suggest that astrocytic synaptic coverage is generally reduced in numerous neurological disorders, with the extent of it being disease and stage specific. Finally, we propose outstanding questions on astrocyte-synapse structural plasticity that are relevant for future therapeutic strategies to address neurodegenerative and neuropsychiatric diseases.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973291","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}
Thomas Contesse, Joana Gomes-Ribeiro, Lea Royon, Hugo Fofo, Anaelle Braine, Christelle Glangetas, Shiliang Zhang, M Flavia Barbano, Mariano Soiza-Reilly, François Georges, Jacques Barik, Sebastian P Fernandez
{"title":"Social Stress Increases Anxiety by GluA1-Dependent Synaptic Strengthening of Ventral Tegmental Area Inputs to the Basolateral Amygdala.","authors":"Thomas Contesse, Joana Gomes-Ribeiro, Lea Royon, Hugo Fofo, Anaelle Braine, Christelle Glangetas, Shiliang Zhang, M Flavia Barbano, Mariano Soiza-Reilly, François Georges, Jacques Barik, Sebastian P Fernandez","doi":"10.1016/j.biopsych.2025.04.007","DOIUrl":"10.1016/j.biopsych.2025.04.007","url":null,"abstract":"<p><strong>Background: </strong>Brain defensive mechanisms evolved to maintain low levels of state anxiety. However, risk factors such as stress exposure shift activity within defensive circuits, resulting in increased anxiety. The amygdala is a crucial node for maintaining adaptive anxiety levels, and amygdala hyperactivity can lead to pathological anxiety through mechanisms that are not well understood.</p><p><strong>Methods: </strong>We used chronic social defeat stress (CSDS) in mice. We combined anatomical tracing methods, patch-clamp recordings, and optogenetics to probe how synaptic inputs from the ventral tegmental area (VTA) to the basolateral amygdala (BLA) are affected by CSDS. We performed in vivo fiber photometry recordings to track inputs onto the BLA. Array tomography and electron microscopy were used to unravel the structural composition of VTA-BLA synapses.</p><p><strong>Results: </strong>We identified the VTA as a source of glutamatergic inputs to the BLA potentiated by stress. Inputs from the medial prefrontal cortex were not potentiated. BLA-projecting VTA glutamatergic neurons were activated by social stress, which increased their excitability and synaptic strength. In vivo potentiation of VTA glutamatergic inputs in the BLA was sufficient to increase anxiety. We showed that stress-induced synaptic strengthening was mediated by insertion of GluA1-containing AMPA receptors. Impeding GluA1 subunit trafficking in BLA neurons with VTA upstream inputs prevented stress-induced increase in synaptic firing and anxiety.</p><p><strong>Conclusions: </strong>Potentiation of VTA inputs increased synaptic integration, thereby enhancing amygdala activity and promoting maladaptive anxiety. Understanding the impact of amygdala hyperactivity may lead to targeted therapies that restore circuit balance and offer new precision medicine approaches for anxiety disorders.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956767","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":"Longitudinal Associations Between Greenspace Exposure, Structural Brain Development, and Mental Health and Academic Performance During Early Adolescence.","authors":"Qingyang Li, Sarah Whittle, Divyangana Rakesh","doi":"10.1016/j.biopsych.2025.03.026","DOIUrl":"10.1016/j.biopsych.2025.03.026","url":null,"abstract":"<p><strong>Background: </strong>Greenspace exposure is associated with positive mental health and academic outcomes. In this preregistered longitudinal study, we examined whether the influence of greenspace exposure on structural brain development partially explains these associations.</p><p><strong>Methods: </strong>We analyzed data from the ABCD (Adolescent Brain Cognitive Development) Study (n = 7102) to test the relationship between greenspace exposure at ages 9 to 10 years and brain structure 2 years later, as well as changes over time. We also tested whether brain structural development statistically mediated the associations of greenspace exposure with mental health and academic performance.</p><p><strong>Results: </strong>Higher greenspace exposure was associated with greater total surface area (SA) and cortical volume (CV); greater cortical thickness in temporal regions and the insula; lower thickness in the caudal middle frontal and superior frontal gyri; greater SA across several regions; and greater volume of the caudate nucleus, putamen, and nucleus accumbens. In analyses studying changes in brain structure over time, higher greenspace exposure was associated with greater growth of total SA, lower average thickness reduction, and reduced total CV growth as well as changes at the regional level. We also found significant indirect effects of the association of greenspace exposure with academic performance and mental health through both total and regional cortical structure.</p><p><strong>Conclusions: </strong>Greenspace exposure is linked to structural neurodevelopment, which in turn is associated with better mental health and academic achievement. Our findings underscore the importance of greenspace in supporting brain development and positive outcomes in children and adolescents.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969246","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}
Andrew H. Miller, Jennifer C. Felger, Ebrahim Haroon
{"title":"Designing Clinical Trials for an Inflammatory Subtype of Major Depressive Disorder","authors":"Andrew H. Miller, Jennifer C. Felger, Ebrahim Haroon","doi":"10.1016/j.biopsych.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.04.003","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"17 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849433","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":"Sex Differences in Influences of Life Events on Gray Matter Volume in Youth","authors":"Lisa Wiersch , Elvisha Dhamala","doi":"10.1016/j.biopsych.2025.02.105","DOIUrl":"10.1016/j.biopsych.2025.02.105","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 9","pages":"Pages S37-S38"},"PeriodicalIF":9.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799185","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}