Biological psychiatry global open science最新文献

{"title":"GABA/Glutamate Neuron Differentiation Imbalance and Increased AKT/mTOR Signaling in CNTNAP2^-/- Cerebral Organoids.","authors":"Kleanthi Chalkiadaki, Elpida Statoulla, Maria Zafeiri, Georgia Voudouri, Theoklitos Amvrosiadis, Alexandra Typou, Niki Theodoridou, Dimitrios Moschovas, Apostolos Avgeropoulos, Martina Samiotaki, John O Mason, Christos G Gkogkas","doi":"10.1016/j.bpsgos.2024.100413","DOIUrl":"https://doi.org/10.1016/j.bpsgos.2024.100413","url":null,"abstract":"<p><strong>Background: </strong>The polygenic nature of autism spectrum disorder (ASD) requires the identification of converging genetic pathways during early development to elucidate its complexity and varied manifestations.</p><p><strong>Methods: </strong>We developed a human cerebral organoid model from induced pluripotent stem cells with targeted genome editing to abolish protein expression of the <i>CNTNAP2</i> ASD risk gene.</p><p><strong>Results: </strong>CNTNAP2^-/- cerebral organoids displayed accelerated cell cycle, ventricular zone disorganization, and increased cortical folding. Proteomic analysis revealed disruptions in glutamatergic/GABAergic (gamma-aminobutyric acidergic) synaptic pathways and neurodevelopment, and transcriptomic analysis revealed differentially expressed genes belonging to inhibitory neuron-related gene networks. Interestingly, there was a weak correlation between the 2 datasets, suggesting nuanced translational control mechanisms. Along these lines, we found upregulated AKT/mTOR (mechanistic target of rapamycin) signaling in CNTNAP2^-/- organoids. Spatial transcriptomic analysis of CNTNAP2^-/- ventricular-like zones demonstrated pervasive changes in gene expression, implicating upregulation of cell cycle regulation, synaptic, and glutamatergic/GABAergic pathways. We noted significant overlap of all day-30 organoid omics datasets differentially expressed genes from idiopathic ASD (macrocephaly) induced pluripotent stem cell-derived telencephalic organoids, where FOXG1 was upregulated. Moreover, we detected increased GAD1-expressing and decreased TBR1-expressing cells, suggesting altered GABAergic/glutamatergic neuron development.</p><p><strong>Conclusions: </strong>These findings potentially highlight a shared mechanism in the early cortical development of various forms of ASD, further elucidate the role of CNTNAP2 in ASD pathophysiology and cortical development, and pave the way for targeted therapies that use cerebral organoids as preclinical models.</p>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"100413"},"PeriodicalIF":4.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In This Issue – November","authors":"","doi":"10.1016/j.bpsgos.2024.100403","DOIUrl":"10.1016/j.bpsgos.2024.100403","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100403"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guide for Authors","authors":"","doi":"10.1016/S2667-1743(24)00123-X","DOIUrl":"10.1016/S2667-1743(24)00123-X","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100410"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subscribers Page","authors":"","doi":"10.1016/S2667-1743(24)00121-6","DOIUrl":"10.1016/S2667-1743(24)00121-6","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100408"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Board Page","authors":"","doi":"10.1016/S2667-1743(24)00120-4","DOIUrl":"10.1016/S2667-1743(24)00120-4","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100407"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgments","authors":"","doi":"10.1016/j.bpsgos.2024.100404","DOIUrl":"10.1016/j.bpsgos.2024.100404","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100404"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticotropin-Releasing Factor Modulates Binge-Like Ethanol Drinking in a Sex-Dependent Manner: Impact of Amygdala Deletion and Inhibition of a Central Amygdala to Lateral Hypothalamus Circuit","authors":"Sophie C. Bendrath ,&nbsp;Hernán G. Méndez ,&nbsp;Anne M. Dankert ,&nbsp;Jose Manuel Lerma-Cabrera ,&nbsp;Francisca Carvajal ,&nbsp;Ana Paula S. Dornellas ,&nbsp;Sophia Lee ,&nbsp;Sofia Neira ,&nbsp;Harold Haun ,&nbsp;Eric Delpire ,&nbsp;Montserrat Navarro ,&nbsp;Thomas L. Kash ,&nbsp;Todd E. Thiele","doi":"10.1016/j.bpsgos.2024.100405","DOIUrl":"10.1016/j.bpsgos.2024.100405","url":null,"abstract":"<div><h3>Background</h3><div>Binge alcohol drinking is a dangerous behavior that can contribute to the development of more severe alcohol use disorder. Importantly, the rate and severity of alcohol use disorder has historically differed between men and women, suggesting that there may be sex differences in the central mechanisms that modulate alcohol (ethanol) consumption. Corticotropin-releasing factor (CRF) is a centrally expressed neuropeptide that has been implicated in the modulation of binge-like ethanol intake, and emerging data highlight sex differences in CRF systems.</div></div><div><h3>Methods</h3><div>In the current report, we characterized CRF+ neurocircuitry arising from the central nucleus of the amygdala (CeA) and innervating the lateral hypothalamus (LH) in the modulation of binge-like ethanol intake in male and female mice.</div></div><div><h3>Results</h3><div>Using chemogenetic tools, we found that silencing the CRF+ CeA to LH circuit significantly blunted binge-like ethanol intake in male but not female mice. Consistently, genetic deletion of CRF from neurons of the CeA blunted ethanol intake exclusively in male mice. Furthermore, pharmacological blockade of the CRF₁ receptor in the LH significantly reduced binge-like ethanol intake in male mice only, while CRF₂ receptor activation in the LH failed to alter ethanol intake in either sex. Finally, a history of binge-like ethanol drinking reduced <em>C</em><em>rf</em> messenger RNA levels in the CeA regardless of sex.</div></div><div><h3>Conclusions</h3><div>These observations provide novel evidence that CRF+ CeA to LH neurocircuitry is more sensitive for modulating binge-like ethanol intake in male mice, which may provide insight into the mechanisms that guide known sex differences in binge-like ethanol intake.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100405"},"PeriodicalIF":4.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding Depth of Meditation: Electroencephalography Insights From Expert Vipassana Practitioners","authors":"Nicco Reggente ,&nbsp;Christian Kothe ,&nbsp;Tracy Brandmeyer ,&nbsp;Grant Hanada ,&nbsp;Ninette Simonian ,&nbsp;Sean Mullen ,&nbsp;Tim Mullen","doi":"10.1016/j.bpsgos.2024.100402","DOIUrl":"10.1016/j.bpsgos.2024.100402","url":null,"abstract":"<div><h3>Background</h3><div>Meditation practices have demonstrated numerous psychological and physiological benefits, but capturing the neural correlates of varying meditative depths remains challenging. In this study, we aimed to decode self-reported time-varying meditative depth in expert practitioners using electroencephalography (EEG).</div></div><div><h3>Methods</h3><div>Expert Vipassana meditators (<em>n</em> = 34) participated in 2 separate sessions. Participants reported their meditative depth on a personally defined 1 to 5 scale using both traditional probing and a novel spontaneous emergence method. EEG activity and effective connectivity in theta, alpha, and gamma bands were used to predict meditative depth using machine/deep learning, including a novel method that fused source activity and connectivity information.</div></div><div><h3>Results</h3><div>We achieved significant accuracy in decoding self-reported meditative depth across unseen sessions. The spontaneous emergence method yielded improved decoding performance compared with traditional probing and correlated more strongly with postsession outcome measures. Best performance was achieved by a novel machine learning method that fused spatial, spectral, and connectivity information. Conventional EEG channel-level methods and preselected default mode network regions fell short in capturing the complex neural dynamics associated with varying meditation depths.</div></div><div><h3>Conclusions</h3><div>This study demonstrates the feasibility of decoding personally defined meditative depth using EEG. The findings highlight the complex, multivariate nature of neural activity during meditation and introduce spontaneous emergence as an ecologically valid and less obtrusive experiential sampling method. These results have implications for advancing neurofeedback techniques and enhancing our understanding of meditative practices.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100402"},"PeriodicalIF":4.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychobiological Stress Response Profiles in Current and Remitted Depression: A Person-Centered, Multisystem Approach","authors":"Manuel Kuhn ,&nbsp;David C. Steinberger ,&nbsp;Jason José Bendezú ,&nbsp;Maria Ironside ,&nbsp;Min S. Kang ,&nbsp;Kaylee E. Null ,&nbsp;Devon L. Brunner ,&nbsp;Diego A. Pizzagalli","doi":"10.1016/j.bpsgos.2024.100400","DOIUrl":"10.1016/j.bpsgos.2024.100400","url":null,"abstract":"<div><h3>Background</h3><div>A dysregulated stress response, including exaggerated affective reactivity and abnormal hypothalamic-pituitary-adrenal axis responsivity, has been implicated in the etiology, maintenance, and relapse of major depressive disorder (MDD). Among adolescents, discordant affective and physiological stress response profiles have been linked to negative affective outcomes and increased risk for psychopathology. Whether these findings extend to adults with varying degree of MDD risk is unclear, as are possible links to various risk factors.</div></div><div><h3>Methods</h3><div>We used a person-centered, multisystem approach in a sample of 119 unmedicated adults with current or remitted MDD and individuals without past MDD to evaluate psychobiological stress response profiles. Multitrajectory modeling was applied to positive affect, negative affect, and salivary cortisol (CORT) levels in response to the Maastricht Acute Stress Test.</div></div><div><h3>Results</h3><div>Analyses identified 4 within-person profiles, 1 typical, termed normative (<em>n</em> = 32, 26.9%) and 3 atypical: CORT hyperreactivity affective stability (<em>n</em> = 17, 14.3%), CORT hyporeactivity affective reactivity 1 (<em>n</em> = 45, 37.8%), and CORT hyporeactivity affective reactivity 2 (<em>n</em> = 25, 21.0%). While validating the assumption of a normative profile and increased risk for psychopathology in non-normative stress response profiles, coherent associations emerged between stress response profiles and clinical status, depression severity, anhedonia, perceived stress, childhood adversity, and reports of well-being, suggesting increased risk for psychopathology for individuals with a hyperreactive or discordant hyporeactive stress response profile.</div></div><div><h3>Conclusions</h3><div>This work advances our understanding of stress response mechanisms in MDD and underscores the potential of targeted interventions to enhance resilience and reduce psychopathology based on individual stress response profiles.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100400"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142651667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidimensional Effects of Stress on Neuronal Exosome Levels and Simultaneous Transcriptomic Profiles.","authors":"Hope Kronman, Amarjyot Singh, Shofiul Azam, Andrea S Guzman, Danielle Zelli, Timothy Lau, Josh Dobbin, Benedetta Bigio, Carla Nasca","doi":"10.1016/j.bpsgos.2024.100401","DOIUrl":"10.1016/j.bpsgos.2024.100401","url":null,"abstract":"<p><strong>Background: </strong>An excess of exosomes, nanovesicles released from all cells and key regulators of brain plasticity, is an emerging therapeutic target for stress-related mental illnesses. The effects of chronic stress on exosome levels are unknown; even less is known about molecular drivers of exosome levels in the stress response.</p><p><strong>Methods: </strong>We used our state-of-the-art protocol with 2 complementary strategies to isolate neuronal exosomes from plasma, ventral dentate gyrus, basolateral amygdala, and olfactory bulbs of male mice to determine the effects of chronic restraint stress (CRS) on exosome levels. Next, we used RNA sequencing and bioinformatic analyses to identify molecular drivers of exosome levels.</p><p><strong>Results: </strong>We found that CRS leads to an increase in the levels of neuronal exosomes but not total (i.e., not neuronally enriched) exosome levels assayed in plasma and the ventral dentate gyrus, whereas CRS leads to a decrease in neuronal exosome levels but not total exosome levels in the basolateral amygdala. There was a further specificity of effects as shown by a lack of changes in the levels of neuronal exosomes assayed in the olfactory bulbs. In pursuit of advancing translational applications, we showed that acetyl-L-carnitine administration restores the CRS-induced increase in neuronal exosome levels assayed in plasma (the most accessible specimen). Furthermore, the CRS-induced changes in neuronal exosome levels in the ventral dentate gyrus and basolateral amygdala mirrored the opposite pattern of CRS-induced transcriptional changes in these key brain areas, with β-estradiol signaling as a potential upstream driver of neuronal exosome levels.</p><p><strong>Conclusions: </strong>This study provides a foundation for future studies of new forms of local and distant communication in stress neurobiology by demonstrating specific relationships between neuronal exosome levels assayed in plasma and the brain and providing new candidate targets for the normalization of exosome levels.</p>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"100401"},"PeriodicalIF":4.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}