Biological psychiatry global open science最新文献

{"title":"Complement C5a Receptor Signaling Alters Stress Responsiveness and Modulates Microglia Following Chronic Stress Exposure","authors":"Hsiao-Jou Cortina Chen ,&nbsp;Jereme G. Spiers ,&nbsp;Titaya Lerskiatiphanich ,&nbsp;Sandra E. Parker ,&nbsp;Nickolas A. Lavidis ,&nbsp;Jenny N. Fung ,&nbsp;Trent M. Woodruff ,&nbsp;John D. Lee","doi":"10.1016/j.bpsgos.2024.100306","DOIUrl":"10.1016/j.bpsgos.2024.100306","url":null,"abstract":"<div><h3>Background</h3><p>Accumulating evidence underscores the pivotal role of heightened inflammation in the pathophysiology of stress-related diseases, but the underlying mechanisms remain elusive. The complement system, a key effector of the innate immune system, produces the C5–cleaved activation product C5a upon activation, initiating inflammatory responses through the canonical C5a receptor 1 (C5aR1). While C5aR1 is expressed in stress-responsive brain regions, its role in stress responsiveness remains unknown.</p></div><div><h3>Methods</h3><p>To investigate C5a-C5aR1 signaling in stress responses, mice underwent acute and chronic stress paradigms. Circulating C5a levels and messenger RNA expression of C5aR1 in the hippocampus and adrenal gland were measured. C5aR1-deficient mice were used to elucidate the effects of disrupted C5a-C5aR1 signaling across behavioral, hormonal, metabolic, and inflammation parameters.</p></div><div><h3>Results</h3><p>Chronic restraint stress elevated circulating C5a levels while reducing C5aR1 messenger RNA expression in the hippocampus and adrenal gland. Notably, the absence of C5aR1 signaling enhanced adrenal sensitivity to adrenocorticotropic hormone, concurrently reducing pituitary adrenocorticotropic hormone production and enhancing the response to acute stress. C5aR1-deficient mice exhibited attenuated reductions in locomotor activity and body weight under chronic stress. Additionally, these mice displayed increased glucocorticoid receptor sensitivity and disrupted glucose and insulin homeostasis. Chronic stress induced an increase in C5aR1-expressing microglia in the hippocampus, a response mitigated in C5aR1-deficient mice.</p></div><div><h3>Conclusions</h3><p>C5a-C5aR1 signaling emerges as a key metabolic regulator during stress, suggesting that complement activation and dysfunctional C5aR1 signaling may contribute to neuroinflammatory phenotypes in stress-related disorders. The results advocate for further exploration of complement C5aR1 as a potential therapeutic target for stress-related conditions.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 3","pages":"Article 100306"},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000193/pdfft?md5=89f35819977dcab92fc7ad91573cc714&pid=1-s2.0-S2667174324000193-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140282257","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)00016-8","DOIUrl":"https://doi.org/10.1016/S2667-1743(24)00016-8","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 2","pages":"Article 100303"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000168/pdfft?md5=7ecdec12c83f82a66840b3044549899e&pid=1-s2.0-S2667174324000168-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133997","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)00014-4","DOIUrl":"https://doi.org/10.1016/S2667-1743(24)00014-4","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 2","pages":"Article 100301"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000144/pdfft?md5=a09f895c864cac67ac326243ca501361&pid=1-s2.0-S2667174324000144-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133883","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)00013-2","DOIUrl":"https://doi.org/10.1016/S2667-1743(24)00013-2","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 2","pages":"Article 100300"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000132/pdfft?md5=1bee3c315791f7719dec2247232ede84&pid=1-s2.0-S2667174324000132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133932","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":"A New Paradigm to Investigate the Neuroscience of Irritability in Youth","authors":"Hugo Martin,&nbsp;Neir Eshel","doi":"10.1016/j.bpsgos.2024.100288","DOIUrl":"https://doi.org/10.1016/j.bpsgos.2024.100288","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 2","pages":"Article 100288"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000016/pdfft?md5=7e220e906998e897ea63cb71bcf0e3b2&pid=1-s2.0-S2667174324000016-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134195","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":"Making Sense of Sex in Neuroscience","authors":"Birgit Derntl ,&nbsp;Steffen R. Hage ,&nbsp;Manfred Hallschmid","doi":"10.1016/j.bpsgos.2024.100292","DOIUrl":"https://doi.org/10.1016/j.bpsgos.2024.100292","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 2","pages":"Article 100292"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000053/pdfft?md5=c573e419b3ab6337c23720a71787b00f&pid=1-s2.0-S2667174324000053-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134194","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":"The Impact of Maternal Inflammatory Conditions During Pregnancy on the Risk of Autism: Methodological Challenges","authors":"Ali S. Khashan ,&nbsp;Gerard W. O’Keeffe","doi":"10.1016/j.bpsgos.2023.100287","DOIUrl":"https://doi.org/10.1016/j.bpsgos.2023.100287","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 2","pages":"Article 100287"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174323001726/pdfft?md5=10d0a0e5afb8ee8cad4aa68bc53999ed&pid=1-s2.0-S2667174323001726-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133999","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":"Integrating Electronic Health Records and Polygenic Risk to Identify Genetically Unrelated Comorbidities of Schizophrenia That May Be Modifiable","authors":"Tess Vessels ,&nbsp;Nicholas Strayer ,&nbsp;Hyunjoon Lee ,&nbsp;Karmel W. Choi ,&nbsp;Siwei Zhang ,&nbsp;Lide Han ,&nbsp;Theodore J. Morley ,&nbsp;Jordan W. Smoller ,&nbsp;Yaomin Xu ,&nbsp;Douglas M. Ruderfer","doi":"10.1016/j.bpsgos.2024.100297","DOIUrl":"10.1016/j.bpsgos.2024.100297","url":null,"abstract":"<div><h3>Background</h3><p>Patients with schizophrenia have substantial comorbidity that contributes to reduced life expectancy of 10 to 20 years. Identifying modifiable comorbidities could improve rates of premature mortality. Conditions that frequently co-occur but lack shared genetic risk with schizophrenia are more likely to be products of treatment, behavior, or environmental factors and therefore are enriched for potentially modifiable associations.</p></div><div><h3>Methods</h3><p>Phenome-wide comorbidity was calculated from electronic health records of 250,000 patients across 2 independent health care institutions (Vanderbilt University Medical Center and Mass General Brigham); associations with schizophrenia polygenic risk scores were calculated across the same phenotypes in linked biobanks.</p></div><div><h3>Results</h3><p>Schizophrenia comorbidity was significantly correlated across institutions (<em>r</em> = 0.85), and the 77 identified comorbidities were consistent with prior literature. Overall, comorbidity and polygenic risk score associations were significantly correlated (<em>r</em> = 0.55, <em>p</em> = 1.29 × 10⁻¹¹⁸). However, directly testing for the absence of genetic effects identified 36 comorbidities that had significantly equivalent schizophrenia polygenic risk score distributions between cases and controls. This set included phenotypes known to be consequences of antipsychotic medications (e.g., movement disorders) or of the disease such as reduced hygiene (e.g., diseases of the nail), thereby validating the approach. It also highlighted phenotypes with less clear causal relationships and minimal genetic effects such as tobacco use disorder and diabetes.</p></div><div><h3>Conclusions</h3><p>This work demonstrates the consistency and robustness of electronic health record–based schizophrenia comorbidities across independent institutions and with the existing literature. It identifies known and novel comorbidities with an absence of shared genetic risk, indicating other causes that may be modifiable and where further study of causal pathways could improve outcomes for patients.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 3","pages":"Article 100297"},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000107/pdfft?md5=c033a311509e9f9e0e277600ed5a76e3&pid=1-s2.0-S2667174324000107-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140468248","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":"Bipolar Patient–Specific In Vitro Diagnostic Test Reveals Underlying Cardiac Arrhythmia Phenotype Caused by Calcium Channel Genetic Risk Factor","authors":"Rachel Dow ,&nbsp;Cindy DeLong ,&nbsp;Guihua Jiang ,&nbsp;Durga Attili ,&nbsp;Jeffery Creech ,&nbsp;Rachel Kraan ,&nbsp;Katherine Campbell ,&nbsp;Prakaimuk Saraithong ,&nbsp;Sue O’Shea ,&nbsp;Andre Monteiro da Rocha ,&nbsp;Melvin G. McInnis ,&nbsp;Todd J. Herron","doi":"10.1016/j.bpsgos.2024.100296","DOIUrl":"10.1016/j.bpsgos.2024.100296","url":null,"abstract":"<div><p>A common genetic risk factor for bipolar disorder is <em>CACNA1C</em>, a gene that is also critical for cardiac rhythm. The impact of <em>CACNA1C</em> mutations on bipolar patient cardiac rhythm is unknown. Here, we report the cardiac electrophysiological implications of a bipolar disorder–associated genetic risk factor in <em>CACNA1C</em> using patient induced pluripotent stem cell-derived cardiomyocytes. Results indicate that the <em>CACNA1C</em> bipolar disorder–related mutation causes cardiac electrical impulse conduction slowing mediated by impaired intercellular coupling via connexin 43 gap junctions. In vitro gene therapy to restore connexin 43 expression increased cardiac electrical impulse conduction velocity and protected against thioridazine-induced QT prolongation. Patients positive for bipolar disorder <em>CACNA1C</em> genetic risk factors may have elevated proarrhythmic risk for adverse events in response to psychiatric medications that slow conduction or prolong the QT interval. This in vitro diagnostic tool enables cardiac testing specific to patients with psychiatric disorders to determine their sensitivity to off-target effects of psychiatric medications.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 3","pages":"Article 100296"},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000090/pdfft?md5=efafaa8f782f1926f04d035280bbeeff&pid=1-s2.0-S2667174324000090-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965958","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":"Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell","authors":"Andrew D. Chapp ,&nbsp;Chinonso A. Nwakama ,&nbsp;Pramit P. Jagtap ,&nbsp;Chau-Mi H. Phan ,&nbsp;Mark J. Thomas ,&nbsp;Paul G. Mermelstein","doi":"10.1016/j.bpsgos.2024.100295","DOIUrl":"https://doi.org/10.1016/j.bpsgos.2024.100295","url":null,"abstract":"<div><h3>Background</h3><p>Cocaine-induced plasticity in the nucleus accumbens shell of males occurs primarily in dopamine D₁ receptor–expressing medium spiny neurons (D1R-MSNs), with little if any impact on dopamine D₂ receptor–expressing medium spiny neurons (D2R-MSNs). In females, the effect of cocaine on accumbens shell D1R- and D2R-MSN neurophysiology has yet to be reported, nor have estrous cycle effects been accounted for.</p></div><div><h3>Methods</h3><p>We used a 5-day locomotor sensitization paradigm followed by a 10- to 14-day drug-free abstinence period. We then obtained ex vivo whole-cell recordings from fluorescently labeled D1R-MSNs and D2R-MSNs in the nucleus accumbens shell of male and female mice during estrus and diestrus. We examined accumbens shell neuronal excitability as well as miniature excitatory postsynaptic currents (mEPSCs).</p></div><div><h3>Results</h3><p>In females, we observed alterations in D1R-MSN excitability across the estrous cycle similar in magnitude to the effects of cocaine in males. Furthermore, cocaine shifted estrous cycle–dependent plasticity from intrinsic excitability changes in D1R-MSNs to D2R-MSNs. In males, cocaine treatment produced the anticipated drop in D1R-MSN excitability with no effect on D2R-MSN excitability. Cocaine increased mEPSC frequencies and amplitudes in D2R-MSNs from females in estrus and mEPSC amplitudes of D2R-MSNs from females in diestrus. In males, cocaine increased both D1R- and D2R-MSN mEPSC amplitudes with no effect on mEPSC frequencies.</p></div><div><h3>Conclusions</h3><p>Overall, while there are similar cocaine-induced disparities regarding the relative excitability of D1R-MSNs versus D2R-MSNs between the sexes, this is mediated through reduced D1R-MSN excitability in males, whereas it is due to heightened D2R-MSN excitability in females.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 3","pages":"Article 100295"},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000089/pdfft?md5=ab53cdf1ae3a7cb4ed87a063dbc49a49&pid=1-s2.0-S2667174324000089-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140160240","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}