{"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, 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}
Birgit Derntl , Steffen R. Hage , Manfred Hallschmid
{"title":"Making Sense of Sex in Neuroscience","authors":"Birgit Derntl , Steffen R. Hage , 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 , 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}
Tess Vessels , Nicholas Strayer , Hyunjoon Lee , Karmel W. Choi , Siwei Zhang , Lide Han , Theodore J. Morley , Jordan W. Smoller , Yaomin Xu , Douglas M. Ruderfer
{"title":"Integrating Electronic Health Records and Polygenic Risk to Identify Genetically Unrelated Comorbidities of Schizophrenia That May Be Modifiable","authors":"Tess Vessels , Nicholas Strayer , Hyunjoon Lee , Karmel W. Choi , Siwei Zhang , Lide Han , Theodore J. Morley , Jordan W. Smoller , Yaomin Xu , 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<sup>−118</sup>). 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}
Rachel Dow , Cindy DeLong , Guihua Jiang , Durga Attili , Jeffery Creech , Rachel Kraan , Katherine Campbell , Prakaimuk Saraithong , Sue O’Shea , Andre Monteiro da Rocha , Melvin G. McInnis , Todd J. Herron
{"title":"Bipolar Patient–Specific In Vitro Diagnostic Test Reveals Underlying Cardiac Arrhythmia Phenotype Caused by Calcium Channel Genetic Risk Factor","authors":"Rachel Dow , Cindy DeLong , Guihua Jiang , Durga Attili , Jeffery Creech , Rachel Kraan , Katherine Campbell , Prakaimuk Saraithong , Sue O’Shea , Andre Monteiro da Rocha , Melvin G. McInnis , 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}
Andrew D. Chapp , Chinonso A. Nwakama , Pramit P. Jagtap , Chau-Mi H. Phan , Mark J. Thomas , Paul G. Mermelstein
{"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 , Chinonso A. Nwakama , Pramit P. Jagtap , Chau-Mi H. Phan , Mark J. Thomas , 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 D<sub>1</sub> receptor–expressing medium spiny neurons (D1R-MSNs), with little if any impact on dopamine D<sub>2</sub> 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}
{"title":"Assessing the Role of Cortisol in Anxiety, Major Depression, and Neuroticism: A Mendelian Randomization Study Using SERPINA6/SERPINA1 Variants","authors":"Io Ieong Chan , Anise M.S. Wu","doi":"10.1016/j.bpsgos.2024.100294","DOIUrl":"10.1016/j.bpsgos.2024.100294","url":null,"abstract":"<div><h3>Background</h3><p>Previous evidence informed by the toxic stress model suggests that higher cortisol causes anxiety and major depression, but clinical success is lacking. To clarify the role of cortisol, we used Mendelian randomization to estimate its associations with anxiety, major depression, and neuroticism, leveraging the largest available genome-wide association studies including from the Psychiatric Genomics Consortium, the UK Biobank, and FinnGen.</p></div><div><h3>Methods</h3><p>After meta-analyzing 2 genome-wide association studies on morning plasma cortisol (<em>n</em> = 32,981), we selected single nucleotide polymorphisms (SNPs) at <em>p</em> < 5 × 10<sup>−8</sup> and <em>r</em><sup>2</sup> < 0.3 in the <em>SERPINA6/SERPINA1</em> gene region encoding proteins that influence cortisol bioavailability. We applied these SNPs to summary genetic associations with the outcomes considered (<em>n</em> = 17,310–449,484), and systolic blood pressure as a positive outcome, using inverse-variance weighted meta-analysis accounting for correlation. Sensitivity analyses addressing SNP correlation and confounding by childhood maltreatment and follow-up analyses using only SNPs that colocalized with <em>SERPINA6</em> expression were conducted.</p></div><div><h3>Results</h3><p>Cortisol was associated with anxiety (pooled odds ratio [OR] 1.16 per cortisol <em>z</em> score; 95% CI, 1.04 to 1.31), but not major depression (pooled OR 1.02, 95% CI, 0.95 to 1.10) or neuroticism (β −0.025; 95% CI, −0.071 to 0.022). Sensitivity analyses yielded similar estimates. Cortisol was positively associated with systolic blood pressure, as expected. Using rs9989237 and rs2736898, selected using colocalization, cortisol was associated with anxiety in the UK Biobank (OR 1.32; 95% CI, 1.01 to 1.74) but not with major depression in FinnGen (OR 1.14; 95% CI, 0.95 to 1.37).</p></div><div><h3>Conclusions</h3><p>Cortisol was associated with anxiety and may be a potential target for prevention. Other targets may be more relevant to major depression and neuroticism.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 3","pages":"Article 100294"},"PeriodicalIF":0.0,"publicationDate":"2024-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000077/pdfft?md5=f850bc31a412ddc0176a4934498b0c51&pid=1-s2.0-S2667174324000077-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139967099","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}
Taylor R. Thomas , Ashton J. Tener , Amy M. Pearlman , Katherine L. Imborek , Ji Seung Yang , John F. Strang , Jacob J. Michaelson
{"title":"Polygenic Scores Clarify the Relationship Between Mental Health and Gender Diversity","authors":"Taylor R. Thomas , Ashton J. Tener , Amy M. Pearlman , Katherine L. Imborek , Ji Seung Yang , John F. Strang , Jacob J. Michaelson","doi":"10.1016/j.bpsgos.2024.100291","DOIUrl":"10.1016/j.bpsgos.2024.100291","url":null,"abstract":"<div><h3>Background</h3><p>Gender-diverse individuals are at increased risk for mental health problems, but it is unclear whether this is due to shared environmental or genetic factors.</p></div><div><h3>Methods</h3><p>In two SPARK samples, we tested for associations of 16 polygenic scores (PGSs) with quantitative measures of gender diversity and mental health. In study 1, 639 independent adults (59% autistic) reported their mental health with the Adult Self-Report and their gender diversity with the Gender Self-Report (GSR). The GSR has 2 dimensions: binary (degree of identification with the gender opposite that implied by sex designated at birth) and nonbinary (degree of identification with a gender that is neither male nor female). In study 2 (<em>N</em> = 5165), we used a categorical measure of gender identity.</p></div><div><h3>Results</h3><p>In study 1, neuropsychiatric PGSs were positively associated with Adult Self-Report scores: externalizing was positively associated with the attention-deficit/hyperactivity disorder PGS (β = 0.10 [0.03–0.17]), and internalizing was positively associated with the PGSs for depression (β = 0.07 [0–0.14]) and neuroticism (β = 0.10 [0.03–0.17]). Interestingly, GSR scores were not significantly associated with any neuropsychiatric PGS. However, GSR nonbinary was positively associated with the cognitive performance PGS (β = 0.11 [0.05–0.18]), with the effect size comparable in magnitude to the associations of the neuropsychiatric PGSs with the Adult Self-Report. Additionally, GSR binary was positively associated with the nonheterosexual sexual behavior PGS (β = 0.07 [0–0.14]). In study 2, the cognitive performance PGS effect replicated; transgender and nonbinary individuals had higher PGSs (<em>t</em><sub>316</sub> = 4.16).</p></div><div><h3>Conclusions</h3><p>We showed that while gender diversity is phenotypically positively associated with mental health problems, the strongest PGS associations with gender diversity were with the cognitive performance PGS, not the neuropsychiatric PGSs.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 2","pages":"Article 100291"},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000041/pdfft?md5=8cb5777d1aa0db77332dda811c631d25&pid=1-s2.0-S2667174324000041-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139636450","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}