Complex psychiatry最新文献

{"title":"Hyperarousal Symptom Severity in Women with Posttraumatic Stress Disorder Might Be Associated with LINE-1 Hypomethylation in Childhood Sexual Abuse Victims.","authors":"Carolina Muniz Carvalho, Bruno Messina Coimbra, Amanda Bugiga, Diogo Ferri Marques, Vanessa Kiyomi Ota, Andrea Feijó Mello, Marcelo Feijó Mello, Sintia Iole Belangero","doi":"10.1159/000529698","DOIUrl":"10.1159/000529698","url":null,"abstract":"<p><strong>Introduction: </strong>Sexual assault and a history of childhood sexual abuse (CSA) are related to posttraumatic stress disorder (PTSD) development. Long interspersed nuclear elements (LINE-1) are transposable elements, and their methylation is used to infer DNA global methylation. DNA methylation can be affected by trauma exposition which in turn would be associated with PTSD. Thus, we investigated if the LINE-1 methylation pattern is related to PTSD symptoms in females with a history of CSA.</p><p><strong>Methods: </strong>This is a case-control study that examined, at baseline (W1), 64 women victims of sexual assault diagnosed with PTSD and 31 patients with PTSD who completed the 1-year follow-up (W2). Participants were categorized into two groups according to the presence of CSA (PTSDCSA+: NW1 = 19, NW2 = 10; PTSDCSA-: NW1 = 45, NW2 = 21). PTSD symptoms (re-experiencing, avoidance, hyperarousal, alterations in cognition/mood) were assessed using the Clinician-Administered PTSD Scale, and the history of CSA was assessed by the Childhood Trauma Questionnaire. LINE-1 methylation was measured in three sites (CpG1, CpG2, CpG3) located in the 5'UTR region using bisulfite conversion followed by pyrosequencing. Linear regression models were performed to test the relation between LINE-1 CpG sites methylation and PTSD symptoms.</p><p><strong>Results: </strong>We found a negative association between CpG2 methylation and hyperarousal symptoms among those in the PTSDCSA+ group in W1 (adjusted <i>p</i> = 0.003) compared to the PTSDCSA- group (<i>p</i> > 0.05). Still, no association was observed between other PTSD symptoms and other CpG sites. Further, in the longitudinal analysis, LINE-1 hypomethylation was no longer observed in PTSD participants exposed to CSA.</p><p><strong>Conclusion: </strong>Our findings suggest that LINE-1 methylation may help understand the relationship between trauma and PTSD. However, more studies are needed to investigate LINE-1 as an epigenetic marker of psychiatric disorders.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"9 1-4","pages":"44-56"},"PeriodicalIF":0.0,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10376526","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":"Prophylactic Efficacy of Riluzole against Anxiety- and Depressive-Like Behaviors in Two Rodent Stress Models.","authors":"Yashika Bansal, Corey Fee, Keith A Misquitta, Sierra A Codeluppi, Etienne Sibille, Robert M Berman, Vladimir Coric, Gerard Sanacora, Mounira Banasr","doi":"10.1159/000529534","DOIUrl":"10.1159/000529534","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic stress-related illnesses such as major depressive disorder and post-traumatic stress disorder share symptomatology, including anxiety, anhedonia, and helplessness. Across disorders, neurotoxic dysregulated glutamate (Glu) signaling may underlie symptom emergence. Current first-line antidepressant drugs, which do not directly target Glu signaling, fail to provide adequate benefit for many patients and are associated with high relapse rates. Riluzole modulates glutamatergic neurotransmission by increasing metabolic cycling and modulating signal transduction. Clinical studies exploring riluzole's efficacy in stress-related disorders have provided varied results. However, the utility of riluzole for treating specific symptom dimensions or as a prophylactic treatment has not been comprehensively assessed.</p><p><strong>Methods: </strong>We investigated whether chronic prophylactic riluzole (∼12-15 mg/kg/day p.o.) could prevent the emergence of behavioral deficits induced by unpredictable chronic mild stress (UCMS) in mice. We assessed (i) anxiety-like behavior using the elevated-plus maze, open-field test, and novelty-suppressed feeding, (ii) mixed anxiety/anhedonia-like behavior in the novelty-induced hypophagia test, and (iii) anhedonia-like behavior using the sucrose consumption test. Z-scoring summarized changes across tests measuring similar dimensions. In a separate learned helplessness (LH) cohort, we investigated whether chronic prophylactic riluzole treatment could block the development of helplessness-like behavior.</p><p><strong>Results: </strong>UCMS induced an elevation in anhedonia-like behavior and overall behavioral emotionality that was blocked by prophylactic riluzole. In the LH cohort, prophylactic riluzole blocked the development of helplessness-like behavior.</p><p><strong>Discussion/conclusion: </strong>This study supports the utility of riluzole as a prophylactic medication for preventing anhedonia and helplessness symptoms associated with stress-related disorders.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"9 1-4","pages":"57-69"},"PeriodicalIF":0.0,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9921371","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":"Cross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review.","authors":"Diana Leandra Núñez-Rios, José Jaime Martínez-Magaña, Sheila Tiemi Nagamatsu, John H Krystal, Karen G Martínez-González, Paola Giusti-Rodríguez, Janitza L Montalvo-Ortiz","doi":"10.1159/000529536","DOIUrl":"10.1159/000529536","url":null,"abstract":"<p><strong>Introduction: </strong>Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrated brain-specific molecular findings of PTSD from humans and animals.</p><p><strong>Methods: </strong>A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms.</p><p><strong>Results: </strong>Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, with 17 of them significantly enriched for PTSD. Chemical synaptic transmission and signaling by G-protein-coupled receptors were consistently enriched across omics and species.</p><p><strong>Discussion: </strong>Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD's pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"9 1-4","pages":"100-118"},"PeriodicalIF":0.0,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9928195","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":"Acknowledgement to Reviewers","authors":"","doi":"10.1159/000527923","DOIUrl":"https://doi.org/10.1159/000527923","url":null,"abstract":"<br />Complex Psychiatry 2022;8:100","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"254 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138505437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contents Vol. 8, 2022","authors":"","doi":"10.1159/000527924","DOIUrl":"https://doi.org/10.1159/000527924","url":null,"abstract":"","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"5 1","pages":"I - IV"},"PeriodicalIF":0.0,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81627067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front & Back Matter","authors":"","doi":"10.1159/000529262","DOIUrl":"https://doi.org/10.1159/000529262","url":null,"abstract":"","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80182127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic Contributions to Suicidal Thoughts and Behaviors in a Sample Ascertained for Alcohol Use Disorders.","authors":"Sarah M C Colbert, Niamh Mullins, Grace Chan, Jacquelyn L Meyers, Jessica Schulman, Samuel Kuperman, Dongbing Lai, John Nurnberger, Martin H Plawecki, Chella Kamarajan, Andrey P Anokhin, Kathleen K Bucholz, Victor Hesselbrock, Howard J Edenberg, John Kramer, Danielle M Dick, Bernice Porjesz, Arpana Agrawal, Emma C Johnson","doi":"10.1159/000529164","DOIUrl":"10.1159/000529164","url":null,"abstract":"<p><strong>Introduction: </strong>Suicidal thoughts and behaviors have partially distinct genetic etiologies.</p><p><strong>Methods: </strong>We used PRS-CS to create polygenic risk scores (PRSs) from GWAS of non-suicidal self-injury, broad-sense self-harm ideation, nonfatal suicide attempt, death by suicide, and depression. Using mixed-effect models, we estimated whether these PRSs were associated with a range of suicidal thoughts and behaviors in the Collaborative Study on the Genetics of Alcoholism (<i>N</i> = 7,526).</p><p><strong>Results: </strong>All PRSs were significantly associated with suicidal ideation and suicide attempt (betas = 0.08-0.44, false discovery rate [FDR] <0.023). All PRSs except non-suicidal self-injury PRS were associated with active suicidal ideation (betas = 0.14-0.22, FDR <0.003). Several associations remained significant in models where all significant PRSs were included as simultaneous predictors, and when all PRSs predicted suicide attempt, the PRS together explained 6.2% of the variance in suicide attempt. Significant associations were also observed between some PRSs and persistent suicidal ideation, non-suicidal self-injury, compounded suicide attempt, and desire to die.</p><p><strong>Conclusion: </strong>Our findings suggest that PRS for depression does not explain the entirety of the variance in suicidal thoughts and behaviors, with PRS specifically for suicidal thoughts and behaviors making additional and sometimes unique contributions.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"9 1-4","pages":"11-23"},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500364","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":"Large Common Mitochondrial DNA Deletions Are Associated with a Mitochondrial SNP T14798C Near the 3' Breakpoints.","authors":"Brooke E Hjelm,&nbsp;Christian Ramiro,&nbsp;Brandi L Rollins,&nbsp;Audrey A Omidsalar,&nbsp;Daniel S Gerke,&nbsp;Sujan C Das,&nbsp;Adolfo Sequeira,&nbsp;Ling Morgan,&nbsp;Alan F Schatzberg,&nbsp;Jack D Barchas,&nbsp;Francis S Lee,&nbsp;Richard M Myers,&nbsp;Stanley J Watson,&nbsp;Huda Akil,&nbsp;William E Bunney,&nbsp;Marquis P Vawter","doi":"10.1159/000528051","DOIUrl":"https://doi.org/10.1159/000528051","url":null,"abstract":"<p><strong>Introduction: </strong>Large somatic deletions of mitochondrial DNA (mtDNA) accumulate with aging in metabolically active tissues such as the brain. We have cataloged the breakpoints and frequencies of large mtDNA deletions in the human brain.</p><p><strong>Methods: </strong>We quantified 112 high-frequency mtDNA somatic deletions across four human brain regions with the Splice-Break2 pipeline. In addition, we utilized PLINK/Seq to test the association of mitochondrial genotypes with the abundance of these high-frequency mtDNA deletions. A conservative <i>p</i> value threshold of 5E-08 was used to find the significant loci.</p><p><strong>Results: </strong>One mtDNA SNP (T14798C) was significantly associated with mtDNA deletions in two brain regions, the dorsolateral prefrontal cortex (DLPFC) and the superior temporal gyrus. Since the DLPFC showed the most robust association between T14798C and two deletion breakpoints (7816-14807 and 5462-14807), this association was tested in the DLPFC of a replication sample and validated the first results. Incorporating the C allele at 14,798 bp increased the perfect/imperfect length of the repeat at the 3' breakpoint of the two associated deletions.</p><p><strong>Conclusion: </strong>This is the first study to identify the association of mtDNA SNP with large mtDNA deletions in the human brain. The T14798C allele located in the <i>MT-CYB</i> gene is a common polymorphism that occurs in several mitochondrial haplogroups. We hypothesize that the T14798C association with two deletions occurs by extending the repeat length around the 3' deletion breakpoints. This simple mechanism suggests that mtDNA SNPs can affect the mitochondrial genome structure, especially in brain where high levels of reactive oxygen species lead to deletion accumulation with aging.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"8 3-4","pages":"90-98"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a8/f0/cxp-0008-0090.PMC9909249.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9619693","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":"Sex Differences in Health Conditions Associated with Sexual Assault in a Large Hospital Population.","authors":"Allison M Lake, Slavina B Goleva, Lauren R Samuels, Laura M Carpenter, Lea K Davis","doi":"10.1159/000527363","DOIUrl":"10.1159/000527363","url":null,"abstract":"<p><strong>Introduction: </strong>Sexual assault is an urgent public health concern with both immediate and long-lasting health consequences, affecting 44% of women and 25% of men during their lifetimes. Large studies are needed to understand the unique healthcare needs of this patient population.</p><p><strong>Methods: </strong>We mined clinical notes to identify patients with a history of sexual assault in the electronic health record (EHR) at Vanderbilt University Medical Center (VUMC), a large university hospital in the Southeastern USA, from 1989 to 2021 (<i>N</i> = 3,376,424). Using a phenome-wide case-control study, we identified diagnoses co-occurring with disclosures of sexual assault. We performed interaction tests to examine whether sex modified any of these associations. Association analyses were restricted to a subset of patients receiving regular care at VUMC (<i>N</i> = 833,185).</p><p><strong>Results: </strong>The phenotyping approach identified 14,496 individuals (0.43%) across the VUMC-EHR with documentation of sexual assault and achieved a positive predictive value of 93.0% (95% confidence interval = 85.6-97.0%), determined by manual patient chart review. Out of 1,703 clinical diagnoses tested across all subgroup analyses, 465 were associated with sexual assault. Sex-by-trauma interaction analysis revealed 55 sex-differential associations and demonstrated increased odds of psychiatric diagnoses in male survivors.</p><p><strong>Discussion: </strong>This case-control study identified associations between disclosures of sexual assault and hundreds of health conditions, many of which demonstrated sex-differential effects. The findings of this study suggest that patients who have experienced sexual assault are at risk for developing wide-ranging medical and psychiatric comorbidities and that male survivors may be particularly vulnerable to developing mental illness.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"8 3-4","pages":"80-89"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/bc/cxp-0008-0080.PMC10288064.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9758531","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":"Inferring the Genetic Influences on Psychological Traits Using MRI Connectivity Predictive Models: Demonstration with Cognition.","authors":"Alexander S Hatoum, Andrew E Reineberg, Philip A Kragel, Tor D Wager, Naomi P Friedman","doi":"10.1159/000527224","DOIUrl":"10.1159/000527224","url":null,"abstract":"<p><strong>Introduction: </strong>Genetic correlations between brain and behavioral phenotypes in analyses from major genetic consortia have been weak and mostly nonsignificant. fMRI models of systems-level brain patterns may help improve our ability to link genes, brains, and behavior by identifying reliable and reproducible endophenotypes. Work using connectivity-based predictive modeling has generated brain-based proxies of behavioral and neuropsychological variables. If such models capture activity in inherited brain systems, they may offer a more powerful link between genes and behavior.</p><p><strong>Method: </strong>As a proof of concept, we develop models predicting intelligence (IQ) based on fMRI connectivity and test their effectiveness as endophenotypes. We link brain and IQ in a model development dataset of <i>N</i> = 3,000 individuals and test the genetic correlations between brain models and measured IQ in a genetic validation sample of <i>N</i> = 13,092 individuals from the UK Biobank. We compare an additive connectivity-based model to multivariate LASSO and ridge models phenotypically and genetically. We also compare these approaches to single \"candidate\" brain areas.</p><p><strong>Results: </strong>We found that predictive brain models were significantly phenotypically correlated with IQ and showed much stronger correlations than individual edges. Further, brain models were more heritable (h2 = 0.155-0.181) than single brain regions (h2 = 0.038-0.118) and captured about half of the genetic variance in IQ (rG = 0.422-0.576), while rGs with single brain measures were smaller and nonsignificant. For the different approaches, LASSO and ridge were similarly predictive, with slightly weaker performance of the additive model. LASSO model weights were highly theoretically interpretable and replicated known brain IQ associations. Finally, functional connectivity models trained in midlife showed genetic correlations with early life correlates of IQ, suggesting some stability in the prediction of fMRI models.</p><p><strong>Conclusion: </strong>Multisystem predictive models hold promise as imaging endophenotypes that offer complex and theoretically relevant conclusions for future imaging genetics research.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"8 3-4","pages":"63-79"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080187/pdf/cxp-0008-0063.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9916752","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}