Complex psychiatryPub Date : 2022-09-15eCollection Date: 2023-01-01DOI: 10.1159/000527041
Keira J A Johnston, Laura M Huckins
{"title":"Chronic Pain and Psychiatric Conditions.","authors":"Keira J A Johnston, Laura M Huckins","doi":"10.1159/000527041","DOIUrl":"10.1159/000527041","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic pain is a common condition with high socioeconomic and public health burden. A wide range of psychiatric conditions are often comorbid with chronic pain and chronic pain conditions, negatively impacting successful treatment of either condition. The psychiatric condition receiving most attention in the past with regard to chronic pain comorbidity has been major depressive disorder, despite the fact that many other psychiatric conditions also demonstrate epidemiological and genetic overlap with chronic pain. Further understanding potential mechanisms involved in psychiatric and chronic pain comorbidity could lead to new treatment strategies both for each type of disorder in isolation and in scenarios of comorbidity.</p><p><strong>Methods: </strong>This article provides an overview of relationships between DSM-5 psychiatric diagnoses and chronic pain, with particular focus on PTSD, ADHD, and BPD, disorders which are less commonly studied in conjunction with chronic pain. We also discuss potential mechanisms that may drive comorbidity, and present new findings on the genetic overlap of chronic pain and ADHD, and chronic pain and BPD using linkage disequilibrium score regression analyses.</p><p><strong>Results: </strong>Almost all psychiatric conditions listed in the DSM-5 are associated with increased rates of chronic pain. ADHD and BPD are significantly genetically correlated with chronic pain. Psychiatric conditions aside from major depression are often under-researched with respect to their relationship with chronic pain.</p><p><strong>Conclusion: </strong>Further understanding relationships between psychiatric conditions other than major depression (such as ADHD, BPD, and PTSD as exemplified here) and chronic pain can positively impact understanding of these disorders, and treatment of both psychiatric conditions and chronic pain.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"9 1-4","pages":"24-43"},"PeriodicalIF":0.0,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080192/pdf/cxp-0009-0024.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9283663","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}
Complex psychiatryPub Date : 2022-09-15eCollection Date: 2023-01-01DOI: 10.1159/000527022
Laura M Huckins
{"title":"Thoughtful Phenotype Definitions Empower Participants and Power Studies.","authors":"Laura M Huckins","doi":"10.1159/000527022","DOIUrl":"10.1159/000527022","url":null,"abstract":"","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"8 3-4","pages":"57-62"},"PeriodicalIF":0.0,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080191/pdf/cxp-0008-0057.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10312621","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":"Alcohol Use and Use Disorder and Cancer Risk: Perspective on Causal Inference.","authors":"Hang Zhou, Vasilis Vasiliou","doi":"10.1159/000526407","DOIUrl":"https://doi.org/10.1159/000526407","url":null,"abstract":"<jats:p>None</jats:p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"8 1-2","pages":"9-12"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669948/pdf/cxp-0008-0009.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9162447","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}
Complex psychiatryPub Date : 2022-09-01Epub Date: 2022-02-28DOI: 10.1159/000523748
Darius M Bost, Chris Bizon, Jeffrey L Tilson, Dayne L Filer, Ian R Gizer, Kirk C Wilhelmsen
{"title":"Association of Predicted Expression and Multimodel Association Analysis of Substance Abuse Traits.","authors":"Darius M Bost, Chris Bizon, Jeffrey L Tilson, Dayne L Filer, Ian R Gizer, Kirk C Wilhelmsen","doi":"10.1159/000523748","DOIUrl":"10.1159/000523748","url":null,"abstract":"<p><strong>Introduction: </strong>Genome-wide association studies (GWAS) have played a critical role in identifying many thousands of loci associated with complex phenotypes and diseases. This has led to several translations of novel disease susceptibility genes into drug targets and care. This however has not been the case for analyses where sample sizes are small, which suffer from multiple comparisons testing. The present study examined the statistical impact of combining a burden test methodology, PrediXcan, with a multimodel meta-analysis, cross phenotype association (CPASSOC).</p><p><strong>Methods: </strong>The analysis was conducted on 5 addiction traits: family alcoholism, cannabis craving, alcohol, nicotine, and cannabis dependence and 10 brain tissues: anterior cingulate cortex BA24, cerebellar hemisphere, cortex, hippocampus, nucleus accumbens basal ganglia, caudate basal ganglia, cerebellum, frontal cortex BA9, hypothalamus, and putamen basal ganglia. Our sample consisted of 1,640 participants from the University of California, San Francisco (UCSF) Family Alcoholism Study. Genotypes were obtained through low pass whole genome sequencing and the use of Thunder, a linkage disequilibrium variant caller.</p><p><strong>Results: </strong>The post-PrediXcan, gene-phenotype association without aggregation resulted in 2 significant results, <i>HCG27</i> and <i>SPPL2B</i>. Aggregating across phenotypes resulted no significant findings. Aggregating across tissues resulted in 15 significant and 5 suggestive associations: <i>PPIE, RPL36AL, FOXN2, MTERF4, SEPTIN2, CIAO3, RPL36AL, ZNF304, CCDC66, SSPOP, SLC7A9, LY75, MTRF1L, COA5,</i> and <i>RRP7A</i>; <i>RPS23, GNMT, ERV3-1, APIP</i>, and <i>HLA-B,</i> respectively.</p><p><strong>Discussion: </strong>Given the relatively small size of the cohort, this multimodel approach was able to find over a dozen significant associations between predicted gene expression and addiction traits. Of our findings, 8 had prior associations with similar phenotypes through investigation of the GWAS Atlas. With the onset of improved transcriptome data, this approach should increase in efficacy.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":" ","pages":"35-46"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bc/99/cxp-0008-0035.PMC9669989.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40504231","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}
Complex psychiatryPub Date : 2022-09-01Epub Date: 2022-05-23DOI: 10.1159/000525079
Sevim B Bianchi, Alvin D Jeffery, David C Samuels, Lori Schirle, Abraham A Palmer, Sandra Sanchez-Roige
{"title":"Accelerating Opioid Use Disorders Research by Integrating Multiple Data Modalities.","authors":"Sevim B Bianchi, Alvin D Jeffery, David C Samuels, Lori Schirle, Abraham A Palmer, Sandra Sanchez-Roige","doi":"10.1159/000525079","DOIUrl":"10.1159/000525079","url":null,"abstract":"","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"8 1-2","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669996/pdf/cxp-0008-0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9998082","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}
Robin E Bonomi, Matthew Girgenti, John H Krystal, Kelly P Cosgrove
{"title":"A Role for Histone Deacetylases in the Biology and Treatment of Post-Traumatic Stress Disorder: What Do We Know and Where Do We Go from Here?","authors":"Robin E Bonomi, Matthew Girgenti, John H Krystal, Kelly P Cosgrove","doi":"10.1159/000524079","DOIUrl":"https://doi.org/10.1159/000524079","url":null,"abstract":"<p><p>Post-traumatic stress disorder is a prevalent disorder within the USA and worldwide with a yearly diagnosis rate of 2-4% and affecting women more than men. One of the primary methods for study of this stress disorder relies on animal models as there are few noninvasive methods and few replicated peripheral biomarkers for use in humans. One area of active research in psychiatric neuroscience is the field of epigenetics - how the chemical modifications of the genetic code regulate behavior. The dynamic changes in histone acetylation and deacetylation in the brain are not fully reflected by the study of peripheral biomarker. In this review, we aim to examine the role of histone acetylation and deacetylation in memory formation and fear memory learning. The studies discussed here focus largely on the role of histone deacetylases (HDACs) in animal models of trauma and fear response. Many studies used HDAC inhibitors to elucidate the effects after inhibition of these enzymes after trauma or stress. These studies of memory processing and cued fear extinction in animal can often shed light on human disorders of cued fear responses and memory dysregulation after stress or trauma such as in PTSD. These results provide strong evidence for a role of these enzymes in PTSD in humans. The few clinical studies that exist with HDAC inhibitors also suggest a fundamental role of these enzymes in the neurobiology of the stress response. Further study of these enzymes in both clinical and pre-clinical settings may help elucidate the neurobiology of stress-related pathology like PTSD and provide a foundation for novel therapy to treat these disorders.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"8 1-2","pages":"13-27"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669946/pdf/cxp-0008-0013.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9836160","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}
Complex psychiatryPub Date : 2022-09-01Epub Date: 2022-06-02DOI: 10.1159/000525313
Mariela V Jennings, Hyunjoon Lee, Daniel B Rocha, Sevim B Bianchi, Brandon J Coombes, Richard C Crist, Annika B Faucon, Yirui Hu, Rachel L Kember, Travis T Mallard, Maria Niarchou, Melissa N Poulsen, Peter Straub, Richard D Urman, Colin G Walsh, Lea K Davis, Jordan W Smoller, Vanessa Troiani, Sandra Sanchez-Roige
{"title":"Identifying High-Risk Comorbidities Associated with Opioid Use Patterns Using Electronic Health Record Prescription Data.","authors":"Mariela V Jennings, Hyunjoon Lee, Daniel B Rocha, Sevim B Bianchi, Brandon J Coombes, Richard C Crist, Annika B Faucon, Yirui Hu, Rachel L Kember, Travis T Mallard, Maria Niarchou, Melissa N Poulsen, Peter Straub, Richard D Urman, Colin G Walsh, Lea K Davis, Jordan W Smoller, Vanessa Troiani, Sandra Sanchez-Roige","doi":"10.1159/000525313","DOIUrl":"10.1159/000525313","url":null,"abstract":"<p><strong>Introduction: </strong>Opioid use disorders (OUDs) constitute a major public health issue, and we urgently need alternative methods for characterizing risk for OUD. Electronic health records (EHRs) are useful tools for understanding complex medical phenotypes but have been underutilized for OUD because of challenges related to underdiagnosis, binary diagnostic frameworks, and minimally characterized reference groups. As a first step in addressing these challenges, a new paradigm is warranted that characterizes risk for opioid prescription misuse on a continuous scale of severity, i.e., as a continuum.</p><p><strong>Methods: </strong>Across sites within the PsycheMERGE network, we extracted prescription opioid data and diagnoses that co-occur with OUD (including psychiatric and substance use disorders, pain-related diagnoses, HIV, and hepatitis C) for over 2.6 million patients across three health registries (Vanderbilt University Medical Center, Mass General Brigham, Geisinger) between 2005 and 2018. We defined three groups based on levels of opioid exposure: no prescriptions, minimal exposure, and chronic exposure and then compared the comorbidity profiles of these groups to the full registries and to those with OUD diagnostic codes.</p><p><strong>Results: </strong>Our results confirm that EHR data reflects known higher prevalence of substance use disorders, psychiatric disorders, medical, and pain diagnoses in patients with OUD diagnoses and chronic opioid use. Comorbidity profiles that distinguish opioid exposure are strikingly consistent across large health systems, indicating the phenotypes described in this new quantitative framework are robust to health systems differences.</p><p><strong>Conclusion: </strong>This work indicates that EHR prescription opioid data can serve as a platform to characterize complex risk markers for OUD using existing data.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"8 1-2","pages":"47-55"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669950/pdf/cxp-0008-0047.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9102124","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}
S. Colbert, N. Mullins, G. Chan, J. Meyers, Jessica Schulman, S. Kuperman, D. Lai, J. Nurnberger, M. Plawecki, C. Kamarajan, A. Anokhin, K. Bucholz, V. Hesselbrock, H. Edenberg, J. Kramer, D. Dick, B. Porjesz, A. Agrawal, E. Johnson
{"title":"Polygenic contributions to suicidal thoughts and behaviors in a sample ascertained for alcohol use disorders","authors":"S. Colbert, N. Mullins, G. Chan, J. Meyers, Jessica Schulman, S. Kuperman, D. Lai, J. Nurnberger, M. Plawecki, C. Kamarajan, A. Anokhin, K. Bucholz, V. Hesselbrock, H. Edenberg, J. Kramer, D. Dick, B. Porjesz, A. Agrawal, E. Johnson","doi":"10.1101/2022.08.18.22278943","DOIUrl":"https://doi.org/10.1101/2022.08.18.22278943","url":null,"abstract":"Suicidal thoughts and behaviors have partially distinct genetic etiologies. We used PRS-CS to create polygenic risk scores (PRS) from GWAS of non-suicidal self-injury, broad sense self-harm ideation, non-fatal suicide attempt, death by suicide, and depression. Using mixed-effect models, we estimated whether these PRS were associated with a range of suicidal thoughts and behaviors in the Collaborative Study on the Genetics of Alcoholism (N = 7,526). All PRS were significantly associated with suicidal ideation and suicide attempt (betas=0.08-0.44, FDR<0.023). All PRS except non-suicidal self-injury PRS were associated with active suicidal ideation and severity of suicidality (betas=0.04-0.22, FDR<0.034). Several associations remained significant in models where all significant PRS were included as simultaneous predictors, and when all PRS predicted suicide attempt, the PRS together explained 6.2% of the variance in suicide attempt. Significant associations were also observed between some PRS and persistent suicidal ideation, non-suicidal self-injury, attempt severity and desire to die. 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.","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83718752","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}
B. Schäfer, L. R. Gorjão, G. Yalcin, Ellen Förstner, Richard Jumar, H. Maass, U. Kühnapfel, V. Hagenmeyer
{"title":"Microscopic fluctuations in power-grid frequency recordings at the sub-second scale","authors":"B. Schäfer, L. R. Gorjão, G. Yalcin, Ellen Förstner, Richard Jumar, H. Maass, U. Kühnapfel, V. Hagenmeyer","doi":"10.48550/arXiv.2208.06379","DOIUrl":"https://doi.org/10.48550/arXiv.2208.06379","url":null,"abstract":"Complex systems, such as the power grid, are essential for our daily lives. Many\u0000 complex systems display multifractal behavior, correlated fluctuations and power\u0000 laws. Whether the power-grid frequency, an indicator of the balance of supply\u0000 and demand in the electricity grid, also displays such complexity remains a\u0000 mostly open question. Within the present article, we utilize highly resolved\u0000 measurements to quantify the properties of the power-grid frequency, making\u0000 three key contributions: First, we demonstrate the existence of power laws in\u0000 power-grid frequency measurements. Second, we show that below one second, the\u0000 dynamics may fundamentally change, including a suddenly increasing power\u0000 spectral density, emergence of multifractality and a change of correlation\u0000 behavior. Third, we provide a simplified stochastic model involving positively\u0000 correlated noise to reproduce the observed dynamics, possibly linked to\u0000 frequency-dependent loads. Finally, we stress the need for high-quality\u0000 measurements and discuss how we obtained the data analyzed here.","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"85 1","pages":"2657039:1-2657039:13"},"PeriodicalIF":0.0,"publicationDate":"2022-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89034115","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}