Complex psychiatryPub Date : 2023-03-29eCollection Date: 2023-01-01DOI: 10.1159/000530222
Morgan N Driver, Sally I-Chun Kuo, Jehannine Austin, Danielle M Dick
{"title":"Integrating Theory with Education about Genetic Risk for Alcohol Use Disorder: The Effects of a Brief Online Educational Tool on Elements of the Health Belief Model.","authors":"Morgan N Driver, Sally I-Chun Kuo, Jehannine Austin, Danielle M Dick","doi":"10.1159/000530222","DOIUrl":"10.1159/000530222","url":null,"abstract":"<p><strong>Introduction: </strong>The utility of genetic risk information relies on the assumption that individuals will use the information to change behavior to reduce risk of developing health problems. Educational interventions designed to target elements of the Health Belief Model have shown to be effective in promoting behaviors for positive outcomes.</p><p><strong>Methods: </strong>A randomized controlled trial (RCT) was conducted in 325 college students to assess whether a brief, online educational intervention altered elements of the Health Belief Model that are known to be associated with motivations and intentions to change behavior. The RCT included a control condition, an intervention condition that received information about alcohol use disorder (AUD), and an intervention condition that received information about polygenic risk scores and AUD. We used <i>t</i> tests and ANOVA methods to compare differences in beliefs related to the Health Belief Model across study conditions and demographic characteristics.</p><p><strong>Results: </strong>Providing educational information did not impact worry about developing AUD, perceived susceptibility and severity of developing alcohol problems, or perceived benefits and barriers of risk-reducing actions. Individuals in the condition that received educational information about polygenic risk scores and AUD reported higher perceived chance of developing AUD than individuals in the control condition (adj. <i>p</i> < 0.01). Sex, race/ethnicity, family history, and drinking status were associated with several components of the Health Belief Model.</p><p><strong>Conclusion: </strong>Findings from this study demonstrate the need to better design and refine the educational information intended to accompany the return of genetic feedback for AUD to better promote risk-reducing behaviors.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"9 1-4","pages":"89-99"},"PeriodicalIF":0.0,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9857806","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 : 2023-03-13eCollection Date: 2023-01-01DOI: 10.1159/000530120
Erin C Dunn, Daniel S Busso, Kathryn A Davis, Andrew D A C Smith, Colter Mitchell, Henning Tiemeier, Ezra S Susser
{"title":"Sensitive Periods for the Effect of Child Maltreatment on Psychopathology Symptoms in Adolescence.","authors":"Erin C Dunn, Daniel S Busso, Kathryn A Davis, Andrew D A C Smith, Colter Mitchell, Henning Tiemeier, Ezra S Susser","doi":"10.1159/000530120","DOIUrl":"10.1159/000530120","url":null,"abstract":"<p><strong>Introduction: </strong>Child maltreatment is among the strongest risk factors for mental disorders. However, little is known about whether there are ages when children may be especially vulnerable to its effects. We sought to identify potential sensitive periods when exposure to the 2 most common types of maltreatment (neglect and harsh physical discipline) had a particularly detrimental effect on youth mental health.</p><p><strong>Methods: </strong>Data came from the Future of Families and Child Wellbeing Study (FFCWS), a birth cohort oversampled from \"fragile families\" (<i>n</i> = 3,474). Maltreatment was assessed at 3, 5, and 9 years of age using an adapted version of the Parent-Child Conflict Tactics Scales (CTS-PC). Using least angle regression, we examined the relationship between repeated measures of exposure to maltreatment on psychopathology symptoms at age 15 years (Child Behavior Checklist; CBCL/6-18). For comparison, we evaluated the strength of evidence to support the existence of sensitive periods in relation to an accumulation of risk model.</p><p><strong>Results: </strong>We identified sensitive periods for harsh physical discipline, whereby psychopathology symptom scores were highest among girls exposed at age 9 years (<i>r</i><sup>2</sup> = 0.67 internalizing symptoms; <i>r</i><sup>2</sup> = 1% externalizing symptoms) and among boys exposed at age 5 years (<i>r</i><sup>2</sup> = 0.41%). However, for neglect, the accumulation of risk model explained more variability in psychopathology symptoms for both boys and girls.</p><p><strong>Conclusion: </strong>Child maltreatment may have differential effects based on the child's sex, type of exposure, and the age at which it occurs. These findings provide additional evidence for clinicians assessing the benefits and drawbacks of screening efforts and point toward possible mechanisms driving increased vulnerability to psychopathology.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"9 1-4","pages":"145-153"},"PeriodicalIF":0.0,"publicationDate":"2023-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415688","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 : 2023-02-21eCollection Date: 2023-01-01DOI: 10.1159/000529732
Hao Xuan Tan, Adam Md Kamal, Sivakumar Thurairajasingam, Maude Elvira Phipps
{"title":"Addressing Emotional Dysregulation and Potential Pharmacogenetic Implication of 5-HTTLPR Genotype in Attention Deficit Hyperactivity Disorder.","authors":"Hao Xuan Tan, Adam Md Kamal, Sivakumar Thurairajasingam, Maude Elvira Phipps","doi":"10.1159/000529732","DOIUrl":"10.1159/000529732","url":null,"abstract":"<p><strong>Background: </strong>This review unpacks the emotional presentation of externalizing behaviors in attention deficit hyperactivity disorder (ADHD), by diving into the psychophysiology, neurophysiology, and neurogenetics in relation to executive function. The correlations among these three variables are identified, showing that standard assessments for ADHD leave out the emotional dysregulation element. This may lead to suboptimal management outcomes during the developmental progression into adolescence and adulthood.</p><p><strong>Summary: </strong>The emotional impulsivity manifestation in adolescence and adulthood related to the under-managed emotional dysregulation in childhood is found to be associated with subtle confounding impact of 5-HTTLPR (serotonin-transporter-linked promoter region) genotype. The genotype of interest affects the neurochemistry, neurophysiology, and psychophysiology of the cognition for executive function. The established practice of using methylphenidate in treating ADHD surprisingly has a neurogenetic effect in targeting the genotype of interest. Methylphenidate provides neuroprotective effects throughout the neurodevelopment timeline from childhood to adulthood.</p><p><strong>Key messages: </strong>The emotional dysregulation element in ADHD which is often overlooked should be addressed to improve the prognostic outcomes in adolescence and adulthood.</p>","PeriodicalId":72654,"journal":{"name":"Complex psychiatry","volume":"9 1-4","pages":"70-88"},"PeriodicalIF":0.0,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035044","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":"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}
Complex psychiatryPub Date : 2023-02-03eCollection Date: 2023-01-01DOI: 10.1159/000529534
Yashika Bansal, Corey Fee, Keith A Misquitta, Sierra A Codeluppi, Etienne Sibille, Robert M Berman, Vladimir Coric, Gerard Sanacora, Mounira Banasr
{"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}
Complex psychiatryPub Date : 2023-02-03eCollection Date: 2023-01-01DOI: 10.1159/000529536
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
{"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}
Complex psychiatryPub Date : 2023-01-18eCollection Date: 2023-01-01DOI: 10.1159/000529164
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
{"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}