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RDoC and translational perspectives on the genetics of trauma-related psychiatric disorders.

ABSTRACT: Individuals with a history of child abuse are at high risk for depression, anxiety disorders, aggressive behavior, and substance use problems. The goal of this paper is to review studies of the genetics of these stress-related psychiatric disorders. An informative subset of studies that examined candidate gene by environment (GxE) predictors of these psychiatric problems in individuals maltreated as children is reviewed, together with extant genome wide association studies (GWAS). Emerging findings on epigenetic changes associated with adverse early experiences are also reviewed. Meta-analytic support and replicated findings are evident for several genetic risk factors; however, extant research suggests the effects are pleiotropic. Genetic factors are not associated with distinct psychiatric disorders, but rather diverse clinical phenotypes. Research also suggests adverse early life experiences are associated with changes in gene expression of multiple known candidate genes, genes involved in DNA transcription and translation, and genes necessary for brain circuitry development, with changes in gene expression reported in key brain structures implicated in the pathophysiology of psychiatric and substance use disorders. The finding of pleiotropy highlights the value of using the Research Domain Criteria (RDoC) framework in future studies of the genetics of stress-related psychiatric disorders, and not trying simply to link genes to multifaceted clinical syndromes, but to more limited phenotypes that map onto distinct neural circuits. Emerging work in the field of epigenetics also suggests that translational studies that integrate numerous unbiased genome-wide approaches will help to further unravel the genetics of stress-related psychiatric disorders.

SUBMITTER: Montalvo-Ortiz JL

PROVIDER: S-EPMC4754782 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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RDoC and translational perspectives on the genetics of trauma-related psychiatric disorders.

Montalvo-Ortiz Janitza L JL Gelernter Joel J Hudziak James J Kaufman Joan J

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20151122 1

Individuals with a history of child abuse are at high risk for depression, anxiety disorders, aggressive behavior, and substance use problems. The goal of this paper is to review studies of the genetics of these stress-related psychiatric disorders. An informative subset of studies that examined candidate gene by environment (GxE) predictors of these psychiatric problems in individuals maltreated as children is reviewed, together with extant genome wide association studies (GWAS). Emerging findi ...[more]

PMID: 26592203

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Project description:BackgroundNepal, like many other low-income countries, has a great burden of mental health issues but few resources to meet them. In addition, Nepal has endured several traumatic events in recent decades but the impact on mental health has not been studied in clinical settings. This study explores trauma-related psychiatric disorders and their correlates.Methods100 patients with a history of trauma who visited the outpatient psychiatry clinic at a University hospital in Kathmandu were assessed. The Composite International Diagnostic Interview 2.1 (CIDI) was used to evaluate lifetime and current depressive disorder, generalized anxiety disorder (GAD) and lifetime post-traumatic stress disorder (PTSD). Current PTSD was evaluated using PSTD Checklist-Civilian Version (PCL-C).ResultsThe median number of lifetime traumatic events was two. Natural disaster was the most common trauma type (84%) compared to other types of trauma. Rape was reported as the most traumatizing. Current PTSD was found in 15%, depression in 33% and GAD in 38% of the patients. The lifetime rates were PTSD 83%, depression 45% and GAD 40%. There was high comorbidity between the disorders. The 31 to 45 years age group, above high school education level and trauma types other than earthquake were independently associated with current PTSD. Marital status and upper socioeconomic status (SES) compared to upper-middle SES were independently associated with lifetime PTSD. Both lifetime and current depression rates were independently associated with the upper SES compared to upper-middle SES. Place of living, education above high school and lower-middle SES were significantly associated with lifetime and current GAD.ConclusionPTSD, depression and GAD were prevalent in a trauma exposed patient population visiting a psychiatric clinic in Nepal. High rates of comorbidities and several risk factors were identified. Our findings highlight the need for addressing trauma related disorders in clinical settings in developing countries.

Project description:ImportanceBeing exposed to trauma is a common childhood experience associated with symptoms and impairments in childhood.ObjectiveTo assess the association between cumulative childhood trauma exposure and adult psychiatric and functional outcomes.Design, setting, and participantsProspective, population-based cohort study of 1420 participants. A community representative sample of participants was assessed with structured Child and Adolescent Psychiatric Assessment interviews up to 8 times in childhood (ages 9-16 years; 6674 observations; 1993-2000) for lifetime trauma exposure as defined by the Diagnostic and Statistical Manual of Mental Disorders. Participants were followed up 4 times in adulthood (ages 19, 21, 25, and 30 years; 4556 observations of 1336 participants; 1999-2015) with the structured Young Adult Psychiatric Assessment Interview for psychiatric outcomes, functional outcomes, and evidence of a disrupted transition to adulthood. Analysis was completed in 2018.ExposureParticipants were assessed with the structured Child and Adolescent Psychiatric Assessment interview (parent and self-report) up to 8 times in childhood for lifetime trauma exposure (ages 9-16 years; 6674 observations; 1993-2000).Main outcomes and measuresParticipants were assessed up to 4 times with the structured Young Adult Psychiatric Assessment interview (self-report) in adulthood (ages 19, 21, 25, and 30 years; 4556 observations of 1336 participants; 1999-2015) for psychiatric outcomes, functional outcomes, and evidence of a disrupted transition to adulthood.ResultsAmong the 1420 study participants, 630 (49.0%) were female and 983 (89.4%) were white. By age 16 years, 30.9% of children (n = 451) were exposed to 1 traumatic event, 22.5% (n = 289) were exposed to 2 such events, and 14.8% (n = 267) were exposed to 3 or more. Cumulative childhood trauma exposure to age 16 years was associated with higher rates of adult psychiatric disorders (odds ratio for any disorder, 1.2; 95% CI, 1.0-1.4) and poorer functional outcomes, including key outcomes that indicate a significantly disrupted transition to adulthood (eg, failure to hold a job and social isolation). Childhood trauma exposure continued to be associated with higher rates of adult psychiatric and functional outcomes after adjusting for a broad range of childhood risk factors, including psychiatric functioning and family adversities and hardships (adjusted odds ratio for any disorder, 1.3; 95% CI, 1.0-1.5).Conclusions and relevanceCumulative childhood trauma exposure was associated with poor adult outcomes even after accounting for many of the childhood and family factors associated with both trauma exposure and poor adult outcomes. Childhood trauma exposures are common, but often preventable, thus providing a clear target for child-focused public health efforts to ameliorate long-term morbidity.

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RDoC and translational perspectives on the genetics of trauma-related psychiatric disorders.

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RDoC and translational perspectives on the genetics of trauma-related psychiatric disorders.

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