TY - JOUR
T1 - RDoC and translational perspectives on the genetics of trauma-related psychiatric disorders
AU - Montalvo-Ortiz, Janitza L.
AU - Gelernter, Joel
AU - Hudziak, James
AU - Kaufman, Joan
N1 - Funding Information:
This work was supported by the NIH R01MH098073 (JK, JH); the National Center for Posttraumatic Stress Disorder–Veterans Affairs Connecticut (JG, JK); and the VA Cooperative Study #575B, Genomics of Posttraumatic Stress Disorder in Veterans (JG, JK).
Funding Information:
This work was supported by the NIH R01MH098073 (JK, JH); the National Center for Posttraumatic Stress Disorder?Veterans Affairs Connecticut (JG, JK); and the VA Cooperative Study #575B, Genomics of Posttraumatic Stress Disorder in Veterans (JG, JK).
Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Child abuse
KW - Epigenetics
KW - Genetics
KW - Psychiatric disorders
KW - RDoC
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U2 - 10.1002/ajmg.b.32395
DO - 10.1002/ajmg.b.32395
M3 - Review article
C2 - 26592203
AN - SCOPUS:84954397418
SN - 1552-4841
VL - 171
SP - 81
EP - 91
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 1
ER -