title: Genetic Moderation of Stress Effects on Corticolimbic Circuitry.
abstract: Stress exposure is associated with individual differences in corticolimbic structure and function that often mirror patterns observed in psychopathology. Gene x environment interaction research suggests that genetic variation moderates the impact of stress on risk for psychopathology. On the basis of these findings, imaging genetics, which attempts to link variability in DNA sequence and structure to neural phenotypes, has begun to incorporate measures of the environment. This research paradigm, known as imaging gene x environment interaction (iGxE), is beginning to contribute to our understanding of the neural mechanisms through which genetic variation and stress increase psychopathology risk. Although awaiting replication, evidence suggests that genetic variation within the canonical neuroendocrine stress hormone system, the hypothalamic-pituitary-adrenal axis, contributes to variability in stress-related corticolimbic structure and function, which, in turn, confers risk for psychopathology. For iGxE research to reach its full potential it will have to address many challenges, of which we discuss: (i) small effects, (ii) measuring the environment and neural phenotypes, (iii) the absence of detailed mechanisms, and (iv) incorporating development. By actively addressing these challenges, iGxE research is poised to help identify the neural mechanisms underlying genetic and environmental associations with psychopathology.
authors.affiliation: Department of Psychology, BRAIN Lab, Washington University in St Louis, St Louis, MO, USA.|Neurosciences Program, Division of Biology and Biomedical Sciences, Washington University in St Louis, St Louis, MO, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Bogdan
authors.affiliation: Neurosciences Program, Division of Biology and Biomedical Sciences, Washington University in St Louis, St Louis, MO, USA.
authors.forename: David
authors.identifier: http://orcid.org/0000-0002-1214-1965
authors.initials: D
authors.lastname: Pagliaccio
authors.affiliation: Department of Psychology, BRAIN Lab, Washington University in St Louis, St Louis, MO, USA.|Neurosciences Program, Division of Biology and Biomedical Sciences, Washington University in St Louis, St Louis, MO, USA.
authors.forename: David Aa
authors.initials: DA
authors.lastname: Baranger
authors.affiliation: Department of Psychology and Neuroscience, Laboratory of NeuroGenetics, Duke University, Durham, NC, USA.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Hariri
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D059647:Gene-Environment Interaction; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007206:Individuality; D008032:Limbic System / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism / Q000523:psychology