A translational approach to the genetics of anxiety disorders.

Autor: McGregor NW; Systems Genetics Working Group, Department of Genetics, Stellenbosch University, South Africa; SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, South Africa. Electronic address: nwm@sun.ac.za., Dimatelis JJ; Department of Human Biology, University of Cape Town, South Africa., Van Zyl PJ; Department of Human Biology, University of Cape Town, South Africa., Hemmings SMJ; Division of Molecular Biology and Human Genetics, Stellenbosch University, South Africa., Kinnear C; SAMRC Center for Tuberculosis Research, South Africa., Russell VA; Department of Human Biology, University of Cape Town, South Africa., Stein DJ; SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, South Africa., Lochner C; SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, South Africa.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2018 Apr 02; Vol. 341, pp. 91-97. Date of Electronic Publication: 2017 Dec 27.
DOI: 10.1016/j.bbr.2017.12.030
Abstrakt: There have been important advances in our understanding of the genetic architecture of anxiety disorders. At the same time, relatively few genes have reached genome wide significance in anxiety disorders, and there is relatively little work on how exposure to an adverse environment impacts on gene expression in either animal models or human clinical populations. Here we assessed differential expression of genes of the dorsal striatum involved in synaptic transmission in an animal models of early adversity (maternal separation followed by restraint stress), and investigated whether variants in these genes were associated with risk for anxiety disorders, particularly in the presence of environmental stressors. Fifty-two male Sprague Dawley rats underwent maternal separation, and gene expression was studied using array technology. The human homologues of the differentially expressed genes were screened and analysed in a DSM-IV anxiety disorders cohort, and healthy controls (patients, n = 92; controls, n = 194), using blood. Two candidate genes (Mmp9 and Bdnf) were aberrantly expressed in the experimental rodent group relative to controls. Four single nucleotide polymorphisms (SNPs) in the human homologues of these genes were significantly associated with susceptibility for anxiety disorders (MMP9: rs3918242 and BDNF: rs6265, rs10835210 and rs11030107). Three of these (BDNF: rs6265, rs10835210, rs11030107) were found to interact significantly with childhood trauma severity resulting in increased likelihood of an anxiety disorder diagnosis. This study provides insights into the utility of rat models for identifying molecular candidates for anxiety disorders in humans.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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