期刊
HUMAN BRAIN MAPPING
卷 37, 期 4, 页码 1602-1613出版社
WILEY
DOI: 10.1002/hbm.23123
关键词
major depression disorder; stress-related disorders; childhood abuse; general population; FKBP5 gene; gene-environment interaction; CTQ; MRI; SPM8; VBM8
资金
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Siemens Healthcare, Erlangen, Germany
- Federal State of Mecklenburg-West Pomerania
- German Research Foundation [DFG: GR 1912/5-1]
- German Federal Ministry of Education and Research (BMBF) [01ZX1314E]
ObjectiveThe FKBP5 gene codes for a co-chaperone that regulates glucocorticoid receptor sensitivity and thereby impacts the reactivity of the hypothalamic-pituitary-adrenal (HPA)-axis. Evidence suggested that subjects exposed to childhood abuse and carrying the TT genotype of the FKBP5 gene single nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to stress-related disorders. MethodThe hypothesis that abused TT genotype carriers show changes in gray matter (GM) volumes in affect-processing brain areas was investigated. About 1,826 Caucasian subjects (age65 years) from the general population [Study of Health in Pomerania (SHIP)] in Germany were investigated. The interaction between rs1360780 and child abuse (Childhood Trauma Questionnaire) and its effect on GM were analyzed. ResultsVoxel-based whole-brain interaction analysis revealed three large clusters (FWE-corrected) of reduced GM volumes comprising the bilateral insula, the superior and middle temporal gyrus, the bilateral hippocampus, the right amygdala, and the bilateral anterior cingulate cortex in abused TT carriers. These results were not confounded by major depressive disorders. In region of interest analyses, highly significant volume reductions in the right hippocampus/parahippocampus, the bilateral anterior and middle cingulate cortex, the insula, and the amygdala were confirmed in abused TT carriers compared with abused CT/CC carriers. ConclusionThe results supported the hypothesis that the FKBP5 rs1360780 TT genotype predisposes subjects who have experienced childhood abuse to widespread structural brain changes in the subcortical and cortical emotion-processing brain areas. Those brain changes might contribute to an increased vulnerability of stress-related disorders in TT genotype carriers. Hum Brain Mapp 37:1602-1613, 2016. (c) 2016 Wiley Periodicals, Inc.
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