Moderation of Adult Depression by a Polymorphism in the FKBP5 Gene and Childhood Physical Abuse in the General Population
Open Access
- 8 June 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Neuropsychopharmacology
- Vol. 36 (10), 1982-1991
- https://doi.org/10.1038/npp.2011.81
Abstract
Childhood maltreatment and depressive disorders have both been associated with a dysregulation of the hypothalamic–pituitary–adrenal axis. The FKBP5 gene codes for a co-chaperone regulating the glucocorticoid-receptor sensitivity. Previous evidence suggests that subjects carrying the TT genotype of the FKBP5 gene single-nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to adverse effects of experimental stress. We therefore tested the hypothesis of an interaction of childhood abuse with rs1360780 in predicting adult depression. In all, 2157 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and Childhood Trauma Questionnaire. The DSM-IV diagnosis of major depressive disorder (MDD) was assessed by interview. Genotypes of rs1360780 were taken from the Affymetrix Human SNP Array 6.0. Significant interaction (p=0.006) of physical abuse with the TT genotype of rs1360780 was found increasing the BDI-II score to 17.4 (95% confidence interval (CI)=12.0–22.9) compared with 10.0 (8.2–11.7) in exposed CC/CT carriers. Likewise, the adjusted odds ratio for MDD in exposed TT carriers was 8.2 (95% CI=1.9–35.0) compared with 1.3 (0.8–2.3) in exposed subjects with CC/CT genotypes. Relative excess risk due to interaction (RERI) analyses confirmed a significant additive interaction effect (RERI=6.8; 95% CI=0.64–33.7; ppFKBP5 gene, confirming its role in the individual susceptibility to depression. Given the large effect sizes, rs1360780 could be included into prediction models for depression in individuals exposed to childhood abuse.Keywords
This publication has 36 references indexed in Scilit:
- Interaction of FKBP5 with Childhood Adversity on Risk for Post-Traumatic Stress DisorderNeuropsychopharmacology, 2010
- Cohort Profile: The Study of Health in PomeraniaInternational Journal of Epidemiology, 2010
- Interaction of FKBP5, a Stress-Related Gene, with Childhood Trauma Increases the Risk for Attempting SuicideNeuropsychopharmacology, 2010
- Modern EpidemiologyAnnals of Emergency Medicine, 2008
- The FKBP5-Gene in Depression and Treatment Response—an Association Study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) CohortBiological Psychiatry, 2008
- Association of FKBP5 Polymorphisms and Childhood Abuse With Risk of Posttraumatic Stress Disorder Symptoms in AdultsJama-Journal Of The American Medical Association, 2008
- Influence of Child Abuse on Adult DepressionArchives of General Psychiatry, 2008
- Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatmentNature Genetics, 2004
- Study of Health in Pomerania (SHIP): A health examination survey in an east German region: Objectives and designInternational Journal of Public Health, 2001
- The Corticosteroid Receptor Hypothesis of DepressionNeuropsychopharmacology, 2000