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; p<0.05). In explorative analyses, the most severe degree of sexual and emotional abuse also yielded significant interaction effects (p<0.05). This study revealed interactions between physical abuse and rs1360780 of the FKBP5 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.
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Acknowledgements
SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (Grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (Grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. The University of Greifswald is a member of the ‘Center of Knowledge Interchange’ program of the Siemens AG. This work was also funded by the German Research Foundation (DFG: GR 1912/5-1). HJG, KA, and CS had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. We thank Daniela Becker, Varinia Popek, Elena Stoll, Frauke Grieme, Matthias Becker, Daniela Schrader, Julia Schwanda, Daniel Grams, and Andrea Rieck for their contribution to the study (organization, data collection, and data management).
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External financial support in the past 5 years: Hans Joergen Grabe: German Research Foundation; Federal Ministry of Education and Research Germany; speakers honoraria from Bristol-Myers Squibb, Eli Lilly, Novartis, Eisai, Wyeth, Pfizer, Boehringer Ingelheim, Servier; and travel funds from Janssen-Cilag, Eli Lilly, Novartis, AstraZeneca, and SALUS-Institute for Trend-Research and Therapy Evaluation in Mental Health. Carsten Spitzer: Travel funds and speakers honoraria from Janssen-Cilag and Boehringer Ingelheim; research grant from the ‘Stiftung zur Aufarbeitung der SED-Diktatur.’ Christian Schwahn, Katja Appel, Jessie Mahler, Andrea Schulz, Kristin Fenske, Jan Stender, Alexander Teumer: none. Sven Barnow: German Research Foundation; Federal Ministry of Health Germany. Ulrich John: German Research Foundation; German Cancer Aid; European Union; Federal Ministry of Education and Research Germany; Federal Ministry of Health; Social Ministry of the Federal State of Mecklenburg-West Pomerania of Germany. Matthias Nauck: research grants from the Federal Ministry of Education and Research Germany, Bio-Rad Laboratories GmbH, Siemens AG, Zeitschrift für Laboratoriumsmedizin, Bruker Daltronics, Abbott, Jurilab Kuopio, Roche Diagnostics, Dade Behring, DPC Biermann, and Becton Dickinson. Henry Völzke: research grants by Sanofi-Aventis, Biotronik, the Humboldt Foundation, the Federal Ministry of Education and Research (Germany), and the German Research Foundation. Reiner Biffar: research grants by Federal Ministry of Education and Research Germany, Ivoclar, Sirona, Dentsply, Kavo, Wieland Ceramics, GC, Heraeus, Dentaurum, Merz-Dental, the Krupp-Foundation, German Society of Dentistry (DGZMK), German Society of Prosthetic Dentistry and Dental Materials (DGZPW). Harald J Freyberger: German Research Foundation; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Family Ministry of the Federal Republic of Germany; speakers honoraria from AstraZeneca, Lilly, Novartis, and travel funds from Janssen-Cilag.
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Appel, K., Schwahn, C., Mahler, J. et al. Moderation of Adult Depression by a Polymorphism in the FKBP5 Gene and Childhood Physical Abuse in the General Population. Neuropsychopharmacol 36, 1982–1991 (2011). https://doi.org/10.1038/npp.2011.81
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DOI: https://doi.org/10.1038/npp.2011.81
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