Associations Between Self-Reported and Objectively Recorded Early Life Stress, FKBP5 Polymorphisms, and Depressive Symptoms in Midlife

Abstract

Background: FK506-binding protein 51 is involved in hypothalamic-pituitary-adrenal axis regulation. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene have been shown to interact with retrospectively self-reported early life stress (ELS) in patients with psychiatric disorders. We examined interactions between three selected FKBP5 SNPs and self-reported and objectively recorded ELS in relation to depressive symptoms in midlife.

Methods: This study comprised 1431 Helsinki Birth Cohort Study participants genotyped for FKBP5 SNPs shown to alter cortisol metabolism (rs1360780, rs9470080, and rs9394309). Participants completed the Beck Depression Inventory (BDI) at ages 61.5 years (time 1) and 63.4 years (time 2); 165 and 181 participants were separated from their parents in childhood as a result of evacuations during World War II as indicated by self-reports and the Finnish National Archives registry, respectively.

Results: Associations between self-reported and objectively recorded ELS, but not stressful events in midlife, and the mean BDI score (average of time 1 and time 2) or mild to severe BDI scores (10-63 points at time 1 and time 2), or both, were moderated by the FKBP5 variants (p values for interactions < .05; p values between self-reported and objectively recorded ELS in these interactions > .18). Mean BDI scores or odds for having mild to severe BDI scores, or both, increased according to number of minor alleles and haplotypes derived from these alleles in the separated groups, but not in the nonseparated groups.

Conclusions: FKBP5 variations in combination with self-reported and objectively recorded ELS predict more pronounced depressive symptoms in midlife. Our findings confirm previous retrospective findings in a prospective epidemiologic study setting.

Keywords: Cortisol; Depression; Early life stress; FKBP5; HPA; Longitudinal study; Separation.