The interplay of variations in the FKBP5 gene and adverse life events in predicting the first onset of depression during a ten-year follow-up

Aims: The co-chaperone FKBP5 of hsp-90 is an important modulator of glucocorticoid receptor function. Associations between SNPs in the FKBP5 gene and a faster antidepressant treatment response and an increased recurrence of depressive episodes were shown by us previously. Since stressful life events also contribute to depression via effects on HPA axis, FKBP5 could be involved in gene-environment processes. Aim: To explore interaction and correlation effects between variations in the FKBP5 gene and adverse events in predicting the first onset of a major depressive episode (MDE) in a ten-years prospective-longitudinal community survey. Methods: Analyses are based on 884 caucasians without baseline MDE who participated during the whole study period. Data were assessed with the M-CIDI according to DSM-IV. Five SNPs within the FKBP5 gene were selected for genotyping. Results: Whereas no genetic main effects were observed, the effect of trauma on incident MDE was clearly evident only among subjects homozygous for the minor alleles, but not among subjects with the other genotypes. There was an interaction between the five SNPs and traumatic (but not separation) events with the strongest effect for severe trauma (min pcorrected<0.0000001). Variants in the five FKBP5 SNPs were not associated with any adverse event category. Conclusions: These hypothesis-generating results support a potential gene-trauma interaction for the first onset of depression.