“Evidence mounting for gene-by-environment interactions at the FKBP5 locus predicting psychiatric symptoms”, Thorhildur Haldorsdottir entitled her commentary in the December issue of Biological Psychiatry.
Haldorsdottir’s commentary was inspired by our recent study findings from the Helsinki Birth Cohort Study that were published in the same issue of Biological Psychiatry. In this article, Jari Lahti and colleagues exploited the circumstances that took place during World War II in Finland. These circumstances have given rise to a unique and objectively recorded early-life stress exposure: namely, early life stress that related to separation from biological parents in the childhood period and to temporary foster care (in families or institutions) abroad.
During World War II, nearly 80.000 Finnish children of varying ages and socioeconomic backgrounds were evacuated unaccompanied by their biological parents mainly to Sweden, but also to Denmark and Norway, to escape the strains of war.
Already some time ago, researchers in our DEPSY group went through the Finnish National Archives Registry. Of the 13.345 Helsinki Birth Cohort Study participants, 1.781 were identified to have been exposed to this type of early life stress at an average age of 5 years, for an average duration of 2 years. A series of our previous studies have demonstrated that as adults those exposed to this objectively recorded type of early life stress show a range of adverse health and other outcomes: increased risk of cardiometabolic and psychiatric disorders in later life, physiological feedback systems that are more attuned to psychosocial stress in midlife, and lower socioeconomic positions over the entire lifespan. Our further studies also show alterations in reproductive traits over the entire lifespan, and poorer neurocognitive functioning in early and late adulthood.
The new study by Lahti and colleagues demonstrate that FKBP5 polymorphisms (i.e., rs1360780, rs9470080, and rs9394309) and this objectively recorded early life stress interacted in predicting moderate to severe levels of depressive symptoms in midlife.
Depressive symptoms levels were consistently higher in those exposed to early life stress who carried one or two rare alleles of these three selected polymorphisms.
Haldorsdottir concludes in her commentary that “Despite the recent progress toward understanding this FKBP5-stress interaction, there are many questions that remain unanswered and ample room for future progress. Namely, further studies are needed to elucidate potential moderation effects of FKBP5 based on the type, timing, and duration of the environmental stressors and biological sex. A greater in-depth understanding of this interaction may ultimately translate into early detection of individuals at risk of developing a psychiatric disorder and guided preventative and treatment strategies to avoid the long-term negative effects of environmental stressors.” While our study moves beyond previous studies and provides further proof of the FKBP5-stress interaction, we couldn’t agree more with the Haldorsdottir’s conclusion.
/Katri Räikkönen