The BDNF Val⁶⁶Met × 5‐HTTLPR × child adversity interaction and depressive symptoms: An attempt at replication

Abstract

Kaufman et al. [2006] reported a higher order interaction effect between specific genetic and environmental factors in a model of depressive symptoms, requiring independent replication. BDNF Val(66)Met and 5-HTTLPR genotypes were determined in female participants pertaining to a large ongoing twin study. Participants also filled in questionnaires on childhood adversity and depressive symptoms. Two- and three-way interactions between genetic polymorphisms and early adversity were examined in models of depressive symptoms. BDNF Met allele(s) moderated the effect of early adversity on depressive symptoms (two-way interaction), and this BDNF Met x childhood adversity interaction in turn was moderated by 5-HTTLPR genotype (three-way interaction). However, a main effect of BDNF Met on childhood adversity was also observed, possibly indicating confounding by gene-environment correlation. Higher order interaction effects involving BDNF Val(66)Met, 5-HTTLPR and childhood adversity may contribute to the etiology of depressive illness.

Resilience and mental health

“…This conclusion is in accordance with recent experimental and meta-analytic studies suggesting that some polymorphisms may not directly modulate vulnerability to depression, but may be components in the modulation of more general behaviour phenotypes via complex interactions of endoenvironments or endophenotypes (gene-gene interactions) with positive and negative exoenvironments (Feder et al, 2009;Kaufman et al, 2006;Uher & McGuffin, 2008;Wichers et al, 2008b). Moreover, the genome may be programmed by epigenetic mechanisms driven by interactions between an individual and their environment over their lifespan (Szyf, McGowan, & Meaney, 2007).…”

Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link

“…Determining the basis for this vulnerability is of key importance. Though nascent, the literature examining this topic suggests that early-life stress and BDNF genotype may interact to result in depression [120]. A recent study of 1,435 adults with a history of MDD reported that the experience of recent life stressors is associated with decreased levels of BDNF [121].…”

The implications of gene–environment interactions in depression: will cause inform cure?

“…A single nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF) has been shown to interact with the 5-HTTLPR on molecular and system level 18 and to further strengthen the G Â E between 5-HTTLPR and environmental adversity in epidemiological studies. 16,19,20 Specifically, human epidemiological studies indicate that BDNF 66met allele interacts with the 5-HTTLPR short allele to confer sensitivity to positive and negative environmental factors. This three-way interaction may be especially relevant to the treatment of depression as BDNF has been shown to mediate the effects of antidepressants, including those acting on the serotonin transporter.…”