The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met

Abstract

RationaleRecent findings show lowered brain-derived neurotrophic factor (BDNF) levels in major depressive disorder (MDD). Exposure to stressful life events may (partly) underlie these BDNF reductions, but little is known about the effects of early or recent life stress on BDNF levels. Moreover, the effects of stressful events on BDNF levels may in part be conditional upon a common variant on the BDNF gene (Val66Met; RS6265), with the Met allele being associated with a decrease in activity-dependent secretion of BDNF compared to the Val allele.MethodsWe investigated cross-sectionally in 1,435 individuals with lifetime MDD the impact of childhood abuse (CA) and recent life events on serum BDNF levels and assessed whether the impact of these events was moderated by the BDNF Val66Met polymorphism.ResultsOverall, BDNF Met carriers had reduced serum BDNF levels when exposed to CA in a dose-dependent way. Moreover, exposure to recent life events was also associated with decreases in BDNF levels, but this was independent of BDNF Val66Met. Moreover, when not exposed to CA, Met carriers had higher BDNF levels than the Val/Val individuals, who did not show decreases in BDNF associated with CA. Finally, these findings were only apparent in the MDD group without comorbid anxiety.ConclusionsThese gene–environment interactions on serum BDNF levels suggest that Met carriers are particularly sensitive to (early) stressful life events, which extends previous findings on the moderating role of the BDNF Val66Met polymorphism in the face of stressful life events.

BDNF Val66Met modifies the risk of childhood trauma on obsessive-compulsive disorder

“…The BDNF Val66Met polymorphism is functional, with the Met-allele resulting in reduced activity-dependent secretion of BDNF (Egan et al, 2003). Stress has been found to compound the effects that the BDNF Met-allele has on BDNF levels, resulting in increased anxiety and depression (Gatt et al, 2009;Elzinga et al, 2011). Indeed, Met-allele carriers have been found to be more sensitive to childhood abuse than Val-carriers, which could result in later psychopathology.…”

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

“…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]. This is consistent with research on murine models of early-life stress, in which a depressed phenotype in rats experiencing early maternal separation is associated with a decrease in mossy fibre development and neurogenesis in the hippocampi of these animals [111].…”

The risk for major depression conferred by childhood maltreatment is multiplied by BDNF and SERT genetic vulnerability: a replication study

“…1 Thus, maltreated children with the serotonin transporter (SERT) genotype conferring low levels of the SERT molecule (5-HTTLPR S allele carriers) seem to have an increased risk for depression compared to maltreated children with the 5-HTTLPR L/L genotype. 1,2 Similar 2-way (gene × environment) interactions between the BDNF Val66Met polymorphism and childhood maltreatment have also been described in the context of other mental health outcomes, [3][4][5] particularly depression. [6][7][8] Synergies between the serotonin (5HT) and BDNF systems have been suggested to contribute to the regulation of the develop ment and plasticity of neural circuits involved in the origin of affective disorders.…”