The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met.
BACKGROUND
Recent 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 (Val(66)Met; RS6265), with the Met allele being associated with a decrease in activity-dependent secretion of BDNF compared to the Val allele.


METHODS
We 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 Val(66)Met polymorphism.


RESULTS
Overall, 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 Val(66)Met. 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.


CONCLUSIONS
These 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 Val(66)Met polymorphism in the face of stressful life events.
Elzinga
Bernet M
BM
Department of Clinical Health and Neuropsychology, Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands. elzinga@fsw.leidenuniv.nl
Molendijk
Marc L
ML
Oude Voshaar
Richard C
RC
Bus
Boudewijn A A
BA
Prickaerts
Jos
J
Spinhoven
Philip
P
Penninx
Brenda J W H
BJ
D000328:Adult; D054523:Adult Survivors of Child Abuse / Q000523:psychology*; D001008:Anxiety Disorders / Q000150:complications; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood* / Q000235:genetics; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000209:etiology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012189:Retrospective Studies; D013315:Stress, Psychological / Q000150:complications* / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor