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

Elzinga BM, Molendijk ML, Oude Voshaar RC, Bus BA, Prickaerts J, Spinhoven P, Penninx BJ - Psychopharmacology (Berl.) (2010)

Bottom Line: 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.Overall, BDNF Met carriers had reduced serum BDNF levels when exposed to CA in a dose-dependent way.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Health and Neuropsychology, Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands. elzinga@fsw.leidenuniv.nl

ABSTRACT

Rationale: 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.

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Related in: MedlinePlus

Mean values of serum levels of BDNF by exposure to Childhood Abuse (CA), recent stressful events, and BDNF Val66Met in the total group of life-time MDD-patients (n = 1,435)
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Fig1: Mean values of serum levels of BDNF by exposure to Childhood Abuse (CA), recent stressful events, and BDNF Val66Met in the total group of life-time MDD-patients (n = 1,435)

Mentions: Using a 2 (CA: yes/no) × 2 (recent stress: yes/no) × 2 (BDNF Val66Met: Val/Val vs. Met carriers) ANOVA on serum BDNF levels, we found no main effect of CA (P = .38) nor a main effect of Val66Met on BDNF levels (P = .33), but BDNF Val66Met moderated the effects of CA on serum BDNF levels (F1, 1,416 = 5.57, P = .018, see Fig. 1). Met carriers reporting CA had significantly lower levels of BDNF compared to Met carriers that did not report CA (F1, 506 = 4.19, P = .041, d = 0.19), whereas individuals reporting CA who were homozygous for the Val allele had similar levels of BDNF compared to homozygous Val carriers without CA (P = .12). Furthermore, in individuals reporting no CA, Met carriers had higher levels of BDNF compared to homozygous Val carriers (F1, 629 = 3.88, P = .049, d = 0.19), while in the CA group, Met carriers had similar levels of BDNF compared to homozygous Val carriers (P = .22). Exposure to recent stressful life events did not affect BDNF levels (P = .79). No other interaction effects were found (all Ps > .10).Fig. 1


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

Elzinga BM, Molendijk ML, Oude Voshaar RC, Bus BA, Prickaerts J, Spinhoven P, Penninx BJ - Psychopharmacology (Berl.) (2010)

Mean values of serum levels of BDNF by exposure to Childhood Abuse (CA), recent stressful events, and BDNF Val66Met in the total group of life-time MDD-patients (n = 1,435)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045516&req=5

Fig1: Mean values of serum levels of BDNF by exposure to Childhood Abuse (CA), recent stressful events, and BDNF Val66Met in the total group of life-time MDD-patients (n = 1,435)
Mentions: Using a 2 (CA: yes/no) × 2 (recent stress: yes/no) × 2 (BDNF Val66Met: Val/Val vs. Met carriers) ANOVA on serum BDNF levels, we found no main effect of CA (P = .38) nor a main effect of Val66Met on BDNF levels (P = .33), but BDNF Val66Met moderated the effects of CA on serum BDNF levels (F1, 1,416 = 5.57, P = .018, see Fig. 1). Met carriers reporting CA had significantly lower levels of BDNF compared to Met carriers that did not report CA (F1, 506 = 4.19, P = .041, d = 0.19), whereas individuals reporting CA who were homozygous for the Val allele had similar levels of BDNF compared to homozygous Val carriers without CA (P = .12). Furthermore, in individuals reporting no CA, Met carriers had higher levels of BDNF compared to homozygous Val carriers (F1, 629 = 3.88, P = .049, d = 0.19), while in the CA group, Met carriers had similar levels of BDNF compared to homozygous Val carriers (P = .22). Exposure to recent stressful life events did not affect BDNF levels (P = .79). No other interaction effects were found (all Ps > .10).Fig. 1

Bottom Line: 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.Overall, BDNF Met carriers had reduced serum BDNF levels when exposed to CA in a dose-dependent way.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Health and Neuropsychology, Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands. elzinga@fsw.leidenuniv.nl

ABSTRACT

Rationale: 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.

Show MeSH
Related in: MedlinePlus