Val66Met BDNF polymorphism as a vulnerability factor for inflammation-associated depressive symptoms in women with breast cancer

Background: Inflammation contributes to the development of depression in a subset of individuals, but risk factors that render certain individuals particularly vulnerable to inflammation-associated depression are undetermined. Drawing from animal studies showing that reduced neuroplasticity mediates effects of inflammation on depression, we hypothesized that individuals genetically predisposed to lower levels of neuroplasticity would be more susceptible to inflammation-associated depression. The current study examined whether the Met allele of the BDNF Val66met polymorphism, which predisposes individuals to reduced levels of brain-derived neurotrophic factor (BDNF), a protein vital for neuroplasticity, moderates the association between inflammation and depressive symptoms.

Methods: Our sample was 112 women with early-stage breast cancer who had recently completed cancer treatment, which can activate inflammation. Participants provided blood for genotyping and assessment of circulating inflammatory markers, and completed a questionnaire assessing depressive symptoms, including somatic, affective, and cognitive dimensions.

Results: There was a significant interaction between C-reactive protein (CRP) and the BDNF Val66met polymorphism in predicting cognitive depressive symptoms (p=.004), such that higher CRP was related to more cognitive depressive symptoms among Met allele carriers, but not among Val/Val homozygotes. Post-hoc longitudinal analyses suggested that, for Met carriers, higher CRP at baseline predicted higher cognitive depressive symptoms across a one-year follow-up period (p<.001).

Conclusion: The BDNF Met allele may be a risk factor for inflammation-associated cognitive depressive symptoms among breast cancer survivors. Women with breast cancer who carry this genotype may benefit from early identification and treatment.

Limitation: BDNF genotype is an indirect measure of BDNF protein levels.