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

Abstract

Background Inflammation contributes to the development of depression in a subset of individuals, but risk factors that render certain individuals 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.

Potential unfavorable impacts of BDNF Val66Met polymorphisms on metabolic risks in average population in a longevous area

“…It is thus reasonable to assume that any BDNF polymorphism with lower BDNF activity may link to enhanced neuroinflammation and worsened cognitive outcome. This notion is underscored by the observation of Dooley and colleagues who noted a positive association between C-reactive protein levels and cognitive depressive symptoms among BDNF Met carriers of breast cancer survivors [50]. Therefore, we postulate that the control females who were enriched with BDNF Met allele in our study may also have higher inflammatory cytokines and poorer cognition, however this needs to be confirmed in our future longitudinal follow-up.…”

Depressive symptoms and neurotrophin levels in ostomy patients

“…In another study with 112 women post-treatment breast cancer survivors, the author evaluated depressive symptoms persist after the treatment completion and the Met allele of the BDNF Val66met polymorphism, suggesting these changes were activated via inflammatory processes arising from the treatment. Thus, BDNF Met allele could be a risk and vulnerability factor for inflammation-induced depression 38 . Suggesting an important role of inflammation in both depressive symptoms and changes in BDNF in this present study.…”

Novel rodent model of breast cancer survival with persistent anxiety-like behavior and inflammation

“…However, these disparate factors are difficult to differentiate in clinical populations and their likely mechanistic interactions remain either entangled or ignored. Among cancer survivors, enduring immune and inflammatory activation correlates with persistent negative affect (Dooley et al, 2016; Soygur et al, 2007, but see Bower et al, 2011; Orre et al, 2011), suggesting a possible immune mechanism. Indeed, mounting evidence indicates that mood comorbidities and inflammation exist prior to cancer treatments, and even prior to diagnosis (Sebti et al, 2015; Van Esch et al, 2012) in some cancer patients (Benoy et al, 2002; Lutgendorf et al, 2008; Michalaki et al, 2004; Wefel et al, 2015).…”