BDNF Val66Met polymorphism and memory performance in older adults: the Met carrier effect is more complex than previously thought: Authors' reply.

Genetic association studies have presented inconsistent findings regarding the effects of the functional BDNF Val66Met polymorphism and cognitive function in healthy subjects and psychiatric patients, with heterogeneity in effect sizes across studies.1-4 As these candidate gene studies have employed relatively small samples, it is difficult to interpret discrepant findings, which are the norm in genetic association research. By aggregating data across studies, meta-analyses provide a systematic method of evaluating such discrepant findings, as regarding the association between BDNF Val66Met polymorphism and memory function. In this context, a recently published meta-analysis estimated the effect of the BDNF Val66Met polymorphism on declarative memory tasks in 5,922 subjects, as well as on hippocampal grey matter volume in 2,985 subjects and on task-related change in hippocampal response measured by functional magnetic resonance imaging (fMRI) in 362 subjects.5 The authors of this meta-analysis found evidence that declarative memory performance, hippocampal volume, and hippocampal activation are all reduced in BDNF Met allele carriers in comparison to Val/Val homozygotes. In our study, we examined the effect of the BDNF Val66Met polymorphism on declarative memory performance in a sample of 87 older adults recruited by convenience among community-based elders in Porto Alegre, Brazil. Our analysis yielded further evidence on the genetic contribution of the BDNF Val66Met polymorphism in memory performance, demonstrating that BDNF Met allele carriers had lower delayed verbal recall and a decline in memory retention as compared to Val/Val homozygotes. Although our findings provided additional evidence of an association between the BDNF Val66Met polymorphism and memory, we have no such evidence regarding peripheral levels of BDNF. In fact, the BDNF Val66Met SNP does not affect plasma BDNF levels, as pointed out in recent research.6,7 Therefore, unlike Drs. Lipov and Candido, we do not consider the lack of peripheral BNDF measurement a limitation of our study. Nevertheless, we agree that, to better understand the dynamics of the BDNF changes demonstrated in our study, novel approaches to measurement of levels of the corresponding proteins are necessary.

Although candidate gene studies have linked the BDNF Val66Met polymorphism with posttraumatic stress disorder (PTSD), a recent meta-analysis did not find a significant overall effect of this SNP on susceptibility to PTSD.8 On the other hand, subgroup analyses suggested that the stress status of the control group could affect the relationship between the BDNF Val66Met polymorphism and PTSD risk. Considering the heterogeneity of findings associating this polymorphism with cognitive performance in elderly adults, our study was designed to investigate the effects of this genetic variant on declarative memory performance specifically in this population. Considering that the percentage of older adults with PTSD is around 3%,9 the overall impact of this diagnosis in our sample is probably negligible.

Disclosure

The authors report no conflicts of interest.