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.

References

• ¹
  Harris SE, Fox H, Wright AF, Hayward C, Starr JM, Whalley LJ, et al. The brain-derived neurotrophic factor Val66Met polymorphism is associated with age-related change in reasoning skills. Mol Psychiatry. 2006;11:505-13.
• ²
  Benjamin S, McQuoid DR, Potter GG, Payne ME, MacFall JR, Steffens DC, et al. The brain-derived neurotrophic factor Val66Met polymorphism, hippocampal volume, and cognitive function in geriatric depression. Am J Geriatr Psychiatry. 2010;18:323-31.
• ³
  Gong P, Zheng A, Chen D, Ge W, Lv C, Zhang K, et al. Effect of BDNF Val66Met polymorphism on digital working memory and spatial localization in a healthy Chinese Han population. J Mol Neurosci. 2009;38:250-6.
• ⁴
  Kennedy KM, Reese ED, Horn MM, Sizemore AN, Unni AK, Meerbrey ME, et al. BDNF val66met polymorphism affects aging of multiple types of memory. Brain Res. 2015;1612:104-17.
• ⁵
  Kambeitz JP, Bhattacharyya S, Kambeitz-Ilankovic LM, Valli I, Collier DA, McGuire P. Effect of BDNF val(66)met polymorphism on declarative memory and its neural substrate: a meta-analysis. Neurosci Biobehav Rev. 2012;36:2165-77.
• ⁶
  Chen SL, Lee SY, Chang YH, Wang TY, Chen SH, Chu CH, et al. The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese heroin-dependent patients. Sci Rep. 2015;5:8148.
• ⁷
  Chen SL, Lee SY, Chang YH, Chen SH, Chu CH, Wang TY, et al. The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese patients with bipolar disorder and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2014;51:99-104.
• ⁸
  Wang T. Does BDNF Val66Met polymorphism confer risk for posttraumatic stress disorder? Neuropsychobiology. 2015;71:149-53.
• ⁹
  Glaesmer H, Gunzelmann T, Braehler E, Forstmeier S, Maercker A. Traumatic experiences and post-traumatic stress disorder among elderly Germans: results of a representative population-based survey. Int Psychogeriatr. 2010;22:661-70.

Publication Dates

• Publication in this collection
  Sept 2017

History

• Received
  10 July 2017
• Accepted
  10 July 2017