Sex Differences in the Effect of Brain-Derived Neurotrophic Factor (BDNF) Val66Met Polymorphism on Baseline EEG Connectivity

Abstract: Dependent on Val66Met polymorphism in brain-derived neurotrophic factor (BDNF) gene secretion of neurotrophin affects morphological and functional changes in the developing and mature nervous system, in particular, it may contribute to changes in connectivity associated with white matter degradation observed with aging. It was also shown that differences in connectivity between cortical structures associated with the Val66Met polymorphism are moderated by the sex of the subjects. However, there are no studies examining the effect of polymorphism on connectivity, taking into account age and gender differences. In this regard, the present study examined the associations of the Val66Met polymorphism of the BDNF gene with the characteristics of lagged phase synchronization based on EEG data in 223 younger (from 18 to 35 years old) and 134 older (over 55 years old) men and women. The analysis included connections between 84 cortical areas, identified on the basis of 42 Brodmann areas located in the left and right hemispheres. A statistically significant effect, including the factor of polymorphism, was the SEX × GENOTYPE interaction at the frequency of the α1 rhythm: in Val/Met men, the strength of 33 connections was higher compared to Val/Val. Strengthening of connections was observed mainly between the parahippocampal regions of different hemispheres. At the frequency of the γ rhythm, associated with the genotype differences in connectivity depended on gender and age. In young subjects, the scores of connectivity in Val/Val women were lower in comparison with men, however, no differences between Val/Val and Met-carriers were found in any age group. The combined effect of sex and BDNF genotype on the baseline EEG parameters of brain connectivity may be a background for further study of the role of these factors in the formation of basic characteristics of brain activity. © Pleiades Publishing, Inc. 2024. ISSN 0362-1197, Human Physiology, 2024, Vol. 50, No. 2, pp. 99–107. Pleiades Publishing, Inc., 2024.