Interactions of BDNF Val66Met Polymorphism and Menstrual Pain on Brain Complexity

Intan Low; Po-Chih Kuo; Cheng-Lin Tsai; Yu-Hsiang Liu; Ming-Wei Lin; Hsiang-Tai Chao; Yong-Sheng Chen; Jen-Chuen Hsieh; Li-Fen Chen

doi:10.3389/fnins.2018.00826

Interactions of BDNF Val66Met Polymorphism and Menstrual Pain on Brain Complexity

Front Neurosci. 2018 Nov 20:12:826. doi: 10.3389/fnins.2018.00826. eCollection 2018.

Authors

Intan Low^{1

2}, Po-Chih Kuo³, Cheng-Lin Tsai⁴, Yu-Hsiang Liu¹, Ming-Wei Lin⁵, Hsiang-Tai Chao⁶, Yong-Sheng Chen^{7

8}, Jen-Chuen Hsieh^{1

2

9}, Li-Fen Chen^{1

2

4

9}

Affiliations

¹ Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
² Integrated Brain Research Unit, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
³ Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
⁴ Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
⁵ Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
⁶ Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁷ Department of Computer Science, National Chiao Tung University, Hsinchu, Taiwan.
⁸ Center for Emergent Functional Matter Science, National Chiao Tung University, Hsinchu, Taiwan.
⁹ Brain Research Center, National Yang-Ming University, Taipei, Taiwan.

Abstract

The irregularity and uncertainty of neurophysiologic signals across different time scales can be regarded as neural complexity, which is related to the adaptability of the nervous system and the information processing between neurons. We recently reported general loss of brain complexity, as measured by multiscale sample entropy (MSE), at pain-related regions in females with primary dysmenorrhea (PDM). However, it is unclear whether this loss of brain complexity is associated with inter-subject genetic variations. Brain-derived neurotrophic factor (BDNF) is a widely expressed neurotrophin in the brain and is crucial to neural plasticity. The BDNF Val66Met single-nucleotide polymorphism (SNP) is associated with mood, stress, and pain conditions. Therefore, we aimed to examine the interactions of BDNF Val66Met polymorphism and long-term menstrual pain experience on brain complexity. We genotyped BDNF Val66Met SNP in 80 PDM females (20 Val/Val, 31 Val/Met, 29 Met/Met) and 76 healthy female controls (25 Val/Val, 36 Val/Met, 15 Met/Met). MSE analysis was applied to neural source activity estimated from resting-state magnetoencephalography (MEG) signals during pain-free state. We found that brain complexity alterations were associated with the interactions of BDNF Val66Met polymorphism and menstrual pain experience. In healthy female controls, Met carriers (Val/Met and Met/Met) demonstrated lower brain complexity than Val/Val homozygotes in extensive brain regions, suggesting a possible protective role of Val/Val homozygosity in brain complexity. However, after experiencing long-term menstrual pain, the complexity differences between different genotypes in healthy controls were greatly diminished in PDM females, especially in the limbic system, including the hippocampus and amygdala. Our results suggest that pain experience preponderantly affects the effect of BDNF Val66Met polymorphism on brain complexity. The results of the present study also highlight the potential utilization of resting-state brain complexity for the development of new therapeutic strategies in patients with chronic pain.

Keywords: BDNF Val66Met polymorphism; brain complexity; chronic pain; magnetoencephalography; multiscale entropy; primary dysmenorrhea.