Impact of genetic polymorphism on resting state functional connectivity in healthy subjects

Abstract

Brain-derived neurotrophic factor (BDNF) val66met polymorphism and catechol-O-methyltransferase (COMT) val158met polymorphism have been reported to affect neuropsychological function and brain structure. Functional imaging studies also revealed that these genetic polymorphisms have linked with activations of several brain regions during the task but there are only few studies about the impact of these genetic variations on the resting state functional connectivity. In this study, we hypothesized that there might be a difference in patterns of resting functional connectivity between BDNF and COMT genetic polymorphisms. To test these hypotheses, we used functional MRI (fMRI) to examine brain activity in a group of 23 healthy right-handed subjects (15 male/8 female; age: 24.13±3.67 years old). The Structured Clinical Interview for DSM-IV Non-patient Version was used to assess all participants to identify past and current psychiatric illnesses. The Korean version of the Wechsler Adult Intelligence Scale (K-WAIS) were also administered to all subjects (mean IQ: 112.96±9.99, mean years of education: 14.43 ±1.38 years). Whole blood was collected for genotyping and BDNF val66met and COMT val158met polymorphisms were detected by TaqMan allelic discrimination assays on ABI Prism 7500 Sequence Detection System. Functional imaging data were acquired using a 1.5-Tesla Avanto scanner while subjects kept their eyes closed during the scan. The posterior cingulate cortex (PCC) was selected as the seed region for the default mode network map and Statistical Parametric Mapping (SPM5) and REST package (REST version 1.3) were used to examine the functional connectivity of the PCC for each subject. According to the genotype, we divided subjects into two groups for each polymorphism: valallele homozygotes (n = 11)/met-allele carriers (n = 12) of BDNF val66met polymorphism and val-allele homozygotes (n = 8)/metallele carriers (n = 15) of COMT val158met polymorphism. A onesample t-test was performed for within-group analysis and a twosample t-test was used to examine the difference in the degree of functional connectivity between two groups.