Interaction ofCOMTrs4680 andBDNFrs6265 polymorphisms on functional connectivity density of the left frontal eye field in healthy young adults

Abstract

As modulators of dopamine availability and release in the brain, COMT and BDNF polymorphisms have demonstrated interactions on human cognition; however, the underlying neural mechanisms remain largely unknown. In this study, we aimed to investigate the interactions of COMT rs4680 and BDNF rs6265 on global functional connectivity density (gFCD) of the brain in 265 healthy young subjects. We found a significant COMT × BDNF interaction on the gFCD in the left frontal eye field (FEF), showing an inverted U-shape modulation by the presumed dopamine signaling. This finding was consistently repeated in the gFCD analyses using other four connection thresholds. Our findings reveal a COMT × BDNF interaction on the FCD in the left FEF, which may be helpful for understanding the neural mechanisms of the COMT × BDNF interactions on the FEF-related cognitive functions. Hum Brain Mapp 37:2468-2478, 2016. © 2016 Wiley Periodicals, Inc.

Interaction Effects of BDNF and COMT Genes on Resting-State Brain Activity and Working Memory

“…Mapping onto Li et al (2016) findings, we found consistent U-shaped associations between presumed dopamine level and ReHo of five regions in the frontal lobe. These associations were statistically significant in terms of both interactions and post-hoc contrasts.…”

“…Most relevant to our work, Li et al's (2016) found that COMT-M + /BDNF-M + and COMT-VV/BDNF-VV groups showed higher global functional connectivity density than the other two groups ( COMT-VV/BDNF-M + and COMT-M + /BDNF-VV ). These results have been explained by interactive effects of BDNF and COMT on dopamine levels.…”

“…Indeed, previous research has reported mixed findings, with some studies linking the Val allele to better performance on learning (Soliman et al, 2010), episodic memory (Egan et al, 2003), and WM tasks (Echeverria et al, 2005; Rybakowski et al, 2006), whereas others showed conflicting findings (Hansell et al, 2007; Schofield et al, 2009). Some of these conflicting results may well have been due to potential interactions between BDNF and COMT as found in our study on WM and ReHo, as well as in previous studies on paired-associates learning, stimulation-induced cortical plasticity (Witte et al, 2012), gray matter volumes (Mortby et al, 2014), and functional connectivity (Wang et al, 2015; Li et al's, 2016). …”

“…In contrast, the other two combinations ( COMT- VV and BDNF- VV; COMT- M+ and BDNF- M+) are expected to show moderate levels of dopamine. Li et al (2016) finding that the latter two groups (with presumed medium levels of dopamine signaling) showed higher global functional connectivity density than the other two groups (either low or high levels of dopamine signaling) fits the commonly accepted inverted U-shaped association between dopamine level and outcomes (see Wang et al, 2015; Li et al's, 2016 for detailed discussions).…”

“…Considering the smaller sample size with imaging data, we followed previous research (Li et al's, 2016) and combined M/V with M/M to form the Met-carrier group. Subjects were divided into four groups, ordered from high to low in presumed dopamine signaling (see Li et al's, 2016): COMT -M+/ BDNF -VV, COMT -M+/ BDNF -M+, COMT -VV/ BDNF -VV, and COMT -VV/ BDNF -M+. The design matrix was specified with four regressors defined as “1” (subject in the group) or “0” (subject not in the group).…”