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

Abstract

Catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) genes have been found to interactively influence working memory (WM) as well as brain activation during WM tasks. However, whether the two genes have interactive effects on resting-state activities of the brain and whether these spontaneous activations correlate with WM are still unknown. This study included behavioral data from WM tasks and genetic data (COMT rs4680 and BDNF Val66Met) from 417 healthy Chinese adults and resting-state fMRI data from 298 of them. Significant interactive effects of BDNF and COMT were found for WM performance as well as for resting-state regional homogeneity (ReHo) in WM-related brain areas, including the left medial frontal gyrus (lMeFG), left superior frontal gyrus (lSFG), right superior and medial frontal gyrus (rSMFG), right medial orbitofrontal gyrus (rMOFG), right middle frontal gyrus (rMFG), precuneus, bilateral superior temporal gyrus, left superior occipital gyrus, right middle occipital gyrus, and right inferior parietal lobule. Simple effects analyses showed that compared to other genotypes, subjects with COMT-VV/BDNF-VV had higher WM and lower ReHo in all five frontal brain areas. The results supported the hypothesis that COMT and BDNF polymorphisms influence WM performance and spontaneous brain activity (i.e., ReHo).

Impact of brain‐derived neurotrophic factor genetic polymorphism on cognition: A systematic review

“…Sixty‐three studies were identified under the memory domain. The included studies had healthy controls ( n = 36) (Alfimova et al., ; Avgan et al., ; Beste, Schneider, Epplen, & Arning, ; Bombardier, Beauchemin, Gosselin, Poirier, & De Beaumont, ; Cathomas, Vogler, Euler‐Sigmund, de Quervain, & Papassotiropoulos, ; Canivet et al., ; Chen et al., , ; Dennis et al., ; De Beaumont et al., ; Erickson et al., ; Freundlieb et al., ; Gajewski et al., ; Gong et al., ; Gonzalez‐Giraldo et al., ; Gosselin et al., ; Huang et al., ; Jasinska et al., ; Karnik et al., ; Kennedy et al., ; Lim et al., ; Liu et al., ; Lamb et al., ; Miyajima et al., ; Montag et al., ; Raz et al., ; Richter‐Schmidinger et al., ; Schofield et al., ; Stuart, Summers, Valenzuela, & Vickers, ; Thow et al., ; Voineskos et al., ; Ward et al., , ; Wilkosc et al., ; Wegman, Tyborowska, Hoogman, Arias Vásquez, & Janzen, ; Yogeetha et al., ), dementia ( n = 1) (Kim et al., ), Alzheimer’s ( n = 3) (Gomar, Conejero‐Goldberg, Huey, Davies, & Goldberg, ; Lim et al., ; Lin et al., ), Parkinson’s ( n = 1) (Bialecka et al., ), cardiovascular disease ( n = 2) (Swardfager et al., ; Szabo et al., ), obsessive‐compulsive disease ( n = 1) (Tukel et al., ), multiple sclerosis ( n = 1) (Fera et al., ), psychosis ( n = 2) (Aas et al., ; Martinho et al., ), depression/anxiety disorders ( n = 2) (Molendijk et al., ; Strauss, Barr, & George, ), brain injury ( n = 2) (McAllister et al., ; Narayanan et al., ), amnestic mild cognitive impairment ( n = 1) (Yu et al., ), schizophrenia and bipolar disorders ( n = 9) (Cao et al., ; Egan et al.,…”

Working memory moderates the relation between the brain-derived neurotropic factor (BDNF) and psychotherapy outcome for depression

“…Also, both biological and psychological measures of learning processes at baseline should be included in future psychotherapy trials. As earlier studies pointed to an interaction between BDNF and COMT on working memory performance in healthy populations, it would be interesting for future studies to see whether the COMT plays a similar role in an psychotherapeutic setting (Chen et al, 2016;Nagel et al, 2008 Note. WMC = working memory capacity; Note that variables were coded as follows: gender, 1 = male, 2 = female; use of antidepressants, 0 = no, 1 = yes, fasting status, 0 = no (did eat), 1 = yes (did not eat), frequency condition, 0 = weekly, 1 = twice weekly.…”

“…Like BDNF, working memory capacity has shown to be lower in patients with MDD (Beevers, 2005;Snyder, 2013) and both have been related to early life stress (Goodman et al, 2019;Zhao et al, 2017). Multiple studies have supported the genetic and epigenetic link between BDNF and working memory capacity (Brooks et al, 2014;Chen et al, 2016;Wagner et al, 2018), memory performance (Azeredo et al, 2017) or attention (Mikoteit et al, 2015). In the study of Chen et al (2016), the relation between BDNF and working memory interacted with another gene that has repeatedly been linked to working memory: the Catechol-O-methyltransferase (COMT).…”

“…Multiple studies have supported the genetic and epigenetic link between BDNF and working memory capacity (Brooks et al, 2014;Chen et al, 2016;Wagner et al, 2018), memory performance (Azeredo et al, 2017) or attention (Mikoteit et al, 2015). In the study of Chen et al (2016), the relation between BDNF and working memory interacted with another gene that has repeatedly been linked to working memory: the Catechol-O-methyltransferase (COMT). Results showed that in individuals who were Val homozygote for BDNF, but not in BDNF Met-carriers, COMT Val homozygote was related to higher working memory capacity.…”

Effects of COMT rs4680 and BDNF rs6265 polymorphisms on brain degree centrality in Han Chinese adults who lost their only child

“…Both COMT rs4680 and BDNF rs6265 polymorphisms are suggested to moderate several neuroimaging structural phenotypes observed in PTSD 29,31,44 . In addition, recently, the interaction effect between COMT rs4680 and BDNF rs6265 on brain function has been reported in healthy subjects 45,46 . However, to the best of our knowledge, no study to date has investigated the effects of COMT rs4680, BDNF rs6265, or COMT by BDNF interaction on brain function in PTSD patients.…”