COMT Val158Met genotypes differentially influence subgenual cingulate functional connectivity in healthy females

Abstract

Brain imaging studies have consistently shown subgenual Anterior Cingulate Cortical (sgACC) involvement in emotion processing. catechol-O-methyltransferase (COMT) Val158 and Met158 polymorphisms may influence such emotional brain processes in specific ways. Given that resting-state fMRI (rsfMRI) may increase our understanding on brain functioning, we integrated genetic and rsfMRI data and focused on sgACC functional connections. No studies have yet investigated the influence of the COMT Val158Met polymorphism (rs4680) on sgACC resting-state functional connectivity (rsFC) in healthy individuals. A homogeneous group of 61 Caucasian right-handed healthy female university students, all within the same age range, underwent rsfMRI. Compared to Met158 homozygotes, Val158 allele carriers displayed significantly stronger rsFC between the sgACC and the left parahippocampal gyrus, ventromedial parts of the inferior frontal gyrus (IFG), and the nucleus accumbens (NAc). On the other hand, compared to Val158 homozygotes, we found in Met158 allele carriers stronger sgACC rsFC with the medial frontal gyrus (MFG), more in particular the anterior parts of the medial orbitofrontal cortex. Although we did not use emotional or cognitive tasks, our sgACC rsFC results point to possible distinct differences in emotional and cognitive processes between Val158 and Met158 allele carriers. However, the exact nature of these directions remains to be determined.

The influence of COMT rs4680 on functional connectivity in healthy adults: A systematic review

“…Baeken et al. (2014) investigated a sample of 61 using a seed in the subgenual anterior cingulate cortex, chosen due to its role in emotion‐processing (Drevets, Savitz, & Trimble, 2008). Val carriers had significantly stronger functional connectivity between the subgenual anterior cingulate cortex and the left parahippocampal gyrus and the right inferior frontal gyrus.…”

“…Resting‐state connectivity analysis identified regions of the anterior cingulate cortex with increased connectivities associated with the Val allele, including the subgenual anterior cingulate cortex (Baeken et al., 2014) and dorsal anterior cingulate cortex (Gao et al., 2016), although Baeken et al. (2014) also reported an increased connectivity in Met carriers between the subgenual anterior cingulate cortex and the left medial frontal gyrus in their young‐adult female‐only sample. Task‐based findings showed some consistency; during successful memory retrieval, Met homozygotes had increased connectivity between medial temporal lobe and right anterior cingulate cortex (Dennis et al., 2010).…”

“…Favaro et al (2013) found no difference in connectivity between dorsolateral PFC, ventrolateral PFC and ventromedial PFC in young-adult females, although this is unsurprising if the effect of COMT rs4680 is only present in post-menopausal females and males as reported by Papaleo et al (2015). Whole brain analysis has also shown the right inferior frontal gyrus to have greater connectivity in Val homozygotes with seeds from the subgenual anterior cingulate cortex (Baeken et al, 2014) and orbitofrontal cortex (Gao et al, 2016).…”

“…Gender has shown an effect with COMT rs4680 (Elton et al., 2017), one study showing that COMT rs4680 influenced cognition in males but only in females post‐menopause (Papaleo et al., 2015). This review included two resting‐state studies with young‐adult female‐only samples, one of which found no effect of COMT rs4680 (Baeken et al., 2014), and one which found significant differences but was likely underpowered with three unequal groups totalling 30 (Favaro et al., 2013).…”

COMT Val158Met polymorphism influences the susceptibility to framing in decision‐making: OFC‐amygdala functional connectivity as a mediator

“…Moreover, accumulating evidence has implicated the role of COMT Val158Met polymorphism in modulating the resting-state network properties of the prefrontal cortex, which may in turn contribute to individual differences in a number of cognitive and affective processes, including working memory, executive functions, and emotion regulation (Baeken et al, 2014;Liu et al, 2010;Meyer et al, 2016;Tian et al, 2013;Tunbridge et al, 2013). In light of this, treating brain activity as an intermediate phenotype (Bigos and Weinberger, 2010), we hypothesized that the potential gene-behavior association may be mediated by the resting-state network properties of the prefrontal regions associated with the framing effect (e.g., dACC, vmPFC, and OFC) (De Martino et al, 2006;Roiser et al, 2009;Xu et al, 2013).…”