The catechol-o-methyltransferase Val158Met polymorphism modulates organization of regional cerebral blood flow response to working memory in adults

Abstract

This study examined the effect of Catechol-O-Methyltransferase (COMT) Val158Met genotypes on the co-activation of brain areas involved in cognition during a working memory (WM) task. The pattern of concomitant region of interest (ROI) activation during WM performance varied by genotype: Val/Val showing the least and Met/Met the most covariance. There were no differences of performance on the WM task between the COMT genotypes. However, relatively better performance was associated with less concomitance of dorsolateral prefrontal cortex (DLPFC) and cingulate cortex for Val/Val, but more concomitance of DLPFC with AH for Met/Met. Within genotypes WM performance was significantly correlated with rCBF to the amygdala/hippocampus (AH) for Val/Val (r= 0.44, p=0.009), to the parietal lobe for Val/Met (r= 0.29, p=0.03), and to the thalamus for Met/Met (r= 0.32, p= 0.04). Different genotypes showed different regional specificity and concomitant activation patterns suggesting that varying dopamine availability induces different brain processing pathways to achieve similar WM performance.

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

“…Compared to the Met 158 homozygotes, COMT Val 158 and Val/Met 158 carriers were found to exhibit stronger sgACC rsFC associations with the left parahippocampus (PH), the ventromedial parts of the inferior frontal cortex, and the nucleus accumbens (NAc) and caudate nucleus. The involvement of hippocampal areas has been demonstrated earlier in different brain imaging studies examining the effect of the COMT Val 158 Met polymorphism on cognitive processes, usually reporting that Val 158 carriers perform worse on memory tasks than Met 158 homozygotes ( Bertolino et al, 2008 ; Heim et al, 2013 ); in particular in stressful situations ( Buckert et al, 2012 ). As mentioned before, Val 158 carriers recruited the parahippocampal regions while performing a house-matching task during emotional distraction, a typical attentional control related task ( Bishop et al, 2006 ).…”

Stress-related cellular pathophysiology as a crosstalk risk factor for neurocognitive and psychiatric disorders

“…Relatively better performance in working memory is associated with decreased coactivity between the dorsolateral PFC and ACC for Val/Val genotype, but increased coactivity between the dorsolateral PFC-amygdala/hippocampus for Met/Met genotype. This association correlates to the regional cerebral blood flow in the amygdala and hippocampus for Val/Val, the parietal lobe for Val/Met, and the thalamus for Met/Met [ 330 ].…”

Association between executive functions and COMT Val108/158Met polymorphism among healthy younger and older adults: A preliminary study

“…Some authors proposed that aging could magnify the Met allele advantage observed in younger adults [49][50][51]. On the other hand, other studies did not observe such a positive effect of carrying the Met allele in elderly [52][53][54][55] or even showed an advantage of carrying the Val allele [56][57][58]. However, the tasks administered vary in the involvement of executive processes, and one possible explanation to discrepancies observed is that not all executive processes are sensitive to COMT genetic polymorphism.…”