The <b><i>COMT</i></b><b><i>p.Val158Met</i></b> Polymorphism and Cognitive Performance in Adult Development, Healthy Aging and Mild Cognitive Impairment

Abstract

Background: The impact of genetic polymorphisms on cognition is assumed to increase with age as losses of brain resources have to be compensated for. We investigate the relation of catechol-O-methyltransferase (COMT)p.Val158Met polymorphism and cognitive capacity in the course of adult development, healthy aging and the development of mild cognitive impairment (MCI) in two birth cohorts of subjects born between 1930 and 1932 or between 1950 and 1952. Methods: Thorough neuropsychological assessment was conducted in a total of 587 participants across three examination waves between 1993 and 2008. The COMT genotype was determined as a restriction fragment length polymorphism after PCR amplification and digestion with NlaIII. Results: Significant effects of the COMTp.Val158Met polymorphism were identified for attention and cognitive flexibility in the younger but not the older cohort. Conclusion: These results confirm the importance of the COMTp.Val158Met genotype on tasks assessing attention and cognitive flexibility in midlife but not in healthy aging and the development of MCI. Our findings suggest that the influence of COMT changes as a function of age, decreasing from midlife to aging.

Genetic association study of dyslexia and ADHD candidate genes in a Spanish cohort: Implications of comorbid samples

“…[ 74 ] between MAOA and executive attention and alerting, but the link between rs4680- COMT and the conflict index, based on ANT evaluation, shows that COMT is related to executive control. Several studies have recently associated variants of COMT with cognitive domains such as working memory [ 75 ] or cognitive flexibility [ 76 ]. In addition, this gene has previously been found to be associated with Stroop attentional tasks [ 77 ].…”

COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults

“…COMT has previously been associated with measures of cognition in cognitively normal older adults (Bellander et al, 2015; Starr et al, 2007), in particular episodic memory (Papenberg et al, 2014), working memory (Nagel et al, 2008), and attention (Degen et al, 2016). However, there have been a number of studies in cognitively normal older adults that have reported no significant associations with measures of episodic memory (O’Hara et al, 2006; Stuart et al, 2014), working memory (de Frias et al, 2010), verbal ability (O’Hara et al, 2006), attention or speed of processing (O’Hara et al, 2006).…”

“…Disruption to dopamine neurotransmission is associated with brain disease and mental illness. Consequently, allelic variation in the COMT gene has been associated with levels of cognition in cohorts of healthy individuals (Bellander et al, 2015; Degen et al, 2016; Diamond et al, 2004; Dumontheil et al, 2011; Egan et al, 2001; Goldberg et al, 2003; Malhotra et al, 2002; Nagel et al, 2008; Rosa et al, 2004, 2010; Sheldrick et al, 2008; Starr et al, 2007; Stefanis et al, 2005) and schizophrenia patients (Bilder et al, 2002; Egan et al, 2001; Goldberg et al, 2003; Nolan et al, 2004; Rosa et al, 2010), with carriage of COMT Val associated with poorer performance. However, several studies and a meta-analysis (Barnett et al, 2008) investigating healthy (Blanchard et al, 2011; de Frias et al, 2010; Ho et al, 2005; Liu et al, 2014; O’Hara et al, 2006; Papenberg et al, 2014; Potter et al, 2009; Stefanis et al, 2004; Stuart et al, 2014; Wardle et al, 2013) and diseased individuals (e.g., with schizophrenia (Dickerson et al, 2007; Ho et al, 2005; Zilles et al, 2012), depression (Opmeer et al, 2013; Potter et al, 2009; Wang et al, 2014), traumatic brain injury (Willmott et al, 2014), Parkinson’s disease (Hoogland et al, 2010), asymptomatic atherosclerosis (Bolton et al, 2010)) have reported no association between COMT genotype and cognitive performance.…”

“…However, several studies and a meta-analysis (Barnett et al, 2008) investigating healthy (Blanchard et al, 2011; de Frias et al, 2010; Ho et al, 2005; Liu et al, 2014; O’Hara et al, 2006; Papenberg et al, 2014; Potter et al, 2009; Stefanis et al, 2004; Stuart et al, 2014; Wardle et al, 2013) and diseased individuals (e.g., with schizophrenia (Dickerson et al, 2007; Ho et al, 2005; Zilles et al, 2012), depression (Opmeer et al, 2013; Potter et al, 2009; Wang et al, 2014), traumatic brain injury (Willmott et al, 2014), Parkinson’s disease (Hoogland et al, 2010), asymptomatic atherosclerosis (Bolton et al, 2010)) have reported no association between COMT genotype and cognitive performance. In particular, there is a general lack of consensus with respect to the impact that COMT genotype has on cognitive performance in healthy older adults, with studies finding a positive influence of COMT Met (Bellander et al, 2015; Degen et al, 2016; Nagel et al, 2008; Papenberg et al, 2014; Starr et al, 2007) or no significant effect (de Frias et al, 2010; O’Hara et al, 2006; Stuart et al, 2014). This inconsistency in results could, in part, be accounted for the by variability in cognitive decline due to underlying pathogenic changes occurring in the brain as a result of age related diseases.…”

Association of p.Val158Met COMT polymorphism with paranoid ideation in drug addicts

“…The Met allele has been associated with lower enzyme activity and elevated dopamine levels. Conversely, the Val allele has been associated with higher enzyme activity and reduced dopamine levels [15,16]. Therefore, COMT can modulate aspects of cognition, emotion and behavior [15,17].…”