Gender effects of the COMT Val158Met genotype on verbal fluency in healthy adults

Abstract

Cognitive performance in healthy individuals is associated with gender differences in specific tests; a female advantage has been demonstrated in language tests, whereas a male advantage has been demonstrated in spatial relation examinations. The prefrontal cortex (PFC) mediates important cognitive domains and is influenced by dopamine (DA) activity. The single nucleotide polymorphism (SNP) rs4680 in the catechol‑O‑methyltransferase (COMT) gene results in an amino acid substitution from valine (Val) to methionine (Met). The Met allele has been demonstrated to decrease COMT enzyme activity and improve PFC cognitive function. COMT regulates DA activity in the PFC and exhibits gender effects. The aim of the present study was to investigate the gender‑specific effects of the COMT genotype on cognition in healthy young adults. Seventy‑six healthy subjects were genotyped for COMT rs4680 and submitted to an extensive range of neuropsychological tests assessing aspects of PFC function. The COMT Met allele influenced the performance of executive function. The results revealed gender effects of the COMT rs4680 Met allele on verbal fluency, with positive effects in males and negative effects in females. This suggested that DA activity affects cognitive function in different ways, according to gender.

Catechol-O-methyltransferase val158met Polymorphism Interacts with Sex to Affect Face Recognition Ability

“…The presence of an interaction between COMT val 158 met genotype and sex on face recognition is consistent with other studies that have found sex to affect the impact of the COMT polymorphism on cognitive phenotypes (e.g., O’Hara et al, 2006 ; Barnett et al, 2007 ; Soeiro-De-Souza et al, 2013 ; Gurvich and Rossell, 2015 ). O’Hara et al (2006) reported an interaction between COMT and sex on verbal memory, with male val homozygotes outperforming heterozygote and met homozygote men while females did not differ as a function of genotype.…”

“…Activity of the COMT enzyme is affected by variation in the gene coding for the COMT, which includes the COMT val 158 met polymorphism ( Chen et al, 2004 ). COMT activity is also regulated by oestrogen (e.g., Jiang et al, 2003 ), and certain effects of the COMT polymorphism on cognition appear to be sex-specific (e.g., Barnett et al, 2007 ; Soeiro-De-Souza et al, 2013 ; Gurvich and Rossell, 2015 ). This study investigated the potential sex-specific effects of the COMT val 158 met polymorphism on memory for faces in young adults.…”

“…Sex-specific effects of the COMT polymorphism on cognition could contribute to inconsistencies in the literature, as these effects may be obscured when sex is not considered in the analysis. There is accumulating evidence of COMT genotype-sex interactions on a range of phenotypes, including psychiatric disorders ( Harrison and Tunbridge, 2008 ), personality traits ( Chen et al, 2011 ), and forms of cognition such as verbal ability and memory ( O’Hara et al, 2006 ; Soeiro-De-Souza et al, 2013 ). Recently, COMT genotype was shown to interact with the α 2A -receptor gene promotor ( ADRA2A C-1291G) polymorphism and sex in affecting face perception ( Tamm et al, 2016 ).…”

Genetic markers of dopaminergic transmission predict performance for older males but not females

“…Additionally, although there are well-documented sex differences in DA transmission (Becker, 1990) and exploration of sex differences in public health research has been an NIH priority since the 1990s (Mazure and Jones, 2015), only a limited number of studies have tested for sex differences in associations between DA SNPs and behavior. Most of these studies had small sample sizes and conflicting results (Holtzer et al, 2010; Soeiro-De-Souza et al, 2013). The larger sample size here allows for a more conclusive investigation of whether males and females differ in how DA genotype may influence their performance.…”

Toward the Language Oscillogenome

“…Likewise, low voltage α has been associated with low activity levels in COMT, a catechol- O -methyltransferase that catalyzes the O -methylation of neurotransmitters like dopamine, epinephrine, and norepinephrine ( Enoch et al, 2003 ). COMT has been regularly associated with language performance and processing, and language acquisition, particularly with verbal fluency ( Krug et al, 2009 ; Soeiro-De-Souza et al, 2013 ; Sugiura et al, 2017 ), but also with reading abilities ( Landi et al, 2013 ). Finally, ZNF804A, a zinc finger binding protein, modulates hippocampal γ oscillations and thus the coordination of hippocampal and prefrontal distributed networks ( Cousijn et al, 2015 ).…”