The 'Warrior' COMT Val/Met Genotype Occurs in Greater Frequencies in Mixed Martial Arts Fighters Relative to Controls.

Author:Tartar, Jaime L.
 
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Introduction

Dopamine signaling in the prefrontal cortex has been shown to moderate aggression levels. In particular, dopamine signaling in the mesocorticolimbic system is involved in multiple facets of aggressive behaviors including the initiation, execution, and conclusion of aggressive acts (Ferrari et al., 2003; Haney et al., 1990; Mos, 1979; Van Erp and Miczek, 2000). Indeed, dopamine antagonists represent the most widely used pharmacological treatment in efforts to curb aggressive behavior in humans (McDougle et al., 1998). Dopamine has been shown to be a critical factor in individual differences in competitive ability and is associated with competitive behavior in males across many species. For example, zebra finches with higher tyrosine hydroxylase mRNA and higher D1 receptor (D1-R) mRNA show advantages in competitive ability (Eswine et al., 2019) In rats, learned aggression is associated with low D2 receptor densities (Suzuki et al., 2010). Increased activity of D2 receptors in the hypothalamus region increases aggressive defensive behavior in cats (Sweidan et al., 1991).

Catechol-O-methyltransferase (COMT) is one of two major enzymes responsible for catecholamine catabolism. The COMT gene is well expressed across the brain and regulates dopamine signaling in the prefrontal cortex. COMT variants can be used as molecular genetic markers associated with anxiety, pain, and stress responsivity. A functional single nucleotide polymorphism (SNP) in the COMT gene (rs4680) leads to an amino acid substitution of methionine (Met) in place of valine (Val) at position 158 (Val158Met). The Val158Met polymorphism is associated with decreased activity of the COMT enzyme in the prefrontal cortex and amygdala, increasing risk for early-onset major depression, panic disorders, and anxiety in adolescents and adults (Qiu et al., 2015). The COMT allele status has also been shown to functionally alter DA activity in the PFC wherein COMT Met (low-activity; high dopamine) allele carriers outperform Val (high-activity; low dopamine) allele carriers on a variety of cognitive tasks (Bruder et al., 2005; Diaz-Asper et al., 2008; Egan et al., 2001; Goldberg et al., 2003). Interestingly, the relationship between genotype and cognitive performance appears to reverse under stressful conditions. Stress increases PFC DA levels, and Met allele carriers (with higher DA) show performance deficits relative to Val allele carriers. This pattern reflects the inverted U-shaped function of DA activity where too little (Val allele) or too much (Met allele carriers under stress) DA is associated with poor cognitive performance (Goldman-Rakic et al., 2000).

Given the abundance of research that associates aggressive behavior with increased dopamine activity, combined with the COMT warrior/worrier model (GoldmanRakic et al., 2000), we predicted that GG homozygote "warriors" would be more prevalent in fight sport athletes. In line with the warrior/worrier theory, increased physical and psychological stress during a match would push this genotype into a high dopamine level state. Whereas A allele carriers, who have high dopamine levels at baseline, would be pushed into the far right side of the inverted U- a level for suboptimal cognitive functioning. Given that our previous research showed a relationship between COMT genotypes and biomarkers of stress (Hill et al., 2018; Serrano et al., 2019), we also assessed these measures and their possible relationship to genotype status.

Methods

Participants

Participant descriptors by group can be seen in Table 1: Eighty-three male participants (MMA = 21, athlete = 21, non-athlete = 41) were tested in the current study (M age = 23.39 years, SD = 4.56). Self-reported ethnicities were as follows: White/Caucasian = 49, Black/African American = 17, Asian = 9, Multiracial = 9. A power calculation was not conducted since we aimed to test the maximum number of (relatively rare) participants we could recruit in the MMA group. All of the MMA athletes competed professionally under a variety of organizations including The Ultimate Fighting Championship, One Championship, and Bellator. Due to sample quality or technical error we were unable to genotype 2 participants and analyze sAA on one participant. To control for circadian fluctuations in cortisol secretion, participants were tested between 2:00-5:00 pm, when cortisol secretion, while not at the circadian nadir, is at a low, declining value (Bailey and Heitkemper, 2001). The Nova Southeastern University Institutional Review Board approved this study and written consent was acquired from all subjects before participating in the study procedure. Following consent, the height (M height =176.58 cm, SD = 21.68) and weight (M weight =81.09 kg, SD = 13.23) of participants were measured. 1 mL of saliva was collected into two 1.5 mL polyethylene centrifuge tubes using a passive salivation technique using a small sterile cylinder in order to measure selected biomarkers, outlined below. Saliva was immediately stored at -20[degrees]C.

Biomarkers

Cortisol and Alpha Amylase. Saliva samples were run in duplicate and quantified via a human cortisol enzyme immunoassay (EIA) kit and a sAA Kinetic Enzyme Assay Kit per the manufacturer's instructions (Salimetrics LLC, USA). The samples were immediately read on a BioTek ELx800 plate reader (BioTek Instruments, Inc., USA) at 450 nm with a correction at 630 nm. All samples were within the detection ranges indicated in the immunoassay kits, and the variations of sample readings were...

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