COMT rs4680 G-allele Carriers in Police and Military SOF have Less Interference Tendency and Better Reaction Time

Alain Dössegger

Introduction

Gene polymorphism rs4680 in catechol-O-methyltransferase (COMT) is a prominent modifier of the dopaminergic signaling pathway that modifies stress resilience and memory [4]. The resulting Met-(A-allele) and Val-(G-allele) protein variants are associated with a detrimental or favorable response in executive function [1]. In stressful situations, G-allele carriers typically demonstrate a “warrior” phenotype that is characterized by a better processing of aversive stimuli [7], better-aiming control [3], and a higher pain threshold [6], but also increased susceptibility to PTSD [2] than the “worrier” phenotype of non-G-allele carriers. In close-quarters battle (CQB) or other urban warfare situations, a warrior strategy might be advantageous. The ability to react under stress, the speed of information processing, and the ability to inhibit overlearned answers to simple tasks, i.e., no freeze or to pull a trigger, is critical for Special Operation Forces (SOF). We believe that G-allele carriers show better performance under stress.

Method

Within the scope of the P(O|TS) study, 144 SOF operators and SOF candidates agreed to genotyping determined by high resolution analysis of the melting curve (HRM) of the amplicons from salvia samples. Reaction speed was measured with the complex multiple-stimuli reaction determination test (DT) and interference tendency under stress with the STROOP test using the Vienna Test System (Schuhfried, Austria). We measured reaction time with a practical reaction test adapted for SOF, using Fitlight® and Simunition®/FX handgun. COMT G-allele carriers and non-carriers (i.e., AA genotypes) were compared using Bayesian independent samples T-Test [6] with an uninformed Cauchy prior distribution and an informed Normal prior distribution (0.5, .05), accounting for our prior belief.

Results

DT reaction time and STROOP write interference showed moderate and very strong evidence for the alternative hypothesis relative to the null hypothesis, with G-allele carriers having better reaction time and less interference tendency. The average reaction time in the Fitlight/FX first test attempt was lower in G-allele carriers, although statistically anecdotal (Bayes factor < 3). The effect vanishes with the second attempt. Details are shown in table 1.

Table 1: Test results

Discussion

Reduced inteference tendency and reactive stress tolerance characterize people with peak stress performance [5]. SOF COMT G-allele carriers showed better performance under stress, confirming our prior belief derived from the literature. Mechanisms involve a four-fold reduction in COMT activity, the increasing dopamine levels inhibiting stress-induced rises in blood flow to the brain’s prefrontal cortex in A-allele carriers. Within a CQB mimicking test setting with a handgun, the effect is no longer visible, especially after some familiarization, possibly due to training that overrides genotype effects. Key message: SOF operators with COMT Val-(G)-allele may act better under stress compared to AA genotypes. The awareness of such genetic differences could be used to tailor cognitive training to improve the ability to act under stress (e.g., meditation, nutritional interventions) for operators and SOF candidates and to compose teams according to individual strengths.

References

1. Barnett JH et al.: Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls. Molecular Psychiatry 2007; 12(5): 502-509. mehr lesen
2. Kolassa IT et al.: The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-o-methyltransferase Val(158)Met polymorphism. Biol Psychiatry 2010; 67(4): 304-308. mehr lesen
3. Lage GM et al.: Association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and manual aiming control in healthy subjects. PLoS One 2014; 9(6): e99698. mehr lesen
4. Malhotra AK et al.: A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. Am J Psychiatry 2002; 159(4): 652-654. mehr lesen
5. Rouder JN et al.: Bayesian t tests for accepting and rejecting the null hypothesis. Psychonomic Bulletin & Review 2009; 16(2): 225-237. mehr lesen
6. Schuhfried G: STROOP Inference Test Manual, S. GmbH, Editor. 2023: Mödling, Austria.
7. Smolka MN et al.: Gene–gene effects on central processing of aversive stimuli. Molecular Psychiatry 2007; 12(3): 307-317. mehr lesen
8. Vetterlein A, Monzel M, Reuter M: Are catechol-O-methyltransferase gene polymorphisms genetic markers for pain sensitivity after all? - A review and meta-analysis. Neurosci Biobehav Rev 2023; 148: 105112. mehr lesen

Author

Alain Dössegger
Swiss Federal Institute of Sport, Magglingen/Schweiz
Hochschulhauptgebäude HHG 316
2532 Magglingen Switzerland
E-Mail: alain.doessegger@baspo.admin.ch