INTRODUCTION:

High-intensity sports activities are associated with substantial physical and psychological demands, necessitating continual adaptation by athletes^1,2. Recent meta-analyses (2019–2022) emphasize that well-designed strategies for preventing and detecting stress-related disorders at an early stage significantly affect both athletic performance and career longevity^3-7.

Psychological factors-in particular, the level of anxiety and motivation—directly influence competitive success and increase the risk of injuries when training intensity escalates^8-11.

One of the key mechanisms of adaptation in sports is the functioning of the autonomic nervous system (ANS), which balances sympathetic and parasympathetic influences under growing training and competitive stress^12-16. Individual differences in heart rate regulation are largely determined by genetic factors, including genes responsible for catecholamine metabolism. Heart rate variability (HRV) is increasingly regarded as an objective marker of ANS status and its response to psychophysiological stress^4,9,17,18. Monitoring HRV in athletes facilitates the timely detection of overtraining and allows for optimizing training programs to minimize the risk of performance deterioration^13,14,16,19.

Of particular interest is the gene encoding catechol-O-methyltransferase (COMT), which exhibits a functional polymorphism, Val158Met (rs4680), affecting enzyme activity and thus dopamine and adrenaline levels in the central nervous system^3,6,12,21. Several studies have noted that carriers of the Val/Val variant may demonstrate higher stress resilience, correlating with better athletic performance^1,7,12. Conversely, Met/Met (AA) is often associated with elevated emotional reactivity^5,9,14,15, although findings among different researchers are contradictory, especially regarding anxiety and sports burnout syndrome^4,13,19. Investigating the role of COMT Val158Met in shaping autonomic and psychoemotional responses is therefore highly relevant, as it enables more precise prediction of exhaustion risk and the development of personalized preventive and recovery strategies^6,10,17,21.

Accordingly, a comprehensive analysis of the impact of the COMT Val158Met polymorphism on HRV indicators, anxiety levels, subjective stress, and burnout risk is needed to refine individualized training programs and preserve athletic longevity^{11,13,14,16,20}. Based on current literature, the GG (Val/Val) genotype is hypothesized to promote parasympathetic predominance (increased SDNN, RMSSD, etc.) and lower emotional exhaustion, whereas the AA (Met/Met) genotype may be linked to greater sympathetic activity and heightened anxiety^6,12,14,21.

The aim of the present study is to conduct a comparative analysis of HRV parameters, psychoemotional status, and susceptibility to sports burnout among athletes with different COMT Val158Met genotypes. Evaluating the contribution of this polymorphism to adaptation under high physical and psychological loads will provide a rationale for personalized approaches to training and recovery measures for the prevention of sports burnout^1,3,6,10,20.

MATERIALS AND METHODS:

This study was conducted in the format of a single-stage comparative analysis. All procedures were approved by the Local Ethics Committee of the Specialized Sports School for Team Sports and Track and Field under the Department of Sports of Samarkand Region (Pr.№23 dated December 23, 2022), and were in compliance with the principles of the Declaration of Helsinki (2013 revision). Each participant provided written informed consent, which included details of the research objectives, scope, and potential risks.

A total of 100 male athletes (49 soccer players and 51 track-and-field athletes) aged 17–20 years, each having practiced their respective sports for at least one year on a regular basis, were enrolled in the study. The sample size of 100 was determined based on analogous research findings [Smith A.L., 2020; Volkov V.A., 2021], where the combination of molecular-genetic analysis and heart rate variability (HRV) assessment in groups of 80–120 individuals achieved a statistical power of at least 80% at a significance level of α = 0.05. An additional rationale for including exactly 100 participants was the availability of athletes in this age category at specialized schools during the data collection period.

Inclusion criteria:

Age 17–20 years; regular training sessions (at least three times per week) for one year or more; no medical contraindications for physical activity; no chronic cardiovascular, neurological, or endocrine disorders.

Exclusion criteria:

Injuries or conditions preventing full participation in the testing protocol; use of medications that may affect anxiety or stress levels (antidepressants, sedatives, etc.); refusal to participate in the study or provision of incomplete/unconfirmed informed consent.

Genotype determination (COMT Val158Met): Venous blood samples were collected in the morning (8:00–10:00) after an overnight fast in EDTA vacuum tubes. DNA was extracted using the “DNA-Express-Blood” kit (Litekh, Russia), followed by polymerase chain reaction (PCR) with the “SNP-Express-RV” kit (Litekh, Russia) on a DT Prime thermal cycler (DNA-Technology, Russia). Three genotype variants were identified: AA (Met/Met), AG (Val/Met), and GG (Val/Val).

Assessment of anxiety, stress, and sports burnout was carried out using the Zung Self-Rating Anxiety Scale (Zung SAS, 20 items), the Perceived Stress Scale (PSS-10), and the Athlete Burnout Questionnaire (ABQ), which includes subscales for emotional exhaustion, depersonalization, and reduced sense of accomplishment. All surveys were administered in the morning on non-competition days, approximately one hour after waking (before training) to minimize the influence of accumulated fatigue. Participants were advised to get adequate sleep (7–8 hours) and to refrain from stimulants (caffeine, energy drinks) for at least 12 hours before testing. Questionnaires were completed in a separate room without bystanders to ensure confidentiality and a neutral environment. In case of incorrect or missing answers, participants were allowed to clarify or supplement information during an individual interview.

Heart rate variability (HRV) assessment was performed using the computer-based “Biomouse” system (NeuroLab, Russia). Measurements were taken either seated or supine in a calm environment at 20–24°C, at least two hours after the last meal and not less than 24 hours following intensive training. Data were processed using the “Varicard-2.51” software. The following parameters were analyzed: Time-domain indices: SDNN (standard deviation of NN intervals), RMSSD (root mean square of successive differences), pNN50 (percentage of NN intervals differing by more than 50 ms); Frequency-domain indices: LF, HF, and the LF/HF ratio; Derived indices: stress index (IS), variation range (VR), and the index of autonomic balance (IAB)

Statistical processing: Data are presented as the mean± standard error of the mean (M ± m). The Kolmogorov–Smirnov test was used to assess the normality of distribution. For normally distributed data, between-group comparisons (AA, AG, GG) were performed using the Student’s t-test (unpaired). If normality could not be assumed, the Mann–Whitney U-test was applied. The Fisher’s exact test was used to compare percentages. The significance threshold for all analyses was set at p<0.05. The Bonferroni correction was applied for multiple comparisons. Statistical calculations were performed using the SPSS Statistics 11.0 software package (IBM).

RESULTS:

A total of 100 athletes (49 soccer players and 51 track and field athletes) were analyzed in this study. They were classified by COMT Val158Met genotype as follows: AA (Met/Met) – 40 individuals, AG (Val/Met) – 43 individuals, and GG (Val/Val) – 17 individuals. The main heart rate variability (HRV) and psychoemotional status parameters are presented in Table 1.

Table 1. Key Physiological and Psychoemotional Parameters in Athletes with Different COMT Val158Met Genotypes

Parameter	Reference Normative Values (Literature Data)	AA (Met/ Met) (n = 40)	AG (Val/ Met) (n = 43)	GG (Val/Val) (n = 17)
Heart Rate (HR), bpm	60–72	74 ± 2,1	71 ± 2,7*	69 ± 3,1*
SDNN (ms)	80–120	83 ± 10	95 ± 9*	107 ± 11*
RMSSD (ms)	30–50	26 ± 4,2	33 ± 5,3*	40 ± 5.0*
pNN50 (%)	10–25	12 ± 2,3	18 ± 3,1*	24 ± 3.7*
Variation Range (VR), ms	250–350	220 ± 40	270 ± 35*	330 ± 50*
Tension Index (IS), a.u.	100–200	340 ± 50	250 ± 45*	180 ± 35*
Autonomic Balance Index (IAB), a.u.	200–300	360 ± 40	280 ± 35*	220 ± 30*
Zung Anxiety Scale, points	25–45	52 ± 3.5	45 ± 3.1*	35 ± 3.,2*
Perceived Stress Scale (PSS-10), points	10–20	25 ± 2.7	20 ± 2.4*	15 ± 2.1*
Emotional Exhaustion (ABQ), points	8–12	14,5 ± 2.8	10,2 ± 2.5*	8,6 ± 2.2*

Notes: Emotional exhaustion is one of the subscales of the Athlete Burnout Questionnaire (ABQ).

Data are presented as M ±m (mean±standard error of the mean). HRV Indices: SDNN: Standard deviation of NN intervals; RMSSD: Root mean square of successive differences; pNN50: Percentage of NN intervals that differ by more than 50ms; VR (Variation Range): The difference between the maximum and minimum NN interval; IS (Tension Index): Higher values indicate increased sympathetic tone; IAB (Autonomic Balance Index): Higher values suggest a shift toward sympathetic dominance. Higher SDNN, RMSSD, pNN50, and VR values indicate a predominance of the parasympathetic component and a broader range of regulatory capacity. Lower IS and IAB values reflect reduced sympathetic influence and better autonomic balance. Zung Anxiety Scale scores: <45 = Low anxiety; 45–59 = Moderate anxiety; ≥60 = High anxiety. Perceived Stress Scale (PSS-10) scores: 0–13 = Low stress; 14–26 = Moderate stress; 27–40 = High stress. *p< 0.05 compared with the AA (Met/Met) group; a Bonferroni correction was applied for multiple comparisons.

As shown in Table 1, the highest resting heart rate (HR) was observed in AA carriers (74±2.1bpm), whereas in the AG group it decreased to 71±2.7bpm (p<0.05 vs. AA). The lowest HR values were recorded in GG carriers (69±3.1bpm), which is 6.8% lower than in the AA group (p<0.05). Time-domain HRV parameters demonstrated that the mean SDNN in the AA group was 83±10ms; in the AG group, it increased to 95 ± 9 ms (p<0.05), and reached 107±11 ms in the GG group (p<0.05 vs. AA). Hence, the SDNN of GG carriers was 28.9% higher compared to AA, suggesting better overall heart rate variability and more flexible adaptation to load. Among AA participants, the RMSSD was 26±4.2 ms, significantly lower (p<0.05) than in AG (33±5.3 ms). The highest RMSSD values (40±5.0 ms, p<0.05) were observed in the GG group, indicating a dominant parasympathetic component in heart rate regulation.

The proportion of NN intervals differing by more than 50 ms (pNN50) was 12±2.3% in AA, 18±3.1% in AG (p<0.05), and 24±3.7% in GG (p<0.05). The difference between AA and GG exceeded 50%, reflecting a marked predominance of parasympathetic influences in Val/Val carriers. Variation range (VR) was the lowest in the AA group (220±40ms), increased to 270±35ms in AG (p<0.05), and reached 330±50ms in GG (p<0.05). The highest index of autonomic balance (IAB) was recorded in AA (360±40 arbitrary units), while in AG (280±35) and GG (220±30) it was significantly lower (p<0.05), indicating reduced sympathetic influence and more balanced autonomic regulation in AG and GG carriers. Among AA athletes, the stress index (IS) amounted to 340±50 arbitrary units, significantly higher than in AG (250±45, p<0.05) and GG (180±35, p<0.05). A comparison between AG and GG also revealed a 28% reduction in IS in the GG group (p<0.05). The elevated IS in AA points to pronounced sympathetic tone and increased stress potential.

According to the Zung Self-Rating Anxiety Scale, the AA group scored 52±3.5 on average, representing the upper boundary of moderate anxiety. The AG group’s score decreased to 45±3.1 (p<0.05), while the lowest score (35±3.2, p<0.05) was observed in GG, indicative of low anxiety. The highest Perceived Stress Scale (PSS-10) value (25±2.7) was found in AA, compared to 20± 2.4 in AG (p<0.05) and 15±2.1 in GG (p<0.05), yielding a difference of over 40% between AA and GG and suggesting a lower subjective stress load in GG carriers. Emotional exhaustion was greatest in the AA group (14.5±2.8 points), moderate in the AG group (10.2±2.5, p<0.05), and lowest in GG (8.6±2.2, p<0.05). The difference of approximately 41% between AA and GG statistically confirms the reduced tendency of Val/Val carriers toward burnout syndrome.

DISCUSSION:

COMT Val158Met is a functional polymorphism that affects the rate of catecholamine metabolism (dopamine, norepinephrine, and epinephrine). The Val (G) allele is associated with higher enzymatic activity, leading to more rapid dopamine catabolism and therefore relatively low dopaminergic stimulation in the prefrontal cortex (PFC). It is believed that this contributes to improved tolerance of physical and psychological stressors (a higher “stress threshold”). In contrast, the Met (A) allele confers lower COMT enzymatic activity and slower dopamine metabolism, thereby increasing its concentration in the synaptic cleft. While this may enhance cognitive functions (e.g., memory, learning capacity) under moderate loads, it can also provoke heightened emotional and stress reactivity under high-intensity stressors. From the perspective of cardiac autonomic regulation, dopamine and related catecholamines (epinephrine, norepinephrine) influence the balance between the sympathetic and parasympathetic nervous system. Athletes with high COMT activity (Val/Val) generally exhibit better tolerance for high-volume and high-intensity training, while maintaining more pronounced parasympathetic input into heart rate regulation (as reflected by elevated SDNN, RMSSD, and pNN50 values). Conversely, low enzymatic activity (Met/Met) leads to increased excitability and sympathetic dominance, manifested in higher heart rate, elevated stress indices (IS, IAB), and lower HRV values.

The results obtained confirm the significant role of the COMT Val158Met polymorphism in regulating both heart rate and psycho-emotional parameters in athletes. Specifically, the AA (Met/Met) genotype was associated with higher heart rate and lower variability measures (SDNN, RMSSD, pNN50), as well as elevated levels of anxiety and stress. By contrast, the GG (Val/Val) genotype demonstrated a predominance of parasympathetic tone and reduced susceptibility to emotional exhaustion. Our findings are consistent with those of He et al. (2016), who reported that Val/Val athletes exhibit greater resilience to training stress. However, unlike the study by Thompson et al. (2021), which found no differences between Met/Met and Val/Val in anxiety levels, we observed a statistically significant increase in anxiety and stress indices (p<0.05) among AA (Met/Met) carriers. This discrepancy may stem from differences in study design (sample size, type of sport) and participant age. Moreover, a more in-depth assessment of types of higher nervous activity (HNA) revealed additional genotype distribution patterns, an aspect rarely addressed in previous investigations (Danilov et al., 2020).

Our study underscores the practical value of identifying an individual’s COMT Val158Met genotype when planning training regimens and providing psychological support. For AA carriers, stress management techniques (relaxation methods, cognitive-behavioral programs) and a more conservative recovery regimen may be warranted to reduce the risk of overtraining. Meanwhile, athletes in the GG group may tolerate high training loads with fewer signs of emotional exhaustion, although motivational oversight is still required, as heightened physiological resilience does not preclude mental overload. Therefore, these findings provide a basis for personalized strategies aimed at preventing burnout syndrome and maintaining an optimal balance between training load and recovery.

Study limitations

Sample and geographical scope: All participants were from a single region and represented only two sports disciplines (soccer and track and field), which may limit the generalizability (extrapolation) of the findings to athletes of other sports or from different regions.

Gender factor: Only male athletes were included in this study, making it impossible to assess the effect of COMT Val158Met in female populations. Future research involving female athletes could provide valuable insights into gender-specific influences.

Lack of longitudinal observations: This study was cross-sectional; to evaluate the dynamics of HRV and psycho-emotional status over seasonal or multi-year time frames, a long-term prospective follow-up would be necessary.

Consideration of additional genetic factors: We focused primarily on COMT Val158Met, although other genes (e.g., ACE, ACTN3, BDNF) may also contribute to stress resilience and athletic performance.

Addressing these limitations in future research will enable a more comprehensive understanding of the genetically determined mechanisms that underpin adaptation to training and competitive stress. Nevertheless, the present findings already underscore the importance of incorporating genotypic differences when designing individualized training programs, which may enhance both the efficiency and safety of the athletic process.

Theoretical significance:

The results obtained deepen the understanding of genetically driven adaptation mechanisms in response to sports-related stress. This study broadens current knowledge of how the COMT Val158Met polymorphism impacts not only physiological parameters (HRV) but also psycho-emotional indicators (anxiety, burnout).

Practical recommendations:

Coaches and sports physicians should consider athletes’ genotypic characteristics when planning training intensity and volume. AA carriers may require additional recovery measures (relaxation, psychological support), whereas GG carriers can generally tolerate higher loads while maintaining optimal motivation and a lower risk of stress reactions. Sports psychologists should give special attention to AA carriers due to their heightened emotional reactivity and, if necessary, adapt interventions to manage anxiety and prevent burnout. Employing individualized recovery programs based on HRV data and genetic testing can improve the efficiency of the training cycle and reduce the likelihood of overtraining.

Future research directions:

Conducting longitudinal studies to track changes in HRV parameters and psycho-emotional status across different stages of the competitive season.

Investigating the influence of other genetic factors (e.g., ACE, BDNF) alongside COMT Val158Met to more accurately identify genetic profiles requiring tailored training approaches.

Including female athletes in future samples to assess gender-related aspects of the influence of COMT polymorphism on autonomic and psycho-emotional regulation.

CONCLUSION:

Overall, the findings indicate that the GG (Val/Val) genotype of COMT Val158Met is associated with a more pronounced parasympathetic regulation of cardiac activity (higher SDNN, RMSSD, pNN50) and lower levels of anxiety and stress, suggestive of greater stress resilience and robust recovery capacity. Conversely, AA (Met/Met) carriers exhibit increased heart rate, lower HRV measures, and higher anxiety and emotional exhaustion scores, reflecting a propensity toward sympathetic overactivity and burnout risk. The AG (Val/Met) genotype occupies an intermediate position, displaying a moderately balanced autonomic profile and an average level of psycho-emotional strain. These results confirm that accounting for COMT Val158Met genotype and HRV parameters can enhance the efficiency and safety of athletic training, providing a basis for personalized training and recovery programs.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 31.03.2025 Revised on 17.07.2025

Accepted on 14.10.2025 Published on 16.03.2026

Available online from March 18, 2026

Research J. Pharmacy and Technology. 2026;19(3):1151-1156.

DOI: 10.52711/0974-360X.2026.00164

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