Occupational burnout in healthcare workers from the perspective of a molecular genetic approach

The syndrome of professional burnout among medical workers, caused by exposure to non-industrial and a complex of harmful production factors and factors of the labor process (high tension, biological, chemical, physical factors), has acquired the character of an epidemic, threatening both the health of workers and the safety of patients. This syndrome is considered as prolonged occupational stress, which is realized in the disruption of adaptation to chronic exposure to high neuropsychiatric stress. The pathogenesis is based on functional overstrain of the nervous system, which is caused by psychoemotional stress in conditions of high intensity of the labor process (class 3.2–3.3). Traditional models that explain burnout solely by factors of the work environment cannot fully explain the individual variability of stress tolerance.

This review systematizes current data on the genetic and epigenetic determinants of variability within the framework of the biopsychosocial model and the concept of "differential susceptibility."

The results of the literature analysis demonstrate that the individual vulnerability profile to burnout is formed by polymorphisms in genes regulating key neurobiological systems: dopaminergic (COMT, DRD2, DRD4, SLC6A3 genes), serotonergic (SLC6A4, HTR1A, HTR2A), neuroplasticity (BDNF) and circadian rhythms (PER3). The authors paid special attention to the polymorphisms Val158Met of the COMT gene and Val66Met of the BDNF gene, which acted as markers of plasticity under chronic stress, mediating both vulnerability and resistance. Epigenetic mechanisms (DNA methylation of the SLC6A4, NR3C1, and DRD2 genes, changes in microRNA expression, and reactivation of endogenous retroviruses) are a dynamic link linking chronic occupational stress with molecular and cellular changes.

The analysis reveals the methodological limitations of existing studies, including the predominance of the "candidate genes" approach and the lack of studies performed using the genome-wide association search method. The prospects for overcoming the problem lie in the field of personalized occupational health: the use of genetic data to optimize work schedules, targeted prevention among risk groups, and the introduction of predictive biomonitoring based on epigenetic markers. For clinical validation, a transition to large-scale longitudinal studies is necessary.

Contributions:
Zaidullin I.I. — concept and design of the study, writing the text;
Valeeva E.T. — writing, editing;
Masyagutova L.M. — writing text, editing;
Gizatullina A.R. — collection and processing of material, statistical data processing.

Funding. The study had no funding.

Conflict of interest. The authors declare no conflict of interest.

Received: 05.05.2026 / Accepted: 15.05.2026 / Published: 27.06.2026

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