Problems of Radiation Medicine and Radiobiology

K. N. Loganovsky, M. O. Bomko, I. V.Abramenko, K. V. Kuts, N. I. Belous, S. V. Masiuk,
M. V. Gresko, T. K. Loganovska, K. Yu. Antypchuk, I. V. Perchuk, G. Yu. Kreinis, S. A. Chumak

State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine», 53 Melnykova str., Kyiv, 04050, Ukraine

NEUROPSYCHOBIOLOGICAL MECHANISMS OF AFFECTIVE AND COGNITIVE DISORDERS IN THE CHORNOBYL CLEAN-UP WORKERS TAKING INTO ACCOUNT THE SPECIFIC GENE POLYMORPHISMS

Relevance of the present work is determined by the considerable prevalence of both affective and cognitive disorders in the victims due to the Chornobyl accident, the pathogenesis of which is insufficiently studied.
Objective is to identify the neuropsychiobiological mechanisms of the formation of the remote affective and cognitive disorders following exposure to ionizing radiation taking into account the specific gene polymorphisms.
Design, object and methods of research. The retrospective and prospective cohort study with the external and internal control groups. The randomized sample of the male participants in liquidation of the consequences of the accident (Chornobyl clean-up workers, liquidators) at the Chornobyl nuclear power plant (ChNPP) in 1986–1987 (n = 198) recruited from the Clinico-epidemiological registry (CER) of NRCRM aged 39–87 (M ± SD: 60.0–8.5 years) with the external irradiation dose ranged 0.6–5900.0 mSv (M ± SD: 456.0 ± 760.0 mSv) was examined. The comparison group (n = 110) consisted of the unexposed patients of the Radiation Psychoneurology Department with the corresponding age and sex (the external control group). The internal control group included the liquidators irradiated at doses < 50.0 mSv (n = 42). The standard diagnostic neuropsychiatric scales, psychodiagnostic questionnaires and tests, neuropsychological methods (including the Wechsler Adult Intelligence Scale (WAIS) with premorbid IQ (pre-IQ) assessment), neuropsychiatric and psychophysiological methods (quantitative EEG (qEEG) and the auditory cognitive evoked potentials (Event-Related Potentials, ERP) were applied. The genotypes of the serotonin transporter gene SLC6A4 were determined by the 5_HTTLPR and rs25531 polymorphisms. The methods of descriptive and variation statistics, non-parametric criteria, regression-correlation analysis, survival analysis by Kaplan - Meier and risk analysis were used.
Results. Cerebrovascular diseases, organic mental and depressive disorders, mainly of radiation-stress-related nature, prevail among the liquidators. The overall risk of neuropsychiatric pathology increases (Pv < 0.001) with the irradiation dose. The verbal memory and learning are impaired, as well as the full IQ is reduced at the expense of the verbal one. The frequency of both mild cognitive impairment and dementia is risen. The cognitive impairment at doses > 0.3 Sv is dose-dependent (r = 0.4–0.7; p = 0.03–0.003). Affective disorders (depression) and neurocognitive deficit are more severe at higher doses of irradiation (≥ 50 mSv). In the left posterior temporal region (Wernicke’s area) the qEEG indices changes become dose-dependent at doses greater than 0.25–0.3 Sv. The disturbed brain information processes lateralized to the Wernicke's area are observed even at doses > 50 mSv. The carriers of intermediate and low-level genotypes (L_А/S, L_А/L_G, L_G/L_G, L_G/S, S/S) of the serotonin transporter gene SLC6A4 have more depressive disorders, especially severe ones, and tend to have more frequent and severe cognitive and stress-related disorders. The debut of depressive disorders in the carriers of the intermediate and low-activity genotypes occurs much earlier (Log-Rank Test = 4.43, p = 0.035) in comparison with the carriers of the high-performance genotype LА/ LА.
Conclusions. The radiation-induced dysfunction of the cortico-limbic system in the left dominant hemisphere of the human brain with a specific involvement of the hippocampus is considered to be the key cerebral basis of postradiation organic brain damage. The association of genotypes by 5_HTTLPR and rs25531 polymorphisms of the SLC6A4 gene with affective and cognitive disorders suggests the presence of neuropsychobiological features of these disorders associated with ionizing radiation depending on the certain gene polymorphisms.
Key words: Chornobyl disaster, ionizing radiation, cognitive disorders, affective disorders, gene polymorphisms.

Problems of radiation medicine and radiobiology.
2018;23:373_409. doi: 10.33145/2304-8336-2018-23-373-409.

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