NEUROPSYCHOBIOLOGICAL MECHANISMS OF AFFECTIVE AND COGNITIVE DISORDERS IN THE CHORNOBYL CLEAN-UP WORKERS TAKING INTO ACCOUNT THE SPECIFIC GENE POLYMORPHISMS. / NEIROPSYKhOBIOLOGIChNI MEKhANIZMY AFEKTYVNYKh I KOGNITYVNYKh ROZLADIV V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChORNOBYL'S'KII AES Z URAKhUVANNIaM POLIMORFIZMU GENIV.

Relevance of the present work is determined by the considerable prevalence of both affective and cognitive disor-ders 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 cog-nitive 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 andinternal control groups. The randomized sample of the male participants in liquidation of the consequences of theaccident (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 compar-ison group (n = 110) consisted of the unexposed patients of the Radiation Psychoneurology Department with thecorresponding age and sex (the external control group). The internal control group included the liquidators irradi-ated at doses < 50.0 mSv (n = 42). The standard diagnostic neuropsychiatric scales, psychodiagnostic questionnairesand 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 audito-ry cognitive evoked potentials (Event-Related Potentials, ERP) were applied. The genotypes of the serotonin trans-porter gene SLC6A4 were determined by the 5_HTTLPR and rs25531 polymorphisms. The methods of descriptive and vari-ation statistics, non-parametric criteria, regression-correlation analysis, survival analysis by Kaplan - Meier and riskanalysis were used.Results. Cerebrovascular diseases, organic mental and depressive disorders, mainly of radiation-stress-relatednature, prevail among the liquidators. The overall risk of neuropsychiatric pathology increases (Pv < 0.001) with theirradiation dose. The verbal memory and learning are impaired, as well as the full IQ is reduced at the expense of theverbal one. The frequency of both mild cognitive impairment and dementia is risen. The cognitive impairment atdoses > 0.3 Sv is dose-dependent (r = 0.4-0.7; p = 0.03-0.003). Affective disorders (depression) and neurocogni-tive 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 dis-turbed brain information processes lateralized to the Wernicke's area are observed even at doses > 50 mSv. The car-riers of intermediate and low-level genotypes (LА/S, LА/LG, LG/LG, LG/S, S/S) of the serotonin transporter gene SLC6A4have more depressive disorders, especially severe ones, and tend to have more frequent and severe cognitive andstress-related disorders.The debut of depressive disorders in the carriers of the intermediate and low-activity genotypes occurs much earli-er (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 ofthe human brain with a specific involvement of the hippocampus is considered to be the key cerebral basis of post-radiation organic brain damage. The association of genotypes by 5_HTTLPR and rs25531 polymorphisms of the SLC6A4gene with affective and cognitive disorders suggests the presence of neuropsychobiological features of these dis-orders associated with ionizing radiation depending on the certain gene polymorphisms.

Psychosocial state of the adult evacuees and risk factors of negative change. / SOTsIAL'NO PSYKhOLOGIChNYY̆ STAN DOROSLOGO EVAKUY̆OVANOGO NASELENNIa. FAKTORY RYZYKU NEGATYVNYKh ZMIN.

Numerous scientific studies have been carried out since the ChNPP accident indicating that the last one has caused a severe psychosocial stress in survivors. Population of radioactively contaminated territories, people migrated from the areas of strict radiation control, and accident consequences clean up participants in 1986 1987 were covered by the conducted research projects. Nature of the stress herewith is polygenic and includes factors directly related to the Chernobyl catastrophe, and factors being a result of social and economic circumstances. This report is devot ed to the results of research on psychosocial state of population evacuated from the 30 km zone of the ChNPP. OBJECTIVE: Study and evaluation of psychosocial state of population evacuated from the 30 km ChNPP zone at the age of 18 years and older; identification of potential psychosocial risk factors for the health loss. MATERIALS AND METHODS: The sampling epidemiological study of psychosocial state of population aged 18-50 years evacuated from the 30 km zone of ChNPP was conducted at the NRCRM Radiation Registry Outpatient Clinic and Radiation Psychoneurology Department. The study subjects (n=258) were mostly (98%) females. Study was con ducted from October 2013 till May 2015. All the sample members were registered since 1992 in the system of life long health monitoring, i.e. the NRCRM Clinical and Epidemiological Registry. Study subjects were interviewed through the method using an original «Questioning Inventory¼. Mathematical processing of study results was held using the Epi Info 7 software package. RESULTS: According to the study results, a nuclear accident at the Chornobyl NPP has become a powerful psychoso cial stress for evacuated people. Psychosocial state of the evacuees, formed during the post accident period, with full reason can be defined as a state of stable, chronic psychosocial stress. Nature of factors that caused the stress development is polygenic. Block of stressors directly related to the accident was determined, namely there were «change of radiation and ecological situation¼, «ionizing irradiation¼, «evacuation¼, and «radical breaking of dynamic stereotype of behavior and life¼. In parallel there was selected a block of stress factors generated by that background, i.e. psychological, social, economic, and cultural, on which a nuclear disaster was imposed upon. The effects of stress have manifested as a persistent syndrome of «anxiety¼ for the personal health and health of fami ly members, primarily the children, and as a stable state of «dissatisfaction¼ with fullness and quality of life. CONCLUSIONS: The nuclear accident at the ChNPP has been the cause of a strong psychosocial stress in adult evacu ated population, especially in women. Further in a remote period the stress was transformed into a stable, chronic form. Nature of stress is polygenic and includes stressors directly related to the accident, and stressors that are not directly related to the accident consequences, but are due to the level of social, economic, medical, and informa tional protection of survivors. Data presented in the paper are rather enough important for the formation of strate gies and measures for social and psychological protection of population in an event of nuclear accidents and incidents.

Social and psychological state of the Chornobyl clean up workers. Risk factors for negative changes. / SOTsIAL'NO PSYKhOLOGIChNYY̆ STAN UChASNYKIV LNA NA ChORNOBYL'S'KIY̆ AES. FAKTORY RYZYKU NEGATYVNYKh ZMIN.

It is generally recognized that the Chornobyl nuclear accident caused strong psychosocial stress affecting the entire population of Ukraine, primarily people involved in recovery operations. But what are the reasons? What is the struc ture of stressors? What are their social, medical and biological consequences, what are strategy and preventive meas ures? Issues that require special research and development. OBJECTIVE: To study social and psychological state of the Chornobyl cleanup workers 1986-1987, and to determine regularities of changes and dangerous risk factors. MATERIALS AND METHODS: On the basis of Polyclinic of Radiation Registry, NRCRM, we conducted sample epidemiolog ical study of social and psychological state of the Chornobyl clean up workers 1986-1987. We used method of inter viewing based on «questionnaire¼, specially developed for this purpose. The study was conducted in October 2013 - May 2015. The sample numbered 235 males aged 18-50 at the time of the accident. Their average age was (31.3 ± 5.3) years at the time of the accident and (58.9 ± 5.3) at the time of survey. RESULTS: The results revealed that the Chornobyl nuclear accident and its consequences caused strong social and psychological stress among clean up workers 1986-1987. We have identified a set of factors closely related to the Chornobyl accident, they have caused a sustainable development of mental syndrome - «Anxiety about their own health and the health of family members, especially children¼. The other set of stressors which are not closely relat ed to the Chornobyl accident but are the result of the social and economic, social and political situation in the coun try. However the former was found to be the cause of such a psychological state as «dissatisfaction with the com pleteness and quality of life¼. CONCLUSIONS: Social and psychological state of the Chornobyl clean up workers 1986-1987 is estimated as «poor¼ and it integrally can be characterized as a state of chronic psychosocial stress. Mental syndrome «Anxiety about per sonal health and the health of family members¼ and psychological syndrome «Dissatisfaction with living condi tions¼ are main consequences of this state. We identified the main stressors closely related to the consequences of the Chornobyl accident as well as those that are not related to the accident but affect profoundly the level of men tal, social and physical well being. Results of the research are of great importance in organization and provision of social, medical and antiradiation protection of population under emergency situations involving radiation exposure. Key words: Chornobyl accident, clean up workers, social and psychological state, risk factors.

Gene expression, telomere and cognitive deficit analysis as a function of Chornobyl radiation dose and age: from in utero to adulthood. / PORUShENNIa GENNOI EKSPRESII, TELOMER TA KOGNITYVNYY DEFITsYT IaK FUNKTsIIa DOZY U OPROMINENYKh IN UTERO TA V DOROSLOMU VITsI VNASLIDOK AVARII NA ChAES.

UNLABELLED: Objective - to estimate the possible effects of low dose ionizing radiation on human cognitive function in adult hood and in utero. MATERIALS AND METHODS: Cognitive tests, telomere length and expression of genes regulating telomere function were studied in Chornobyl cleanup workers who were exposed to doses under 500 mSv (n = 326) and subjects exposed in utero during the first days after the accident Prypiat town (n = 104). The neurocognitive assessment covered mem ory, attention, language, executive and visiospatial functions. In young adults after prenatal exposure a relation ship was analyzed between a cognitive function and radiation dose to foetus, brain and thyroid gland. Internal con trols were used for both groups - the group of Chornobyl cleanup workers exposed in doses less than 20 mSv and an age matched comparison group from radioactively contaminated areas for subjects exposed in utero. RESULTS: Cognitive functions in cleanup workers exposed to ionizing radiation at adulthood are characterized by symptoms of a mild cognitive impairment according to the MMSE (mean group score 25,58 ± 2,95) and a significant ly higher level of mental disorders according to the BPRS in a dose related manner. Cleanup workers exposed to doses over 500 mSv demonstrate a significant cognitive deficit in comparison with those exposed below 500 mSv and espe cially non exposed patients. Subjects exposed in utero during the check at age of 25-27 years exhibit an excess of the disorders of autonomic nervous system (ICD 10: G90). Neurological microsymptoms as well as neurotic, stress relat ed and somatoform disorders (F40-F48) dominate. Relationship were revealed between the TERT, TERF1, TERF2 genes expression, relative telomere length (RTL),cognitive deficit and cerebrovascular pathology, radiation dose and age. Telomere length in cleanup workers is sreduced after 50 years (6.1 %). The most significant reduction in telomere length is shown after 70 years (11.7 %). Negative correlation was found between telomere length and degree of cog nitive deficit (MMSE scale) and between age and degree of cognitive deficit. The RTL is significantly decreased in groups of persons with cognitive deficit compared to a comparison group. Telomere length at the late period after low dose radiation exposure is downregulated by the high TERF2 gene expression combined with low expression of TERT gene. After exposure to doses over 250-500 mSv a cognitive deficit and dementia were associated with a substantial increase in TERT gene expression, overexpression of TERF1 and decrease in expression of TERF2 gene. A relationship was revealed between the TERF2 gene expression and CD95+ cell fraction susceptible to apoptosis. CONCLUSIONS: This study shows that cognitive deficit in humans at a late period after radiation exposure is influ enced by dose, age at exposure and gene regulation of telomere function.