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Epidemiology and molecular studies in cerebrovascular disease at the late period after radiation exposure in Chornobyl
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Consensus on the radiation effects in cardiovascular system doesn't exist. More evidence is needed to conclude whether or not radiation exposure has increased the incidence of cardiovascular and cerebrovascular disease, and associated mortality. The observed excess of cerebrovascular diseases is linked to those having worked during the first six months and having cumulated doses of more than 150 mSv. Although these results are statistically compatible with those of the atomic bombings survivors study, they could only be regarded as preliminary. Latest hibakusha data supposes an increase in mortality. Industrial cohorts' studies have controversial results. According to UNSCEAR, "There are deterministic effects, such as cataracts or cardiovascular disease, for which radiation exposure is not the only known cause. If these effects occur, usually some time after high levels of exposure, and there is no specific marker for radiation exposure having caused them, it is not possible to attribute the effect with certainty to radiation exposure, but only to express a probability that radiation was wholly or partly the cause,"[1]. The existing level of knowledge allows considering the contributive role of the immune function changes of the late period after irradiation to the cerebrovascular pathology pathways. Therefore, it is also actually taking into account an interaction between the immune and nervous systems. Encephalopathy ("radiation encephalopathy", "discirculatory encephalopathy"- DEP, "demielinisation" encephalopathy) according to medical statistics is one of the most common disorders of a late period after irradiation and one of the most frequent diagnosis for establishing a causal connection of disease with a radiation factor. At the same time, the nature of this disorder is not identified, and many researchers do not recognize it as an effect of irradiation. In some studies it was depicted as a result of direct brain tissue radiation damage, or as an indirect effect due to damage of vascular circulation. Development of the brain pathology as a result of CVD and vegetative dysfunctions, and the substantial vasculatory changes revealed in encephalopathy patients provide support to a latter assumption. More evidence is needed to conclude whether or not radiation exposure has increased the incidence of cardiovascular and cerebrovascular disease and associated mortality [1].
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... На підставі аналізу даних Клініко-епідеміологічного реєстру (КЕР) ННЦРМ та Державної установи "Український центр інформаційних технологій та Національного Реєстру МОЗ України" (ДРУ), отримані епідеміологічні докази збільшення частоти психічних розладів, а також цереброваскулярної патології, включаючи збільшення смертності від інсультів, в учасників ЛНА за наявності радіаційних ризиків при дозах >0,25-0,5 Гр з урахуванням традиційних чинників ризику [30,38,47,64]. У дорослих евакуйованих з Чорнобильської зони відчуження при дозах опромінення щитоподібної залози більше 0,3 Гр зростає ризик виникнення цереброваскулярної патологіі, а при дозах більше 2 Гр -психічних розладів. ...
... У дорослих евакуйованих з Чорнобильської зони відчуження при дозах опромінення щитоподібної залози більше 0,3 Гр зростає ризик виникнення цереброваскулярної патологіі, а при дозах більше 2 Гр -психічних розладів. Смертність учасників ЛНА від хвороб системи кровообігу збільшується при дозах більше 0,25 Гр, особливо в осіб молодого віку [30,38]. Даний факт узгоджується з результатами наших досліджень щодо більшої вразливості до опромінення молодих дорослих (до 35 років) на момент експозиції. ...
... Сьогоднішній рівень знань свідчить про доказану роль порушень імунної системи у патогенезі цереброваскулярної та іншої цереброорганічної патології у віддалений період після опромінення [38]. ...
There is an international consensus on the long-term adverse consequences for mental health of survivors of the radiation accidents as in Chornobyl and Fukushima Daiichi. The goal was to summarize the results of almost 30 years of neuropsychiatric studies of different categories of survivors, who performed in the Department of Radiation psychoneurology, Institute of Clinical Radiology, State Institution “National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine”, in the context of current radiobiologic and neuropsychiatric challenges. The main cerebro-organic consequences of the Chornobyl disaster include brain damage (cerebrovascular pathology, neurocognitive deficits, demyelinating diseases of the nervous system, paroxysmal states) and neuropsychiatric effects in the developing brain. Radiocerebral effects of low doses of ionizing radiation, especially, cerebrovascular pathology and cognitive impairment, are at the focus of research around the world. A growing body of evidence suggests the radiosensitivity of the central nervous system. Cortico-limbic system is a target for radiation damage to the brain, where the dysfunction of hippocampal neurogenesis is crucial. It requires further high-tech neuropsychiatric studies of radiation effects at different exposure scenarios.
... In 2006, the UN Chernobyl forum identified the impact on mental health as a major problem following the ChNPP disaster, in particular, the increased prevalence of stress-related disorders, effects on developing brain, organic mental disorders and suicides, as well as cardiovascular and cerebrovascular disorders mainly in liquidators (Azizova et al., 2014;Bazyka et al., 2015;Bennett et al., 2006). Subsequently, the impact on mental health and neuropsychiatric consequences of the Chernobyl disaster was broadened and outlined as follows: 1) psychological and psychosomatic disorders; 2) long-term mental health disorders, including depression, post-traumatic stress disorders (PTSD), and alcohol abuse; 3) cerebrovascular and other organic disorders of the central nervous system (CNS), 4) cognitive disorders; 5) effects on the developing brain; 6) potential radiocerebral effects; 7) chronic fatigue syndrome; 8) suicide. ...
Objective: The Chernobyl nuclear power plant (ChNPP) disaster that happened in Ukraine on the 26th of April 1986 still represents the most severe nuclear accident in human history. Its consequences, especially those involving mental health are increasingly emerging as long-term detrimental effects. Therefore, the aim of the present paper was to review the results of some of authors’ studies and their personal reflections on this topic.
Method: The authors selected and commented on the findings mainly derived from their contributions on the prevalence of long-term psychopathological symptoms and neuropsychiatric disorders in different groups of exposed and non exposed individuals, including the workers at the NPP the so-called liquidators (CUWs), the most exposed group, evacuees and people living in more or less contaminated areas.
Results: The main findings derived from a series of studies carried out by the authors throughout the following decades after the disaster indicate the high prevalence of cerebrovascular diseases, organic mental and depressive disorders, cognitive impairment and even dementia that increase with the irradiation dose mainly amongst the liquidators. The organic disorders are probably related to a peculiar effect of radiation on left, dominant brain hemisphere. Interestingly, recent studies revealed abnormalities of the serotonin transporter and other genes disorders possibly at the basis of depression of exposed individuals.
Conclusions: The high prevalence of neuropsychiatric disorders amongst irradiated subjects following the ChNPP disaster highlights the impact of radiation exposure on the lifelong onset of neuropsychiatric disorders, for too long neglected by international agencies. Such findings require to be deepened in the future possibly within the frame of the so-called “ecological psychiatry”.
... New data on neurobiological mechanisms sup porting the human brain radiosensitivity and the pathogenesis of various radiocerebral effects is being acquired including as follows: inhibition of neurogenesis, mainly in the hippocampus; telo mere length and gene expression changes; apopto sis; neuroinflammation; autoimmune processes; «vascular glial union»; multi organ dysfunction, etc. [14][15][16]. In the 7 th EU Framework Program «Nuclear Fission and Radiation Protection», a сonjoint European project CEREBRAD, Cognitive and Cerebrovascular Effects Induced by Low Dose Ionizing Radiation, in which we partic ipated, the clinical and modern molecular biolo gical features of low dose irradiation cognitive and cerebrovascular effects were found [17][18][19]. ...
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. 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.
... В настоящее время появились новые доказательства радиочувствительности го ловного мозга при воздействии ионизиру ющих излучений даже в малых дозах, глав ным образом из за радиоуязвимости гип покампального нейрогенеза, процессов апоптоза, изменений нейросигналирова ния, теломер/теломеразного комплекса, профиля экспрессии генов, нейровоспале ния, аутоиммунных реакций и др. Любое из нарушений в этом спектре может повлиять на головной мозг и психическое здоровье после воздействия ионизирующей радиа ции (Nyagu A.I., Loganovsky K.N., 1998;Cucinotta F.A. et al., 2009;Loganovsky K., 2009;Picano E. et al., 2012;Bazyka D. et al., 2015;Marazziti D. et al., 2016;Loganovsky K. et al., 2018;Tang F.R., Loganovsky K., 2018). Тем не менее, есть и сообщения о благо приятном воздействии на здоровье иони зирующих излучений в малых дозах, как «радиоадаптивном ответе» (Rodgers B.E., Holmes K.M., 2008). ...
... В настоящее время появились новые доказательства радиочувствительности го ловного мозга при воздействии ионизиру ющих излучений даже в малых дозах, глав ным образом из за радиоуязвимости гип покампального нейрогенеза, процессов апоптоза, изменений нейросигналирова ния, теломер/теломеразного комплекса, профиля экспрессии генов, нейровоспале ния, аутоиммунных реакций и др. Любое из нарушений в этом спектре может повлиять на головной мозг и психическое здоровье после воздействия ионизирующей радиа ции (Nyagu A.I., Loganovsky K.N., 1998;Cucinotta F.A. et al., 2009;Loganovsky K., 2009;Picano E. et al., 2012;Bazyka D. et al., 2015;Marazziti D. et al., 2016;Loganovsky K. et al., 2018;Tang F.R., Loganovsky K., 2018). Тем не менее, есть и сообщения о благо приятном воздействии на здоровье иони зирующих излучений в малых дозах, как «радиоадаптивном ответе» (Rodgers B.E., Holmes K.M., 2008). ...
... The EEG theta-range spectral power decrease (especially in the left frontotemporal zone), beta-activity amplification with lateralization to the dominant hemisphere as well as abnormalities of a normal asymmetry of visual evoked potentials and the vertex potential can be considered the neurophysiologic markers of a prenatal radiation (Figures 22, 23). The relatively late gestation term (weeks [16][17][18][19][20][21][22][23][24][25] is the most critical period for cerebrogenesis under the nuclear reactor accident followed by an intensive environmental release of radioactive iodine compared to the circumstances of a uniform external radiation (weeks [8][9][10][11][12][13][14][15]. The incidence of the organic mental disorders, psychological development abnormalities, paroxysmal states (headache, migraine, and epileptiform syndromes), somatoform autonomous dysfunction, childhood behavioral and emotional disorders was higher in children and adolescents prenatally irradiated after the Chornobyl accident. ...
Psychophysiological assessment of the brain is very sensitive to detection of ionizing radiation effects. There are new evidences of the brain radiosensitivity even to low doses, mainly, due to radiovulnerability of hippocampal neurogenesis. According to our recent data, the changes of cognitive functioning are registered by Event Related Potentials (ERP) even at such very low radiation doses as 0.05 Gy (5 rad). This psychophysiological dose threshold is corresponding to radiation background and is dramatically lower of radiation exposure during space flights, especially long-term. Current challenges of modern society includes threat of radiation emergencies (radiation accident at nuclear power plants (NPP), nuclear war and nuclear terrorism (in particular, using of the radiological dispersal device, RDD), long-term space travel planning, specifically to Mars, etc. Psychophysiological technologies are very effective and safe for radiation effects detection.
This chapter integrates our own 30-years’ experience and available data concerning changes spontaneous and evoked cerebral bioelectrical activity and cognitive functions in humans and animals following exposure to ionizing radiation. The contemporary radiobiological problems on human central nervous system (CNS) radiosensitivity and accelerated aging of the brain influenced by low doses of ionizing radiation is particularly discussed. A comprehensive analysis of psychophysiological evidence to support both hypotheses had been performed, and the necessity of a new research field (radiation psychophysiology) development was substantiated.
The paper constitutes a thorough discussion on multiple psychophysiological effects at different exposure scenarios (acute radiation sickness (ARS), chronic exposure at low doses range, persons exposed in utero and at the age of 0-1 years). The cortico-limbic system, mainly of the left, dominant hemisphere is considered as a primary target for ionizing radiation which may be the neurophysiological basis of schizophrenia-like symptoms. A new possible radiocerebral effect in Wernicke’s area is shown. In the present chapter psychophysiological approach is considered in terms of its evolutionary perspective: routine EEG, quantitive EEG (qEEG), multisensory evoked potentials (SSEP, AEP, BAEP, VEP, SSR, VestEP), event-related potentials (ERP). The great emphasis is placed on the methodology of cognitive evoked potentials P300.
Keywords: psychophysiology, ionizing radiation, low doses, qEEG, brain mapping, evoked potentials, ERP
Background:
Depopulation processes in Ukraine have been affected by the Chornobyl catastrophe (ChC), but therate of demographic aging of survivors remains uncertain. Although the mental health disorders of the survivors arerecognized internationally, problems of their research remain unresolved. Thus, these areas of research are relevant.Objective is to determine the rate of demographic aging of survivors of the Chornobyl NPP (ChNPP) accident and toanalyze the state of their mental health survey, outlining solutions.
Materials and methods:
Information and statistical sources for 1986-2019 of the Ministry of Health of Ukraine andthe State Statistics Service of Ukraine on the age of the ChC survivors are used. The results of previous own researchand other scientists using the data of the Clinical and Epidemiological Register (CER) of the State Institution«National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine»(NRCRM), the State Register of ChC survivors (SRU), and the Department of Radiation Psychoneurology, Institute ofClinical Radiology, NRCRM are integrated. Theoretical, general scientific, demographic and mathematical-statisticalresearch methods and documentary analysis are used.
Results:
It is shown that in 2018, compared to 1995, the number of the ChC survivors, who are under the supervi-sion of the Ministry of Health of Ukraine, decreased by almost 987 thousand. The part of people born from personsof the 1st-3rd accounting groups increased in the structure of survivors (from 13.1 % in 1995 to 13.6 %), and thisdecreased in persons living or lived in the territories subject to supervision (75.1 % and 63.1 %, respectively), butin evacuees and Chornobyl clean-up workers (liquidators) this did not change significantly. A high level of aging ofthe ChC survivors (except for the 4th group) is revealed: liquidators - 59.0 %; evacuees - 25.0 %, and residents ofradioactively contaminated territories (RCT) - 30.7 %. It has been proved that the countries of RCT differ signifi-cantly in the number of the ChC survivors and their structure. The increase in the post-accident period indicators ofthe level of aging and the average age of the RCT population indicates negative changes in age parameters and theneed to continue research to identify factors «responsible» for such changes. Long-term mental health disordersand neuropsychiatric effects in the ChC survivors have been identified - an excess of cerebrovascular pathology andneurocognitive deficits, especially in liquidators, which may indicate an accelerated aging. Radiation risks havebeen revealed for acute and chronic cerebrovascular pathology and organic mental disorders of non-psychotic andpsychotic levels. Neurophysiological and molecular-biological atypia of aging processes under an exposure to lowdoses of and low dose rate of ionizing radiation have been found. The psyche under the age of 40 years old at thetime of exposure is more vulnerable. Existing statistical and registry data underestimate the level of mental disor-ders in the population of Ukraine, including the ChC survivors by an order of magnitude.
Conclusions:
The ChC survivors are aging in the country. The negative tendencies in age parameters of survival indi-cate the need to continue research to identify the factors «responsible» for such changes. Mental health disordersand neuropsychiatric effects in the ChC survivors are underestimated. It is necessary to create a national psychiatricregistry of Ukraine and long-term (lifelong) monitoring of survivors with well-planned clinical and epidemiologicalstudies of general and mental health with reliable dosimetric support based on national registries using the latest information technologies.
Background:
Exposure to ionizing radiation could affect the brain and eyes leading to cognitive and vision impairment, behavior disorders and performance decrement during professional irradiation at medical radiology, includinginterventional radiological procedures, long-term space flights, and radiation accidents.
Objective:
The objective was to analyze the current experimental, epidemiological, and clinical data on the radiation cerebro-ophthalmic effects.
Materials and methods:
In our analytical review peer-reviewed publications via the bibliographic and scientometric bases PubMed / MEDLINE, Scopus, Web of Science, and selected papers from the library catalog of NRCRM - theleading institution in the field of studying the medical effects of ionizing radiation - were used.
Results:
The probable radiation-induced cerebro-ophthalmic effects in human adults comprise radiation cataracts,radiation glaucoma, radiation-induced optic neuropathy, retinopathies, angiopathies as well as specific neurocognitive deficit in the various neuropsychiatric pathology including cerebrovascular pathology and neurodegenerativediseases. Specific attention is paid to the likely stochastic nature of many of those effects. Those prenatally and inchildhood exposed are a particular target group with a higher risk for possible radiation effects and neurodegenerative diseases.
Conclusions:
The experimental, clinical, epidemiological, anatomical and pathophysiological rationale for visualsystem and central nervous system (CNS) radiosensitivity is given. The necessity for further international studieswith adequate dosimetric support and the follow-up medical and biophysical monitoring of high radiation riskcohorts is justified. The first part of the study currently being published presents the results of the study of theeffects of irradiation in the participants of emergency works at the Chornobyl Nuclear Power Plant (ChNPP).
Recently, an increasing interest has been directed towards the investigation of brain effects of ionizing radiation (IR), as it is now evident that, depending on the doses, the damages character and severity, as well as clinical manifestations are different. They are generally considered to be the result of a blending of atherosclerotic, cardiovascular, cerebrovascular and neurodegenerative processes. Further, an ongoing debate has been opened on the possible brain abnormalities following medical radiation from X-ray in interventional radiology and nuclear medicine procedures that would involve both patients and medical workers. The aim of the present paper is to summarize literature data on brain effects of IR exposure, with a special focus on those gathered by some of the authors after the Chornobyl nuclear plant disaster, and how they can be related to the pathophysiology of different neuropsychiatric disorders.
Key words: ionizing radiation, brain, Chornobyl disaster, neuropsychiatric disorders, neurogenesis, hippocampus, neuroinflammation, atherosclerosis
To study the effect on lung cancer incidence of a long exposure to low levels of radon, 500 male 3-month-old Sprague-Dawley rats, were exposed to a cumulative dose of 25 WLM of radon and its daughters, 6 hours a day, 5 days a week, during 18 months. Exposure conditions were controlled in order to maintain a defined PAEC: 42 x 10⁻⁶ J.m⁻³ (2 WL), in the range of domestic and environmental exposures. Animals were kept until they died or given euthanasia when moribund. Mean survival times were similar in both irradiated and control groups: 828 days (SD = 169) and 830 days (SD = 137), as well as lung cancer incidence, 0.60% at 25 WLM and 0.63% for controls. The incidence of lung lesions was compared statistically with controls and those previously obtained at cumulative exposures of 25 and 50 WLM delivered over a 4-6 month period, inducing a significant increase of lung cancer, 2.2% and 3.8% respectively. Such a comparison showed a decreased lung cancer incidence related to a decrease in the dose rate for low levels of radon exposure.
