Substance Abuse

In the course of the study, it was found that when acute poisoning with ethyl alcohol and its surrogates, characteristic clinical signs of poisoning are observed, which depend primarily on the concentration (dose) of the poison taken and their physicochemical composition. Pathomorphological signs of poisoning with alcohol substitutes are pronounced dystrophic changes in all internal organs, with predominant liver and kidney dam-age.

Dysthymic disorders and a hangover of dependence on alkagol-this is the most observed condition. This condition requires in-depth clinical research and extensive analysis of the course of the disease. In modern psychiatry, the concept of comorbidity is widely used, on the basis of this concept lies the presence of two or more diseases in one patient. Since comorbidity prolongs the clinical picture of the disease, it complicates the diagnosis of the disease for doctors and requires special attention from doctors for treatment. Affektiv in drug-dependent patients, the importance of diagnosing disorders and distinguishing their variants is important. Rapid rational treatment measures arc required to relieve symptoms, otherwise affektiv treatment without eliminating pathology will be ineffective at any level of the disease.

The combination of alcoholism with depressive disorder is manifested by mild to moderate depressive disorder. Addiction to alcohol often leads to the development and reversal of depression. Depressive disorders also have a significant impact on the nature of alcohol dependence. Ethanol disrupts the metabolism of dopamine, a monoamine in the central nervous system and a neurotransmitter that is mainly involved in controlling the sensitive area. Therefore, the treatment and diagnosis of comarbitis cases with alcoholism and depressive disorders require separate study.

The article provides a catamnetic study of long-term outcomes in sick men and women with alcoholism and reveals gender differences.
The aim of the study is to identify a complex of clinical, socio-demographic factors affecting the formation of long-term outcomes of alcoholism, as well as to establish gender patterns.
An in-depth clinical follow-up study revealed noticeable differences in the dynamics of long-term outcomes in persons suffering from alcoholism: course variants, quality and duration of remissions, changes in social status and treatment effectiveness. According to the authors, premorbid socio-demographic and psychological factors can affect the timing of formation, types of course, the quality of remissions in patients with alcoholism and can serve as criteria for its prognosis.
In conclusion, the authors rightly note that in men and women, the clinical and pathogenetic mechanisms of alcoholism differ and this leaves an imprint on the outcomes of the disease.

The urgency and relevance of the theme of dissertation. According to the United Nations Office on Drugs and Crime1, the number of drug addicts is increasing year by year. In particular, if in 2006-2007 the number of drug addicts was 200 million, in 2013-2014, the number reached 246 million people. Annually alcoholism and its consequences cause death of approximately 2, 5 million people. Also, in some cases strong forms of it may cause such negative consequences as working capacity loss, conflicts with people around, and committing crimes. Therefore, nowadays the issue of deviant behavior is a serious social problem worldwide.
Since obtaining independence, Republic of Uzbekistan has achieved positive changes in the organization of up-to-date drug abuse services such as effective examination of patients with alcoholism and drug addiction, consultation, diagnosis and medical and social rehabilitation in the framework of large scale reforms.
Currently the whole world is paying special attention to exploration of interrelation of formation and development of alcoholism and opiate addiction with negative influence of deviant behavior in premorbid, effective ways of treatment and prevention measures. Due to this theoretical foundation of personal biological peculiar properties of patients with alcoholism and drug addiction, defining the importance of social-psychological factors of deviant behavior and deviant personality formation, comparative classification of clinical-dynamic features of pathological attraction and ncurovisual state of the brain of patients with alcoholism and opiate addiction with and without deviant behavior.
The dissertation research particularly addresses the tasks outlined in the government program “The year of a healthy child” signed by the President of the Republic of Uzbekistan, № PP-2133 on 19th of February in 2014 year, the decree of the President of the Republic of Uzbekistan "On efforts of further deepening the reform of the Healthcare system", № PP-1652, 28th of November 201 land the decree of the State commission of the Republic of Uzbekistan of the controlling of drugs “The program of complex methods against the drug violation and criminal turnover in 2011-2015 years”, No: 11/11 since 8th of August, 2011.
The aim of research work is examining clinical-psychopathological features of alcoholism and opium addiction in patients with deviant behavior in premorbid with consideration of personal-biological, social-psychological factors and improving trcatmcnt-and-rchabilitation and preventive measures.
The scientific novelty of the research work is as follows:
interference of existence of perinatal pathology in the anamnesis, prevailing of emotionally unstable and impulsive personality types, hereditary drug abuse inclination and mental illnesses major role in the formation of deviant behavior in patients with premorbid alcoholism and opiate addiction have been proved;
high progressive progress of addiction in patients with alcoholism and drug addiction with deviant behavior in premorbid, which in turn is associated with factors such as early onset of drug abuse, the rapid formation of dependence, severe course of abstinent syndrome;
it was established that at most of alcoholics and drug addicts with deviant behavior in a premorbid the reference high-progreduated course of dependence explained by the early beginning of the use drugs, high speed of formation and the heavy course of an abstinence syndrome.
the prevalence of behavioral and affective components of the pathological craving in patients with deviant behavior in premorbid has been justified;
morphological and structural changes in the brain, which vary from slight signs of an atrophy to expansion of subcortical space and furrows of bark of frontal lobes, as a result of high gradient progress of dependence in patients with deviant behavior have been identified;
the necessity of introducing cognitive-behavioral therapy to improve the social adaptation of patients with alcoholism and drug addiction with deviant behavior in premorbid has been pathogcnetically justified.
CONCLUSION
On the basis of the research on a doctoral thesis on “Role of the apoptosis factors for realization ofprotectivc-barricr function of the stomach mucosa and the intestine at the salmonella infection and chronic hepatitis” provided the following conclusions:
1. The particularity of deviant behavior in the premorbid of alcohol and opioid dependence is the prevalence of aggressive and delinquent behaviors, and what is more in the premorbid of alcohol dependent patients occurs more aggressive behavior and in opioid dependent patients more delinquent behavior. Both forms of behavior is characteristic mainly for explosive and unstable type of persons, whereas suicidal deviant behavior for hystcroid type personalities.
2. Among patients with alcohol and opioid dependence with deviant behavior in premorbide prevails psychopathic personality or accentual personalities with explosive and unstable types. Among patients without deviant behavior in the premorbid personality prevails psychasthenic and conformal type.
3. The formation of deviant behavior in patients with alcohol and opioid dependence have been developed due to the social and psychological factors including, to be brought up in incomplete families or families with low cultural level and material prosperity, upbringing defects likcless caring for children, cruelty and violence, getting involved with antisocial or criminal groups.
4. Clinical features ofalcohol and opioid dependence with deviant behavior in premorbide is early onset of psycho-active drug abuse, high progress of formation of abstinentsyndrome, the severity of abstinence, a highly progressive course of the disease with the rapid development of personality degradation and negative medical and social consequences.
5. In the same duration of the disease in patients with the presence of deviant behavior in the premorbid is morphostructural changes of the brain, ranging from minor atrophicstillto the expanding of subcortical space and sulci of the cortex of the frontal lobes, in patients without deviant behavior in premorbide - only the expansion of perivascular spaces, and problems with blood circulation in the veins.
6. Improving the treatment and rehabilitation measures of persons with deviant behavior in premorbide requires cognitive-behavioral psychotherapy methods for correcting deviations of personality and behavior.
7. When the developing of preventive measures for persons with deviant behavior must be considered the personality traits, social and psychological factors and clinical-dynamic features of the main disease with the definition of the form and direction of the work of performer.

Topicality and relevance of the theme of the dissertation. According to the UN Office on Drugs and Crime, in 2014 the total number of people in the world who used drugs was 247 million people aged 15 to 64 years, of these, about 10-13% arc the group suffering from drug addiction '. In addition, the number of opiate (opium, morphine and heroin) users totalled about 17 million people throughout the world, of these, 12 million arc injection narcotic users. The injection drug intake significantly contributes to the epidemic of viral hepatitis В and C in all parts of the world. According to the data of “The UN World Drug Report for 2016”, 1.6 million people who use injected drugs are infected with the human immunodeficiency virus, 6 million arc living with hepatitis C.
During the years of independence, as a result of systematic measures in the organization of drug treatment services in line with modem requirements, there were achieved positive changes in our country in rendering narcological medical assistance for the prevention and diagnosis of drug addiction, treatment and medical and social rehabilitation of drug addicts. According to the National Information and Analytical Centre for Drug Control of the Republic of Uzbekistan, the ratio of primary morbidity of drug abuse decreased 1.6 times in 2015.
At the global level, much attention is paid to the study of the role of personality-biological, social, psychological, clinical and psychopathological features, as well as a variety of pathophysiological and biochemical processes based on experimental studies in the pathogenesis and progression of opioid dependence with comorbid medical conditions for further optimization of rehabilitation measures. In this, the study of the features of comorbid somatic pathology in heroin addiction, in-depth studies of pathobiochcmical changes and optimization of treatment strategies to reduce the recurrence of the disease and to achieve sustainable remission is relevant and significant.
This dissertation research to a certain extent serves for the implementation of the tasks set out in the in the Government Program “The year of a healthy child” approved by Decree PD-2133 of the President of the Republic of Uzbekistan of 19 February 2014, the Decree PD-1652 of the President of the Republic of Uzbekistan “On measures to further deepen the reform of the health system” of 28 February 2011, the Resolution No.11/11 of the State Commission of the Republic of Uzbekistan on Drug Control “On the program of comprehensive measures to counter drug abuse and drug trafficking for 2011-2015” of 8 August 2011, the Resolution No. 01-14/47-17 “On the program of measures to counter drug abuse and drug trafficking for 2016-2020” of 17 June 2016, as well as in other legal normative and legal acts adopted in this area.
The aim of the research is determining the clinical, psychopathological and pathochemical aspects of opioid dependence with subsequent optimization of therapeutic approaches.
The scientific novelty of the research is as follows:
the relationship between premorbid social deviance, genetic predisposition to drug dependency and socio-psychological factors that contribute to the occurrence of comorbid somatic diseases (chronic viral hepatitis В and C) in individuals dependent on opioids has been proved;
features of the opium withdrawal clinical symptoms and craving for the drug, taking into account the comorbid somatic pathology (chronic viral hepatitis В and C) have been disclosed;
the effect of concomitant liver disease (chronic viral hepatitis В and C) on the intensity of systemic oxidative stress and significant reduction of antioxidant system in the blood of the patients with opioid dependence have been proved;
on the model of acute and chronic drug addiction, we defined the key link of pathogenesis characterized by prolonged increased generation of active oxygen forms in the subccllular fractions of liver and heart tissues on a background of the depletion of endogenous antioxidant defense and accumulation of protein degradation products - middle molecular peptides in the experiment;
based on the results of the experimental study, we pathogcnetically substantiated the necessity of the early inclusion of antioxidants in complex therapeutic measures in heroin addiction and the need for their depot in the liver in the treatment of drug addiction.
Conclusion
On the basis of the conducted studies on a doctoral dissertation “Clinical and pathogenetic aspects and optimization of therapeutic tactics in case of heroin addiction (clinical-experimental study)” the following conclusions are presented:
1. The most important socio-psychological factors that contribute to the emergence of comorbid somatic pathology of the liver (chronic viral hepatitis В and C) in patients who arc dependent on opioids arc: the early stages of the first trial of psychoactive substances (10,3%), early onset of systemic narcotization with a primary parenteral method of drug administration (31.5%), multiple drug use in the immediate vicinity (45.1%).
2. Comorbid somatic pathology of the liver (chronic viral hepatitis В and C) helps to increase the length and severity of the clinic of opium withdrawal syndrome due to the prevalence of psychopathological, algic, dissomnic disorders (34.6% versus 16.3% in the group of patients without comorbid pathology).
3. The distribution of the frequency of the pathological attraction to drugs revealed that the severe degree of the pathological attraction to drugs is characteristic of 36.9% of dependents on opioids with comorbid somatic pathology (chronic viral hepatitis В and C) and 8.6% of dependents on opioids without comorbid pathology, proving the contribution of the factor of comorbidity on the severity of the disease.
4. The study of personality characteristics revealed that drug users with chronic viral hepatitis В and C represent the individuals with severe difficulties in social adaptation, anxiety and depressive background of mood, which were often associated with the state of their physical health. The opioid dependents with comorbid disorders found external locus of control and arc characterized by personal immaturity, emotional and volitional characteristics, cognitive functions by detecting a correlation with the disease duration.
5. Comorbid pathology of the liver in opioid dependence contributes to significantly greater systemic oxidative stress and reduction of the antioxidant blood system. The intensity of the generation of reactive oxygen species in the blood of opioid-dependent people increases with the duration of narcotization and related liver disease, manifesting an increase of malondialdehyde, middle molecules of peptide and inhibition of catalase activity in relation to the control. The correlation analysis revealed a positive correlation with the duration of withdrawal symptoms in opioid-dependent people with comorbid pathology with increased values of middle molecules peptide (r=0.56) and negatively correlated with the activity of catalase (r=-0.66).
6. One of the molecular mechanisms of the pathogenesis of opioiddependent people is a pronounced oxidative stress, which manifests itself by prolonged increased generation of reactive oxygen species in the subccllular fractions of liver and heart tissues on the background of the depletion of endogenous antioxidant defense and accumulation of protein degradation products - middle molecules peptides. We established the trigger role of reactive oxygen species in the degradation of macromolecules of proteins in heart tissues, which indicates the development of prolonged endotoxemia and myocardial dysfunction even after the compensation of the oxidative stress, making it difficult for abstinence.
7. The optimized therapy including antioxidants - alpha-tocopherol acetate has a significant effect on the indicators of oxidative stress and antioxidant blood system of opioid- dependent people due to a lower level of malondialdehyde, catalase activity recovery to the control level. We substantiated the necessity of the early inclusion of antioxidants in complex therapeutic measures that can improve the therapy effectiveness, significantly reducing the duration of the opium withdrawal syndrome and the severity of craving for the drug.

The article studies the clinical and pathodynamic laws of clinical polymorphism and variants of the course of alcoholic delirium in patients with somatic diseases. Clinical psychopathological method examined 50 sick men with delirium tremens at the age of 31-60 years, in which somatic diseases were detected. As a result of the clinical and psychopathological analysis of alcohol delirium complicated by somatic diseases, three clinical options were identified: classic, mixed and severe. It should be noted that as alcohol delirium gets heavier, the clinical picture is transformed from simple to complex in the following regularity: illusions - hallucinations - confusion of varying degrees of consciousness - elements of mental automatism - movement disorders - amnesia of varying severity. The author concludes that somatic pathology, along with the main etiopathogenetic mechanism (alcohol), is involved in the clinical pathogenetic mechanisms of the formation of alcoholic delirium.

The Article studies the dynamics of immunological changes and correlated psychopharmacothcrapy of patients with alcoholism. Clinical immunological method examined 50 male patients with alcoholism at the age of 40-60 years, which determined the activity of autoantibodies to brain and liver cells.
During the period of acute intoxication, serum autoantibody concentration was within of 6,5±1,6 ng/ml. And after the combined treatment, autoantibodies fell to 2,1 ±0,7 ng/ml, that is more than 3 times lower. The effect of psychotropic medications on clinical and immunological processes was studied and revealed immunomodulating effect of tranquilizers and atypical neuroleptics.

Analysis of contemporary condition of the problem concerning tanatogcncsis study in intoxication and alcohol poisoning with selection of structural changes in the brain has been carried out.
It is underlined that changes in cerebrovascular system and nervous elements due to concentration of ethanol in the blood and tissues, its continuous usage, accompanying conditions (diseases, traumas, etc.) arc observed in the brain structures in alcohol intoxication and poisoning. According to the degree of evidence of pericellular and perivascular edema in various sections of the brain, the role of vascular and nervous structures in the tanatogcncsis in blood loss on the background of alcoholcmia is indicated.