The genetic basis of etiology and pathogenesis of Substance Dependence
The leading role of genetic factors (40-70%) with an additional modifying effect of environmental influences are indicated for diseases of substance dependence (alcohol, opiates, stimulants, cannabinoids and sedatives). Patophysiological substrate of the disease is mesocorticolimbic dopamine (DA) system of the brain - the neurochemical basis for the reinforcement system. DA system genes play a crucial role in the pathogenesis, form the genetic basis of hereditary predisposition and substantially control the personal and social domains within the framework of the biopsychosocial model of the disease. The most important factor in the pathogenesis serves individual level of genetic risk - the likelihood of developing the disease due to genetic reasons only. This indicator is the result of the joint effect of a significant number of genes with small effects, but their overall effect is considerable and can significantly influence on the age of onset, clinical dynamics and the level of treatment resistance. Implementation of genetic risk - the transition of probability in the fact of the disease, occurs with the participation of personal and social domains as «triggers» or «modifiers» of risk. Genetic profiling by polymorphic loci of DA system genes allows us to estimate the level of genetic risk and get the clinical prognosis of the disease trajectory. A high level of genetic risk is present in 11-15% of the population. Perhaps the level of genetic risk reflects the level of stability and dynamic agility of DA neuromediation in reinforcement system at the level of regulation of gene expression. In persons with a high level of genetic risk DA system initially in rigidity, it operates at the limit level, and any effects, such as stress factors, can lead to its decompensation. When substance abuse is began an irreversible rearrangement («pseudocompensation») of DA system in such person occurs, and now it becomes a sustainable and efficient if only a substance is present permanently in the body and the substance dependence is formed. Quantitative analysis of the genetic phenomenon of family loading, as the clinical manifestation of the level of genetic risk, is necessary to identify the clinical phenotype of the disease and find approaches to the differential diagnosis of hereditary forms of substance. Genetic profiling will help to solve the problem of increasing the efficiency and personalization of primary prevention, early diagnosis and personalized treatment of substance dependence disorders.