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Substance dependence is an readaptive state that develops from repeated drug administration, and which results in withdrawal upon cessation of drug use. A drug addiction, a distinct concept from substance dependence, is defined as compulsive, out-of-control drug use, despite negative consequences. An addictive drug is a drug which is both rewarding and reinforcing. FosB, a gene transcription factor, is now known to be a critical component and common factor in the development of virtually all forms of behavioral addiction and drug addictions.
Genetic factors
It has long been established that genetic factors along with social and psychological factors are contributors to addiction. A common theory along these lines is the self-medication hypotheses. Epidemiological studies estimate that genetic factors account for 40–60% of the risk factors for alcoholism. Similar rates of heritability for other types of drug addiction have been indicated by other studies.[8] Knestler hypothesized in 1964 that a gene or group of genes might contribute to predisposition to addiction in several ways. For example, altered levels of a normal protein due to environmental factors could then change the structure or functioning of specific brain neurons during development. These altered brain neurons could change the susceptibility of an individual to an initial drug use experience. In support of this hypothesis, animal studies have shown that environmental factors such as stress can affect an animal's genotype.
Overall, the data implicating specific genes in the development of drug dependence is mixed for most genes. One reason for this may be that the case is due to a focus of current research on common variants. Many addiction studies focus on common variants with an allele frequency of greater than 5% in the general population, however when associated with disease, these only confer a small amount of additional risk with an odds ratio of 1.1–1.3. On the other hand, the rare variant hypothesis states that genes with low frequencies in the population confer much greater additional risk in the development of disease.
GWAS studies represent the newest exploration into discovering associations between dependence, addiction, and drug use. These studies employ an unbiased approach to finding genetic associations with specific phenotypes and give equal weight to all regions of DNA, including tho