Molecular genetic underpinnings of human substance abuse vulnerability: likely contributions to understanding addiction as a mnemonic process.
Classical genetic studies document strong complex genetic contributions to abuse of multiple addictive substances. These genetic influences are more prominent in the later phases of individuals' progressions toward substance dependence. Individual differences in human addiction vulnerability could thus derive, in part, from individual differences in mnemonic systems. These variations could add to allelic variations that could produce effects on addiction vulnerability phenotypes by other routes that could include (1) differences in drug metabolism or biodistribution, (2) differences in drug's rewarding properties, (3) differences in traits manifest by the addict, including personality differences and (4) differences in the addict's psychiatric comorbidities. Data from linkage and association genome scans now identify chromosomal regions that are likely to contain allelic gene variants that contribute to human addiction vulnerability. Converging positive results are found in several different substance-abusing populations studied in several laboratories. This convergence supports the idea that common allelic variants contribute to individual differences in vulnerability to substance dependence. Genomic markers that identify allelic variants that reproducibly alter addiction vulnerability in several populations provide tools for research in addictions, tools to improve addiction treatments, tools to improve addiction prevention, clues to the genetic bases of individual differences in mnemonic processes and clues to the genetic bases of individual differences in the other traits and disorders that co-occur with substance dependencies.
Uhl
George R
GR
Molecular Neurobiology Branch, NIDA-IRP, NIH, Box 5180 Baltimore, MD 21224, USA. guhl@intra.nida.nih.gov
D000483:Alleles; D000818:Animals; D003001:Cloning, Molecular; D004777:Environment; D006801:Humans; D007858:Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D019966:Substance-Related Disorders / Q000235:genetics*