The genetics of alcoholism.
Heritability estimates for alcoholism range from 50% to 60%, pointing out the importance of genetic and environmental factors in its etiology. This review highlights recent advances in translational work investigating genetic influences on alcoholism. We focus on genetic research involving corticotropin-releasing factor, glutamatergic, and opioidergic systems. Variation in the CRF1 receptor gene has been shown to moderate stress-induced alcohol drinking (gene-environment interaction) in animals, and this finding was recently extended to humans. Also, the hyperglutamatergic state, first observed during withdrawal from chronic alcohol exposure in animal models, is associated with aversive and dysphoric states in alcoholics. Pharmacogenetic studies of naltrexone efficacy are in the clinical stages, and recent studies confirmed a differential response dependent on the mu-opioid receptor genotype. Such advances will be essential for the effective treatment of alcoholism in the future.
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, P. O. Box 80, London SE58AF, England.
David
D
Stacey
Toni-Kim
TK
Clarke
Gunter
G
Schumann
D000437:Alcoholism / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D004195:Disease Models, Animal; D018846:Excitatory Amino Acids / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D051379:Mice; D009271:Naltrexone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics; D012931:Social Environment; D013315:Stress, Psychological / Q000150:complications / Q000235:genetics; D000099052:CRF Receptor, Type 1
D018846:Excitatory Amino Acids; D009292:Narcotic Antagonists; D018019:Receptors, Corticotropin-Releasing Hormone; D017450:Receptors, Opioid, mu; D000099052:CRF Receptor, Type 1; D009271:Naltrexone; D003346:Corticotropin-Releasing Hormone