Vulnerability to Substance Abuse.

Vulnerability to develop dependence on an addictive substance is a common phenotype. It receives pathogenic components from genetic predispositions, brain memory systems, brain reward systems, the acute and chronic properties of addictive substances themselves and environmental features that come largely from outside of the home environment. Here we review: (a) evidence that supports polygenic models with (at least) modest heterogeneity for the genetic architectures of addiction and related phenotypes; (b) the data that shape our current understanding of the molecular genetics of individual differences in vulnerability to substance dependence and related phenotypes in individuals of European, African and Asian ancestries; (c) overlaps between addiction vulnerability and data for other heritable, brain-based phenotypes that include: (i) bipolar disorder, (ii) cognitive ability, (iii) frontal lobe brain volume, (iv) ability to successfully quit smoking, (v) neuroticism, and (d) plausible ideas about the history of at least some of the allelic variants that predispose to addictions in current populations. These convergent results add to evidence that individual differences in the quality and quantity of brain connections make pleiotropic contributions to individual differences in vulnerability to addictions and to related brain disorders and phenotypes. [ABSTRACT FROM AUTHOR]