title: Longitudinal predictors of cannabis use and dependence in offspring from families at ultra high risk for alcohol dependence and in control families.
abstract: Cannabis use is common among adolescents. Identification of the factors associated with continued heavy use into young adulthood and development of cannabis abuse and dependence is of considerable importance. The role of familial risk for addiction and an associated endophenotype, P300 amplitude, has not previously been related to cannabis use and dependence. A prospective longitudinal study spanning childhood and young adulthood provided the opportunity for exploring these factors, along with genetic variation, in the cannabis use behaviors of 338 young adult offspring from high and low familial risk for alcohol dependence families (ages 19-30). P300 data were collected multiple times in childhood. The association between young adult patterns of cannabis use or cannabis abuse/dependence was tested with genetic variation in the cannabinoid gene, CNR1, the ANKK1-DRD2 gene, and childhood developmental trajectories of P300. Young adult patterns of cannabis use was characterized by three patterns: (i) no use throughout; (ii) declining use from adolescence through young adulthood; and (iii) frequent use throughout. Following the low P300 trajectory in childhood predicted cannabis abuse and dependence by young adulthood. A four SNP ANKK1-DRD2 haplotype (G-G-G-C) was found to be significantly associated with the frequency of use patterns (P = 0.0008). Although CNR1 variation overall was not significantly associated with these patterns, among individuals with cannabis abuse/dependence the presence of one or both copies of the rs806368 A > G minor allele conferred a 5.4-fold increase (P = 0.003) in the likelihood that they would be in the frequent and persistent use group rather than the declining use group.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Shirley Y
authors.initials: SY
authors.lastname: Hill
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Bobby L
authors.initials: BL
authors.lastname: Jones
authors.affiliation: VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Steinhauer
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Zezza
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Scott
authors.initials: S
authors.lastname: Stiffler
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000437:Alcoholism / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D018913:Event-Related Potentials, P300; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D002189:Marijuana Abuse / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008957:Models, Genetic; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D043882:Receptors, Cannabinoid / Q000235:genetics; D012307:Risk Factors
chemical_list: D043882:Receptors, Cannabinoid
keywords: CNR1; D2; cannabis abuse; cannabis dependence; cannabis use