title: DRD4 and striatal modulation of the link between childhood behavioral inhibition and adolescent anxiety.
abstract: Behavioral inhibition (BI), a temperament characterized by vigilance to novelty, sensitivity to approach-withdrawal cues and social reticence in childhood, is associated with risk for anxiety in adolescence. Independent studies link reward hyper-responsivity to BI, adolescent anxiety and dopamine gene variants. This exploratory study extends these observations by examining the impact of DRD4 genotype and reward hyper-responsivity on the BI-anxiety link. Adolescents (N = 78) completed a monetary incentive delay task in the fMRI environment. Participants were characterized based on a continuous score of BI and the 7-repeat allele (7R+) of the DRD4 functional polymorphism. Parent-report and self-report measures of anxiety were also collected. Across the entire sample, striatal activation increased systematically with increases in the magnitude of anticipated monetary gains and losses. DRD4 status moderated the relation between BI and activation in the caudate nucleus. Childhood BI was associated with parent report of adolescent anxiety among 7R+ participants with elevated levels of striatal response to incentive cues. DRD4 genotype influenced the relations among neural response to incentives, early childhood BI and anxiety. The findings help refine our understanding of the role reward-related brain systems play in the emergence of anxiety in temperamentally at-risk individuals, building a foundation for future larger scale studies.
authors: Department of Psychology, Child Study Center, USB I, The Pennsylvania State University, University Park, PA 16802, USA. Tel: +1 814 865 9272; Fax: +1 814 863 7002. kxp24@psu.edu.
authors: Koraly
authors: K
authors: Pérez-Edgar
authors: Jillian E
authors: JE
authors: Hardee
authors: Amanda E
authors: AE
authors: Guyer
authors: Brenda E
authors: BE
authors: Benson
authors: Eric E
authors: EE
authors: Nelson
authors: Elena
authors: E
authors: Gorodetsky
authors: David
authors: D
authors: Goldman
authors: Nathan A
authors: NA
authors: Fox
authors: Daniel S
authors: DS
authors: Pine
authors: Monique
authors: M
authors: Ernst
mesh_terms: D000293:Adolescent; D001007:Anxiety / Q000150:complications / Q000235:genetics / Q000523:psychology; D003342:Corpus Striatum / Q000098:blood supply / Q000503:physiopathology*; D002658:Developmental Disabilities / Q000150:complications / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007266:Inhibition, Psychological; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics*; D010100:Oxygen / Q000097:blood; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012201:Reward; D057566:Self Report; D013694:Temperament; D055815:Young Adult
chemical_list: C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4; D010100:Oxygen
keywords: caudate; fMRI; genetics; reward; temperament