title: Dopaminergic variants in siblings at high risk for autism: Associations with initiating joint attention.
abstract: Younger siblings of children with autism spectrum disorder (ASD; high-risk siblings) exhibit lower levels of initiating joint attention (IJA; sharing an object or experience with a social partner through gaze and/or gesture) than low-risk siblings of children without ASD. However, high-risk siblings also exhibit substantial variability in this domain. The neurotransmitter dopamine is linked to brain areas associated with reward, motivation, and attention, and common dopaminergic variants have been associated with attention difficulties. We examined whether these common dopaminergic variants, DRD4 and DRD2, explain variability in IJA in high-risk (n = 55) and low-risk (n = 38) siblings. IJA was assessed in the first year during a semi-structured interaction with an examiner. DRD4 and DRD2 genotypes were coded according to associated dopaminergic functioning to create a gene score, with higher scores indicating more genotypes associated with less efficient dopaminergic functioning. Higher dopamine gene scores (indicative of less efficient dopaminergic functioning) were associated with lower levels of IJA in the first year for high-risk siblings, while the opposite pattern emerged in low-risk siblings. Findings suggest differential susceptibility-IJA was differentially associated with dopaminergic functioning depending on familial ASD risk. Understanding genes linked to ASD-relevant behaviors in high-risk siblings will aid in early identification of children at greatest risk for difficulties in these behavioral domains, facilitating targeted prevention and intervention. Autism Res 2016, 9: 1142-1150. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
authors.affiliation: Department of Psychology, University of Miami, Florida.|MIND Institute, University of California, Davis, California.
authors.forename: Devon N
authors.initials: DN
authors.lastname: Gangi
authors.affiliation: Departments of Psychology, Pediatrics, Electrical & Computer Engineering, and Music Engineering, University of Miami, Florida.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Messinger
authors.affiliation: University of Miami Miller School of Medicine and Hussman Institute for Human Genomics, Florida.
authors.forename: Eden R
authors.initials: ER
authors.lastname: Martin
authors.affiliation: University of Miami Miller School of Medicine and Hussman Institute for Human Genomics, Florida.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cuccaro
mesh_terms: D001288:Attention; D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004298:Dopamine / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D018570:Risk Assessment; D035781:Siblings
chemical_list: C581293:DRD2 protein, human; C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D004298:Dopamine
keywords: autism spectrum disorder; differential susceptibility; dopamine; high-risk siblings; initiating joint attention