Publication Date

2015-04-30

Availability

Embargoed

Embargo Period

2017-04-29

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Psychology (Arts and Sciences)

Date of Defense

2015-04-01

First Committee Member

Daniel S. Messinger

Second Committee Member

Heather A. Henderson

Third Committee Member

Jennifer C. Britton

Fourth Committee Member

Eden R. Martin

Fifth Committee Member

Michael L. Cuccaro

Abstract

Infant siblings at risk for Autism Spectrum Disorder (ASD; high-risk siblings) exhibit lower levels of joint attention and higher levels of behavior problems than low-risk siblings (siblings with no family history of ASD), but also exhibit high levels of variability in these domains. The neurotransmitter dopamine is linked to brain areas associated with attention, reward, and motivation. Common genetic variants affecting dopamine neurotransmission, DRD4 and DRD2, have been associated with attention difficulties and behavior problems in typically developing children. We examined whether these variants explain variability in ASD-relevant behaviors in high-risk siblings. DRD4 and DRD2 genotypes for high-risk and low-risk siblings were coded according to dopaminergic functioning to create a gene score, with higher scores indicating more alleles associated with lower dopaminergic functioning. Initiating joint attention (IJA) was observed in the first year, and parents reported behavior problems at 3 years using the Child Behavior Checklist. Dopamine gene scores indicative of lower dopaminergic functioning were associated with less optimal behavior in the first year (lower levels of IJA) and at 3 years (higher levels of internalizing problems) for high-risk siblings, while the opposite pattern typically emerged in low-risk siblings. Lower dopaminergic function was associated with poorer referential communication and increased behavior problems only in the presence of familial risk for ASD. Findings suggest differential susceptibility—children’s ASD-relevant behaviors were differentially affected by dopaminergic functioning depending on their familial risk for ASD. Understanding genes linked to ASD-relevant behavioral difficulties in high-risk siblings will aid in the very early identification of children at greatest risk for such difficulties, opening the way for targeted prevention and intervention protocols.

Keywords

high-risk siblings; dopamine; DRD4; DRD2; initiating joint attention; behavior problems

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