The Role of Dopaminergic Variants in Initiating Joint Attention in High- and Low-Risk Siblings

Background:  The capacity to use gaze and gesture to share experiences or events with a social partner, initiating joint attention (IJA), typically emerges during the first year of life.  Deficits in IJA are a core impairment in children with Autism Spectrum Disorder (ASD), and IJA may be a particularly important skill for infants at risk for ASD (high-risk siblings; younger siblings of children diagnosed with ASD).  Levels of IJA at 8 months have predicted later ASD symptom severity at 30 months in high-risk siblings (Ibañez, Grantz, & Messinger, 2012).  This suggests that the ability to share attention with a social partner before one year is particularly important for high-risk siblings in the development of ASD symptomatology.  However, high-risk siblings exhibit substantial behavioral heterogeneity, both in early levels of IJA and in later ASD symptomatology.

Objectives:  We aimed to explain variability in early levels of IJA by examining the role of common dopaminergic genes, DRD4 and DRD2—variants that have been associated with attention problems in children.

Methods:  High-risk siblings (n = 55, 35 male) and low-risk siblings (n = 38, 16 male) were genotyped for DRD4 and DRD2.  Each infant was assigned a dopamine gene score (ranging from 0-2) reflecting the number of genotypes associated with less efficient dopaminergic functioning (7-repeat allele of DRD4 and A allele of DRD2) (Pearson-Fuhrhop, Minton, Acevedo, Shahbaba, & Cramer, 2013).  Infants were administered the Early Social Communication Scales (ESCS) at 8, 10, and 12 months, a semi-structured interaction with an examiner during which a series of toys are presented and activated.  Rates per minute of IJA were calculated for each assessment age; a mean was then calculated from the standardized values of each assessment age to provide a measure of IJA in the first year for analyses.

Results:  A regression model indicated a dopamine score*status interaction effect, b = -0.81, t = -3.09, p = .003.  Regression analyses by risk group indicated that in high-risk siblings, IJA levels decreased as dopamine scores increased (indicative of less efficient dopaminergic functioning), b = -0.31, t = -2.03, p = .047, while in low-risk siblings, IJA levels increased as dopamine scores increased, b = 0.50, t = 2.35, p = .03 (see Figure 1).

Conclusions:  Higher dopamine scores, indicative of less efficient dopaminergic functioning, were associated with lower early levels of IJA in high-risk siblings.  Low-risk siblings exhibited the opposite pattern, suggesting differential susceptibility.  In the presence of familial risk for ASD, less efficient dopaminergic function was associated with lower IJA levels.  Links between common genetic variants and behavioral phenotypes can aid in understanding developmental heterogeneity within high-risk siblings.  Knowledge of genotypes in high-risk siblings associated with areas of difficulty relevant to ASD, such as IJA, may aid in assessing risk and identifying siblings at the greatest potential need for early interventions.