Joint attention in infants at high familial risk for autism spectrum disorder and the association with thalamic and hippocampal macrostructure

Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder. Infants diagnosed with ASD can show impairments in spontaneous gaze-following and will seldom engage in joint attention (JA). The ability to initiate JA (IJA) can be more significantly impaired than the ability to respond to JA (RJA). In a longitudinal study, 101 infants who had a familial risk for ASD were enrolled (62% males). Participants completed magnetic resonance imaging scans at 4 or 6 months of age. Subcortical volumes (thalamus, hippocampus, amygdala, basal ganglia, ventral diencephalon, and cerebellum) were automatically extracted. Early gaze and JA behaviors were assessed with standardized measures. The majority of infants were IJA nonresponders (n = 93, 92%), and over half were RJA nonresponders (n = 50, 52%). In the nonresponder groups, models testing the association of subcortical volumes with later ASD diagnosis accounted for age, sex, and cerebral volumes. In the nonresponder IJA group, using regression method, the left hippocampus (B = -0.009, aOR = 0.991, P = 0.025), the right thalamus (B = -0.016, aOR = 0.984, P = 0.026), as well as the left thalamus (B = 0.015, aOR = 1.015, P = 0.019), predicted later ASD diagnosis. Alterations in thalamic and hippocampal macrostructure in at-risk infants who do not engage in IJA may reflect an enhanced vulnerability and may be the key predictors of later ASD development.