Up to 40% of youth with autism spectrum disorder (ASD) also suffer from
anxiety, and this comorbidity is linked with significant functional
impairment. However, the mechanisms of this overlap are poorly understood. We
investigated the interplay between ASD traits and anxiety during reward
processing, known to be affected in ASD, in a community sample of 1472
adolescents (mean age=14.4 years) who performed a modified monetary incentive
delay task as part of the Imagen project. Blood-oxygen-level dependent (BOLD)
responses to reward anticipation and feedback were compared using a 2x2
analysis of variance test (ASD traits: low/high; anxiety symptoms: low/high),
controlling for plausible covariates. In addition, we used a longitudinal
design to assess whether neural responses during reward processing predicted
anxiety at 2-year follow-up. High ASD traits were associated with reduced BOLD
responses in dorsal prefrontal regions during reward anticipation and negative
feedback. Participants with high anxiety symptoms showed increased lateral
prefrontal responses during anticipation, but decreased responses following
feedback. Interaction effects revealed that youth with combined ASD traits and
anxiety, relative to other youth, showed high right insula activation when
anticipating reward, and low right-sided caudate, putamen, medial and lateral
prefrontal activations during negative feedback (all clusters PFWE<0.05). BOLD
activation patterns in the right dorsal cingulate and right medial frontal
gyrus predicted new-onset anxiety in participants with high but not low ASD
traits. Our results reveal both quantitatively enhanced and qualitatively
distinct neural correlates underlying the comorbidity between ASD traits and
anxiety. Specific neural responses during reward processing may represent a
risk factor for developing anxiety in ASD youth