Fear Potentiated Startle in Children With Autism Spectrum Disorder: Association With Anxiety Symptoms and Amygdala Volume

Atypical responses to fearful stimuli and the presence of various forms of anxiety are commonly seen in children with autism spectrum disorder (ASD). The fear potentiated startle paradigm (FPS), which has been studied both in relation to anxiety and as a probe for amygdala function, was carried out in 97 children aged 9-14 years including 48 (12 female) with ASD and 49 (14 female) with typical development (TD). In addition, exploratory analyses were conducted examining the association between FPS and amygdala volume as assessed with magnetic resonance imaging in a subset of the children with ASD with or without an anxiety disorder with available MRI data. While the startle latency was increased in the children with ASD, there was no group difference in FPS. FPS was not significantly associated with traditional Diagnostic and Statistical Manual (DSM) or "autism distinct" forms of anxiety. Within the autism group, FPS was negatively correlated with amygdala volume. Multiple regression analyses revealed that the association between FPS and anxiety severity was significantly moderated by the size of the amygdala, such that the association between FPS and anxiety was significantly more positive in children with larger amygdalas than smaller amygdalas. These findings highlight the heterogeneity of emotional reactivity associated with ASD and the difficulties in establishing biologically meaningful probes of altered brain function. LAY SUMMARY: Many children with autism spectrum disorder (ASD) have additional problems such as anxiety that can greatly impact their lives. How these co-occurring symptoms develop is not well understood. We studied the amygdala, a region of the brain critical for processing fear and a laboratory method called fear potentiated startle for measuring fear conditioning, in children with ASD (with and without an anxiety disorder) and typically developing children. Results showed that the connection between fear conditioning and anxiety is dependent on the size of the amygdala in children with ASD.