Linking biochemistry, brain & behavior through allostasis of the amygdala in autism

Autism is a syndrome of social impairment, commonly attributed to an inability to process socially relevant stimuli. This theory derives mainly from tasks involving emotional facial expressions, but autistic individuals tend not to look at eye regions, potentially confounding these results. Recent work from our laboratory employed automated eye-tracking and functional MRI to reveal that relevant brain regions like the fusiform "face area" are in fact activated when autistic individuals look at the eyes of faces. The amygdala, a center of emotional arousal and fear, is actually over-responsive when autistics look at eye regions. This suggests that autism may be a disorder not of social oblivion but of hypersensitivity to and avoidance of social stimuli. The following dissertation studies were designed to test for structural and neurochemical evidence of chronic amygdala overload in autism.;Amygdala volume has been heavily studied in autism, but wildly inconsistent findings have cast doubt on a role for amygdala neuropathology in autism. We discovered the first relationship between amygdala volume and severity of current and early childhood autistic social impairments. Autistic severity showed an interaction with age, suggesting that amygdala volume follows a different trajectory in more severely impaired individuals. This led us to apply results from animal models of chronic overload or "allostasis" to autism and we found this could resolve all of the discrepancies in the existing literature. We also aimed to understand amygdala neurochemistry, including the major neurotransmitters glutamate and GABA. We developed an amygdala-specific magnetic resonance spectroscopy procedure and demonstrated the feasibility of measuring individual differences in amygdala neurochemistry. Importantly, reliable estimates of neurotransmitters required novel considerations of age and time of day. Finally, we characterize amygdala neurochemistry, including excitation-inhibition ratio, and longitudinal change in amygdala volume in a sample of autistic and control adolescents and adults. Our findings support a hypothesis of chronic overload in the autistic amygdala.