Face Emotion Processing in Pediatric Irritability: Neural Mechanisms in a Sample Enriched for Irritability With Autism Spectrum Disorder

Abstract Objective Characterizing the pathophysiology of irritability symptoms from a dimensional perspective above and beyond diagnostic boundaries is key to developing mechanism-based interventions that can be applied broadly. Face emotion processing deficits are present in youths with elevated levels of irritability. The present study aimed to identify the neural mechanisms of face emotion processing, in a sample enriched for irritability by including youth with high functioning autism spectrum disorder (HF-ASD). Method Youths (N=120, age=8.3-19.2 years) completed an implicit face emotion task during fMRI acquisition. We evaluated how irritability, measured dimensionally, above and beyond diagnostic group, relates to whole-brain neural activation and amygdala connectivity in response to face emotions. Results Both neural activation and amygdala connectivity differed as a function of irritability level and face emotion in the prefrontal cortex. Youths with higher irritability levels had decreased activation in response to both fearful and happy faces in the left middle frontal gyrus and to happy faces in the left inferior frontal gyrus. Furthermore, increased irritability levels were associated with altered right amygdala connectivity to the left superior frontal gyrus when viewing fearful and sad faces. Conclusion The neural mechanisms of face emotion processing differ in youths with higher irritability compared to their less irritable peers. The findings suggest that these irritability mechanisms may be common to both typically developing and HF-ASD youths. Understanding the neural mechanisms of pediatric irritability symptoms that cut across diagnostic boundaries may be leveraged for future intervention development.