A potential mechanistic role for neuroinflammation in reward processing impairments in autism spectrum disorder

Abstract

Accumulating evidence suggests that autism spectrum disorder (ASD) may be conceptualized within a framework of reward processing impairments. The Social Motivation Theory of Autism posits that reduced motivation to interact with people and decreased pleasure derived from social interactions may derail typical social development and contribute to the emergence of core social communication deficits in ASD. Neuroinflammation may disrupt the development of mesolimbic dopaminergic systems that are critical for optimal functioning of social reward processing systems. This neuroinflammation-induced disturbance of mesolimbic dopaminergic functioning has been substantiated using maternal immune activation rodent models whose offspring show aberrant dopaminergic corticostriatal function, as well as behavioral characteristics of ASD model systems. Preclinical findings are in turn supported by clinical evidence of increased mesolimbic neuroinflammatory responses in individuals with ASD. This review summarizes evidence for reward processing deficits and neuroinflammatory impairments in ASD and examines how immune inflammatory dysregulation may impair the development of dopaminergic mesolimbic circuitry in ASD. Finally, future research directions examining neuroinflammatory effects on reward processing in ASD are proposed.