18-kDa Translocator Protein Signaling and Reward Circuitry Functioning in Autism Spectrum Disorder

The Social Motivation Hypothesis of Autism highlights disruptions in brain systems that process rewards as a factor that contributes to autism pathophysiology. In autism spectrum disorder (ASD), impairments in social communication have also been associated with elevated inflammatory profiles and atypical neural responses to social reward. These findings have led to theories hypothesizing that immune dysfunction is an underlying mechanism of social impairments and ASD etiology. In the present study, we aimed to further clarify and unify these theories by examining simultaneous positron emission tomography magnetic resonance (PET-MR) imaging using the radioligand [18F]PBR111 to assess 18-kDa translocator protein (TSPO) expression and symptom data from young adults with and without ASD to examine the impact of immune functioning on neural response to reward and ASD symptom severity. There were no differences between the ASD and comparison groups in TSPO expression, an index of immune functioning. However, TSPO expression in several brain regions was associated with ASD symptom severity. This work provides evidence of associations between neuroimmune and social functioning in ASD, presenting a valuable opportunity for future treatment research. This is also the first study to examine how immune functioning (TSPO PET) impacts ASD symptom severity through disruptions in reward responsivity.