Understanding Depression in Autism: The Role of Subjective Perception and Anterior Cingulate Cortex Volume

Background The prevalence of depression is elevated in individuals with autism spectrum disorder (ASD) compared to the general population, yet the reasons for this disparity remain unclear. While social deficits central to ASD may contribute to depression, it is uncertain whether social interaction behavior themselves or individuals' introspection about their social behaviors are more impactful. Although the anterior cingulate cortex (ACC) and amygdala are frequently implicated in ASD, depression, and social functioning, it is unknown if these regions explain differences between ASD adults with and without co-occurring depression. Methods The present study contrasted observed vs. subjective perception of autism symptoms and social performances assessed with both standardized measures and a lab task, in 65 sex-balanced (52.24% male) autistic young adults. We also quantified ACC and amygdala volume with 7-Tesla structural neuroimaging to examine correlations with depression and social functioning. Results We found that ASD individuals with depression exhibited differences in subjective evaluations including heightened self-awareness of ASD symptoms, lower subjective satisfaction with social relations, and less perceived affiliation during the social interaction task, yet no differences in corresponding observed measures, compared to those without depression. Larger ACC volume was related to depression, greater self-awareness of ASD symptoms, and worse subjective satisfaction with social interactions. In contrast, amygdala volume, despite its association with clinician-rated ASD symptoms, was not related to depression. Limitations : Due to the cross-sectional nature of our study, we cannot determine the directionality of the observed relationships. Additionally, we included only individuals with an IQ over 60 to ensure participants could complete the social task, which excluded many on the autism spectrum. We also utilized self-reported depression indices instead of clinically diagnosed depression, which may limit the comprehensiveness of the findings. Conclusions Our approach highlights the unique role of subjective perception of autism symptoms and social interactions, beyond the observable manifestation of social interaction in ASD, in contributing to depression, with the ACC playing a crucial role. These findings imply possible heterogeneity of ASD concerning co-occurring depression. Using neuroimaging, we were able to demarcate depressive phenotypes co-occurring alongside autistic phenotypes.