Illness Severity in Psychotic Disorders Amplifies Anterior Insula's Sensitivity to Unreciprocated Smiles.

When we smile, we expect that others will smile back. When one's smile is not reciprocated, these expectations are violated, producing prediction error signals in the brain. Prediction error signals may be experienced as aversive, disincentivizing smiling. Social smiling is impaired in psychotic disorders suggesting increased sensitivity to unreciprocated smiles. We developed the Incongruent Facial Emotion task to probe responses to unreciprocated smiles. Healthy controls and persons with schizophrenia or schizoaffective disorder voluntarily smiled, after which they viewed a stimulus face with a happy or angry expression. Brain activations were quantified with functional magnetic resonance imaging. Greater illness severity was associated with reduced smile amplitude. Across both groups, viewing an incongruent stimulus after initiating a smile activated the bilateral anterior insulae and right supplementary motor cortex. Brain activations in the left middle occipital and left superior frontal gyri were greater in the clinical group. The anterior insula response to incongruent facial reactions was significantly greater in more severely ill clinical participants. Dynamic causal modelling suggests that incongruent stimuli reduce tonic self-inhibition in the anterior insula, and that this disinhibition is enhanced by illness severity. The results suggest that the anterior insula processes affective prediction errors and sends feedback to supplementary motor areas to alter behavioural responses. The underlying brain circuits are enhanced in clinical participants with severe illness, suggesting new avenues to understand affective blunting in psychotic disorders.