# Illness Severity in Psychotic Disorders Amplifies Anterior Insula’s Sensitivity to Unreciprocated Smiles

**Authors:** Jayson Jeganathan, Megan E. J. Campbell, Renate Thienel, Nikitas C. Koussis, Bryan Paton, Katharina V. Wellstein, Michael Breakspear

PMC · DOI: 10.5334/cpsy.142 · Computational Psychiatry · 2025-12-30

## TL;DR

Severe psychotic disorders increase brain sensitivity to unreciprocated smiles, potentially explaining social smiling impairments.

## Contribution

The study identifies the anterior insula's role in processing unreciprocated smiles and its amplification in severe illness.

## Key findings

- Greater illness severity correlates with reduced smile amplitude and heightened anterior insula activation.
- Incongruent facial reactions activate the anterior insula and supplementary motor cortex more in clinical participants.
- Dynamic causal modeling shows reduced self-inhibition in the anterior insula due to incongruent stimuli.

## Abstract

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.

## Linked entities

- **Diseases:** schizophrenia (MONDO:0005090), schizoaffective disorder (MONDO:0005487)

## Full-text entities

- **Diseases:** schizophrenia (MESH:D012559), Psychotic Disorders (MESH:D011618)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12758102/full.md

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Source: https://tomesphere.com/paper/PMC12758102