2026 ECNP Congress

PS01-1154

Decoding the links between psychosis and autism: neuroanatomical markers of autistic-like symptoms in first-episode psychosis

Betül YILDIRIM — P. Fuentes-Claramonte, R. Salvador, J. Clemente-Calvo, P. Salgado-Pineda, A. Karuk, M.I. Carrión, A. Guerrero-Pedraza, E. Pomarol Clotet, P. Mckenna · FIDMAG Hermanas Hospitalarias Research Foundation, Psychiatry, Barcelona, Spain

2026 ECNP Congress

Background The clinical boundary between schizophrenia and autism spectrum disorder (ASD), previously thought to be absolute, has recently undergone a degree of re-appraisal [1]. Importantly, beyond shared clinical manifestations—such as social withdrawal and repetitive behaviours—evidence suggests significant neurobiological overlap, with evidence of altered brain structure, within the “social brain” and salience networks, particularly volume reductions in the insula [2,3]. Such findings may indicate a common biological basis for the social-cognitive impairments observed across both disorders. Recent research additionally suggests an “autistic phenotype” exists within the schizophrenia spectrum, characterized by severe deficits in communication and social interaction and this can be reliably indexed by scores on a subset of eight items on the PANSS scale [1]. Aim This study aimed to investigate relationships between autistic-like traits, as assessed using the PANSS Autism Severity Score (PAUSS) [1], and brain structure, as measured using whole-brain techniques, in a large sample of non-affective first episode psychosis. Methods This cross-sectional study included 78 patients with non-affective first-episode psychosis (FEP), diagnosed according to DSM-5 criteria via standardized clinical interviews. Clinical symptom severity was evaluated using the Positive and Negative Syndrome Scale (PANSS). To specifically quantify autism-like traits within the sample, we employed the PANSS Autism Severity Score (PAUSS). This composite score was derived from eight specific PANSS items: blunted affect (N1), poor rapport (N3), passive/apathetic social withdrawal (N4), difficulty in abstract thinking (N5), lack of spontaneity and flow of conversation (N6), stereotyped thinking (N7), mannerisms and posturing (G6), and preoccupation (G15).

Neuroimaging was performed using a GE 1.5T scanner to acquire T1-weighted images. Structural MRI data underwent automated pre-processing and cortical reconstruction through the FreeSurfer image analysis suite (http://surfer.nmr.mgh.harvard.edu/). We conducted a whole-brain vertex-wise analysis to investigate the relationship between PAUSS scores and three distinct morphometric parameters: cortical thickness, surface area, and gray matter volume. Age, sex, and estimated premorbid IQ were incorporated as covariates in the statistical models to control for potential confounding effects. For the vertex-wise maps, an initial cluster-forming threshold of p < 0.005 (uncorrected) was applied, followed by rigorous cluster-based correction at p < 0.05 using permutation testing to account for multiple comparisons. Results Total PAUSS scores were significantly and negatively correlated with cortical volume within the right rostral middle frontal gyrus (r-RMFG). These findings demonstrate that more pronounced autistic-like traits are associated with a localized reduction in gray matter volume in this prefrontal area, potentially providing a neuroanatomical explanation for social-cognitive impairments observed during the first-episode of psychosis. Discussion Our findings indicate that in non-affective FEP, autistic-like symptomatology is linked to structural deficits in the right RMFG. This region is a critical hub for high-level social cognition, particularly Theory of Mind (ToM) and mentalizing—the ability to represent the mental states and intentions of others [4, 5]. The observed volume reduction may represent a neurobiological marker of the “autistic phenotype” within the schizophrenia spectrum.

References

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  2. Jutla, A., Foss‐Feig, J., Veenstra‐VanderWeele, J., 2022. Autism spectrum disorder and schizophrenia: An updated conceptual review. Autism Research 15 (3), 384-412.
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