Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated withneuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosispatients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitiveperformance and validated the solution independently (N=53). Cognitive subgroups and healthy controls (HC;n=195) wereclassified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N=67) andimpaired (N=41) subgroup were revealed and partially independently validated (Nspared=40,Nimpaired=13). Impaired patientsshowed significantly increased negative symptomatology (pfdr=0.003), reduced cognitive performance (pfdr< 0.001) and generalfunctioning (pfdr< 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in bothdiscovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balancedaccuracy=60.1%,p=0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphologicalchanges in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Ourfindings emphasize therelevance of tailored intervention early in the course of psychosis for patients suffering from the likely strongerneurodevelopmental character of the disease.