Cognitive subgroups of affective and non-affective psychosis show differences in medication and cortico-subcortical brain networks

Cognitive deficits are prevalent in individuals with psychosis and are associated with neurobiological changes, potentially serving as an endophenotype for psychosis. Using the HCP-Early-Psychosis-dataset (n = 226), we aimed to investigate cognitive subtypes (deficit/intermediate/spared) through data-driven clustering in affective (AP) and non-affective psychosis patients (NAP) and controls (HC). We explored differences between three clusters in symptoms, cognition, medication, and grey matter volume. Applying principal component analysis, we selected features for clustering. Features that explained most variance were scores for intelligence, verbal recognition and comprehension, auditory attention, working memory, reasoning and executive functioning. Fuzzy K-Means clustering on those features revealed that the subgroups significantly varied in cognitive impairment, clinical symptoms, and, importantly, also in medication and grey matter volume in fronto-parietal and subcortical networks. The spared cluster (86%HC, 37%AP, 17%NAP) exhibited unimpaired cognition, lowest symptoms/medication, and grey matter comparable to controls. The deficit cluster (4%HC, 10%AP, 47%NAP) had impairments across all domains, highest symptoms scores/medication dosage, and pronounced grey matter alterations. The intermediate deficit cluster (11%HC, 54%AP, 36%NAP) showed fewer deficits than the second cluster, but similar symptoms/medication/grey matter to the spared cluster. Controlling for medication, cognitive scores correlated with grey matter changes and negative symptoms across all patients. Our findings generally emphasize the interplay between cognition, brain structure, symptoms, and medication in AP and NAP, and specifically suggest a possible mediating role of cognition, highlighting the potential of screening cognitive changes to aid tailoring treatments and interventions.