Heterogeneity of cognitive impairments in patients with first-episode schizophrenia.

Abstract

First-episode schizophrenia (FES) presents with substantial heterogeneity in cognitive performance, yet this variability is frequently overlooked in studies investigating disease pathology and treatment. This study aimed to quantify cognitive heterogeneity across domains and individuals, and to identify distinct cognitive subtypes in FES. We assessed cognitive performance using the MATRICS Consensus Cognitive Battery (MCCB) and clinical symptoms with the Positive and Negative Syndrome Scale (PANSS) in 271 patients with FES and 133 healthy controls (HC). Domain-specific impairment was quantified using Hedges' g, whereas quantile-based analyses were performed to characterize distributional heterogeneity in overall cognitive performance. Gaussian mixture clustering was subsequently applied to identify latent subtypes within FES group. Compared with HC, patients with FES demonstrated significant impairments across all assessed cognitive measures. However, the magnitude of impairment varied across measures, with Attention/Vigilance as the domain with the greatest impairment. Quantile-based analyses demonstrated that the FES-HC difference was significantly greater at the lower than at the upper end of the cognitive distribution, indicating that cognitive impairment was not uniformly distributed across patients. Clustering analysis identified two cognitive subtypes: one subgroup with severe global cognitive deficits and another with relatively preserved cognitive functioning. Crucially, these subtypes also differed significantly in their clinical symptom profiles. In conclusion, specific cognitive impairments may reflect the underlying pathology of early schizophrenia, and individuals can be reliably stratified into distinct cognitive phenotypes. These findings provide critical clinical insights that can directly inform targeted, stratified strategies in early psychosis from a cognitive perspective.