Beyond severity: Characterizing cognitive heterogeneity in schizophrenia at the level of cognitive structure

Cognitive heterogeneity is a fundamental feature of schizophrenia (SCZ), but conventional domain-based scoring approaches reduce cognition to single values, overlooking its underlying structure and primarily reflecting the severity of cognitive impairment rather than qualitative differences. To address this gap, this study derived and validated a normative latent cognitive structure (N-LCS) as a reference for evaluating individual cognition relative to the norm, providing a basis for characterizing cognitive heterogeneity in SCZ. The N-LCS was reproducible across cohorts, whereas only moderate structural similarity was observed between different cognitive batteries. In the present cohorts, N-LCS deviation metrics were associated with negative symptoms, which were not fully captured by score-based methods. Heterogeneous changes in cognitive structure emerge at the unaffected sibling stage as indicated by N-LCS, preceding both clinical onset and measurable score-level differences. Cognitive heterogeneity in SCZ can be characterized along three N-LCS-derived dimensions, providing both quantitative and qualitative delineation. It also mitigates limitations of conventional domain labels that may lead clinically distinct patients to be regarded as cognitively similar. The N-LCS may complement routine neuropsychological assessment by incorporating additional structure-level information and may help guide clinical considerations for specific interventions.