Subgroups of cognitive impairments in schizophrenia characterized by executive function and their morphological features: a latent profile analysis study

Background: The heterogeneity of cognitive impairments in schizophrenia has been widely observed. However, reliable cognitive boundaries to differentiate the subgroups remain elusive. The key challenge for cognitive subtyping is applying an integrated and standardized cognitive assessment and understanding the subgroup-specific neurobiological mechanisms. The present study endeavors to explore cognitive subgroups and identify their morphological features.

Methods: A total of 920 schizophrenia patients and 169 healthy controls were recruited. MATRICS Consensus Cognitive Battery was applied to assess cognitive performance and recognize cognitive subgroups through latent profile and latent transition analysis. Cortical thickness and gray matter volume were employed for the morphological features across subgroups.

Results: Four reproducible cognitive subgroups were identified, including multidomain-intact, executive-preserved, executive-deteriorated, and multidomain-deteriorated subgroup. After 12 weeks of follow-up, the cognitive characteristics of three out of the four subgroups kept stability, except for multidomain-deteriorated subgroup in which 48.8% of patients with improved cognition transited into the executive-deteriorated subgroup. Across subgroups, significant gradient features of brain structure were exhibited in fronto-temporal regions, hippocampus, and insula. Compared to healthy controls, multidomain-intact subgroup showed the most intact cognition and morphology, and multidomain-deteriorated subgroup with youngest age showed morphological decline in extensive regions. The remaining two subgroups showed intermediate cognitive performance, but could be distinguished by executive function and morphological differences in posterior cingulate cortex.

Conclusions: Our study provides novel insights into the heterogeneity of cognitive impairments in schizophrenia and the morphological features from cross-sectional and longitudinal levels, which could advance our understanding of complex cognition-morphology relationships and guide personalized interventions.