• Yuyan Huang, Weiyan Wang, Gangrui Hei, Tiannan Shao, Li Li, Ye Yang, Xiaoyi Wang, Yujun Long, Jingmei Xiao, Xingjie Peng, Chuhan Song, Jingda Cai, Xueqin Song, Xijia Xu, Shuzhan Gao, Jing Huang, Dongyu Kang, Ying Wang, Jingping Zhao, Yunzhi Pan, and Renrong Wu.
• Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
• Bmc Med. 2025 Jan 8; 23 (1): 1313.

BackgroundThe 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.MethodsA 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.ResultsFour 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.ConclusionsOur 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.© 2025. The Author(s).

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