Beyond severity: Mapping cognitive heterogeneity in schizophrenia at the structural level.

Area of Science:

• Neuroscience
• Psychiatry
• Cognitive Psychology

Background:

• Cognitive heterogeneity is a key characteristic of schizophrenia (SCZ).
• Current methods using domain-specific scores may not fully capture the complex cognitive structure in SCZ.
• A novel approach is needed to better understand cognitive variations in schizophrenia.

Purpose of the Study:

• To develop and validate a norm-anchored cognitive structural deviation (NCSD) framework to analyze cognitive heterogeneity in SCZ.
• To investigate global and structural cognitive deviations in SCZ patients compared to healthy controls (HC).
• To quantify these deviations using novel indices and explore their clinical associations.

Main Methods:

• Developed a norm-anchored latent cognitive structure (N-LCS) derived from healthy controls (HC).
• Applied the NCSD framework to assess cognitive performance in SCZ patients, quantifying global deviation (CNDI) and structural alterations (LPD, CSD).
• Validated the N-LCS in an independent cohort and performed robustness analyses for SCZ-specific findings.

Main Results:

• The N-LCS demonstrated stability and validity in distinguishing cognitive structures.
• SCZ patients exhibited significant global deviation (CNDI) from the N-LCS and altered executive function indicator patterns (LPD).
• Correlation patterns among cognitive measures differed between SCZ and HC (CSD), with LPD and CSD associated with anxiety and positive symptoms.

Conclusions:

• Cognitive heterogeneity in SCZ encompasses both global deviations and alterations in cognitive structure.
• The NCSD framework offers a refined method for characterizing cognitive heterogeneity in SCZ.
• This approach may advance precision psychiatry and strategies for functional recovery in schizophrenia.