Clustering of Cognitive Subtypes in Schizophrenia Patients and Their Siblings: Relationship with Regional Brain Volumes

Schizophrenia patients (SZH) often show impaired cognition and reduced brain structural volumes; these deficits are also detectable in healthy relatives of SZH. However, there is considerable heterogeneity: a sizable percentage of SZH are relatively cognitively intact; clustering strategies have proved useful for categorising into cognitive subgroups. We used a clustering strategy to investigate relationships between subgroup assignment and brain volumes, in 102 SZH (N = 102) and 32 siblings of SZH (SZH-SIB), alongside 92 controls (CON) and 48 of their siblings. SZH had poorer performance in all cognitive domains, and smaller brain volumes within prefrontal and temporal regions compared to controls. We identified three distinct cognitive clusters (‘neuropsychologically normal’, ‘intermediate’, ‘cognitively impaired’) based on age- and gender-adjusted cognitive domain scores. The majority of SZH (60.8%) were assigned to the cognitively impaired cluster, while the majority of SZH-SIB (65.6%) were placed in the intermediate cluster. Greater right middle temporal volume distinguished the normal cluster from the more impaired clusters. Importantly, the observed brain volume differences between SZH and controls disappeared after adjustment for cluster assignment. This suggests an intimate link between cognitive performance levels and regional brain volume differences in SZH. This highlights the importance of accounting for heterogeneity in cognitive performance within SZH populations when attempting to characterise the brain structural abnormalities associated with the disease.