Distinct neuroanatomic subtypes in antipsychotic-treated patients with schizophrenia classified by the predefined classification in a never-treated sample.

Background: Distinct neuroanatomic subtypes have been identified in never-treated patients with schizophrenia based on cerebral structural abnormalities, but whether antipsychotic-treated patients would be stratified under the guidance of such previously formed classification remains unclear.

Objective: The present study aimed to investigate alterations of brain structures in antipsychotic-treated patients with schizophrenia based on a predefined morphological classification and their relationships with cognitive performance.

Methods: Cortical thickness, surface area, and subcortical volume were extracted from 147 antipsychotic-treated patients with schizophrenia using structural magnetic resonance imaging for classification. The Brief Assessment of Cognition in Schizophrenia (BACS) and Positive and Negative Syndrome Scale (PANSS) were used to assess cognition and symptoms.

Results: Antipsychotic-treated patients were categorized into three subtypes with distinct patterns of brain morphological alterations. Subtypes 1 and 2 were characterized by widespread deficits in cortical thickness but relatively limited deficits in surface area. In contrast, subtype 3 demonstrated cortical thickening mainly in parietal-occipital regions and widespread deficits in surface area. All three subgroups demonstrated cognitive deficits compared with healthy controls. Significant associations between neuroanatomic and cognitive abnormalities were only observed in subtype 1, where cortical thinning in the left lingual gyrus was conversely related to symbol coding performance.

Conclusions: Similar to drug-naïve patients, neuroanatomic heterogeneity exists in antipsychotic-treated patients, with disparate associations with cognition. These findings promote our understanding of relationships between neuroanatomic abnormalities and cognitive performance in the context of heterogeneity. Moreover, these results suggest that neurobiological heterogeneity needs to be considered in cognitive research in schizophrenia.