Identification of two clusters within schizophrenia with different structural, functional and clinical characteristics

Background: Several biologically distinct subgroups may coexist within schizophrenia, which may hamper the necessary replicability to translate research findings into clinical practice. Methods: Cortical thickness, curvature and area values and subcortical volumes of 203 subjects (121 schizophrenia patients, out of which 64 were first episodes), 60 healthy controls and 22 bipolar patients were used to identify clusters using principal components and canonical discriminant analyses. Regional glucose metabolism using positron emission tomography, P300 event related potential, baseline clinical data and percentage of improvement with treatment were used to validate possible clusters based on MRI data. Results: All the controls, the bipolar patients and most of the schizophrenia patients were grouped in a cluster (cluster A). A group of 24 schizophrenia patients (12 first episodes), characterized by large intrinsic curvature values, was identified (cluster B). These patients, but not those in cluster A, showed reduced thalamic and cingulate glucose metabolism in comparison to controls, as well as a worsening of negative symptoms at follow-up. Patients in cluster A showed a significant putaminal metabolic increase, which was not observed for those in cluster B. P300 amplitude was reduced in patients of both clusters, in comparison to controls. Conclusions: Results of this study support the existence of a biologically distinct group within the schizophrenia syndrome, characterized by increased cortical curvature values, reduced thalamic and cingulate metabolism, lack of the expected increased putaminal metabolism with antipsychotics and persistent negative symptoms.