Treatment response prediction and individualized identification of first-episode drug-naive schizophrenia using brain functional connectivity

Identifying biomarkers in schizophrenia during the first episode without the confounding effects of treatment has been challenging. Leveraging these biomarkers to establish diagnosis and make individualized predictions of future treatment responses to antipsychotics would be of great value, but there has been limited progress. In this study, by using machine learning algorithms and the functional connections of the superior temporal cortex, we successfully identified the first-episode drug-naive (FEDN) schizophrenia patients (accuracy 78.6%) and predict their responses to antipsychotic treatment (accuracy 82.5%) at an individual level. The functional connections (FC) were derived using the mutual information and the correlations, between the blood-oxygen-level dependent signals of the superior temporal cortex and other cortical regions acquired with the resting-state functional magnetic resonance imaging. We also found that the mutual information and correlation FC was informative in identifying individual FEDN schizophrenia and prediction of treatment response, respectively. The methods and findings in this paper could provide a critical step toward individualized identification and treatment response prediction in first-episode drug-naive schizophrenia, which could complement other biomarkers in the development of precision medicine approaches for this severe mental disorder.