A Machine Learning Approach Using Effective Connectivity to Predict Response to Clozapine Treatment

Abstract

Clozapine is an anti-psychotic drug that is known to be effective in the treatment of patients with chronic treatment-resistant schizophrenia (TRS-SCZ), commonly estimated to be around one third of all cases. However, clinicians sometimes delay the initiation of this drug because of its adverse side-effects. Therefore, identification of predictive biological markers of clozapine response are extremely valuable to aid on-time initiation of treatment. In this study, we develop a machine learning (ML) algorithm based on pre-treatment electroencephalogram (EEG) data sets to predict response to clozapine treatment in 57 TRS-SCZs, where the treatment outcome, after at least one-year follow-up is determined using the positive and negative syndrome scale (PANSS). The ML algorithm has three steps: 1) a brain source localization (BSL) procedure using the linearly constrained minimum variance (LCMV) beamforming approach is employed on the EEG signals to extract source waveforms from 30 specified brain regions. 2) An effective connectivity measure named symbolic transfer entropy (STE) is applied to the source waveforms. 3) A ML algorithm is applied to the STE matrix to determine whether a set of features can be found to discriminate most-responder (MR) SCZ patients from least-responder (LR) ones. The findings of this study reveal that STE features can achieve an accuracy of 95.83%. This finding implies that analysis of pre-treatment EEG could contribute to our ability to distinguish MR from LR SCZs, and that the source STE matrix may prove to be a promising tool for the prediction of the clinical response to clozapine.