- OBJECTIVE: Schizophrenia is a severe mental disorder associated with nerobiological deficits. Auditory oddball P300 have been found to be one of the most consistent markers of schizophrenia. The goal of this study is to find quantitative features that can objectively distinguish patients with schizophrenia (SCZs) from healthy controls (HCs) based on their recorded auditory odd-ball P300 electroencephalogram (EEG) data. METHODS: Using EEG dataset, we develop a machine learning (ML) algorithm to distinguish 57 SCZs from 66 HCs. The proposed ML algorithm has three steps. In the first step, a brain source localization (BSL) procedure using the linearly constrained minimum variance (LCMV) beamforming approach is employed on EEG signals to extract source waveforms from 30 specified brain regions. In the second step, a method for estimating effective connectivity, referred to as symbolic transfer entropy (STE), is applied to the source waveforms. In the third step the ML algorithm is applied to the STE connectivity matrix to determine whether a set of features can be found that successfully discriminate SCZ from HC. RESULTS: The findings revealed that the SCZs have significantly higher effective connectivity compared to HCs and the selected STE features could achieve an accuracy of 92.68%, with a sensitivity of 92.98% and specificity of 92.42%. CONCLUSION: The findings imply that the extracted features are from the regions that are mainly affected by SCZ and can be used to distinguish SCZs from HCs. SIGNIFICANCE: The proposed ML algorithm may prove to be a promising tool for the clinical diagnosis of schizophrenia.