The 40 Hz auditory steady state response is associated with antipsychotic treatment outcome in acute patients with schizophrenia

ABSTRACT Background Prediction of response to antipsychotic medications remains elusive, and a biomarker assisting in treatment selection would drastically improve prognosis. The 40 Hz auditory steady state response (ASSR) is an EEG biomarker, mirroring the GABA-glutamate signaling and the excitation/inhibition balance, consistently been reported to be impaired in schizophrenia, on, with inconsistent evidence of an association with specific symptoms. Methods N=69 schizophrenia inpatients with an acute psychotic episode underwent an EEG recording to assess event related spectral perturbation (ERSP), intertrial phase coherence (ITC) and phase amplitude coupling (PAC) during the ASSR task, aimed to assess their relationship with response to antipsychotics and with positive, negative, disorganized, excited and depressive symptoms. Moreover, patients were compared with controls (N=36), to delineate schizophrenia acute phase ASSR dynamics. Results Responders to treatment showed a decreased 40 Hz ERSP in both the early (0-0.2s post-stimulus; P=0.0013; d=-0.936) and late (0-2-1.2s post-stimulus; P=0.0022; d=-0.932) time windows compared to non-responders. Using logistic regression and bootstrap optimism correction, ERSP classified the two groups with 70% accuracy. Responders but not non-responders showed a reduced ERSP compared to controls (P=0.0211; d=-0.558). Patients had reduced early ITPC (P=0.0001; d=-1.015) vs controls. responders compared to non-responders had increased PAC in the early (P=0.0215; d00.65) and in patients vs controls, in both the early (P=0.0002; d=0.57) and the late (P=0.0006; d=0.74) windows. No association emerged between ASSR metrics and symptoms severity. Conclusions ASSR is a candidate biomarker for antipsychotic treatment personalization. Only responders to treatment presented a significant gamma-band impairment, in line with previous literature on stabilized outpatients, but not non-responders, indicating that a distinct neurobiology could exist.