Gamma and theta band auditory steady-state responses in acute patients with schizophrenia and their association with antipsychotic treatment outcome

Few schizophrenia EEG studies were realized during acute psychotic episodes, which represent a favorable vantage point to assess pathophysiology and to establish predictive biomarkers of response to antipsychotic medications. The EEG 40 Hz auditory steady state response (ASSR) reflects the GABA-glutamate signaling and the excitation/inhibition imbalance and is impaired in schizophrenia. High-density EEG was recorded in acute inpatients with schizophrenia (N = 91) and healthy controls (N = 45) to assess the ASSR metrics event related spectral perturbation (ERSP) and intertrial phase coherence (ITC), in both gamma (38–42 Hz) and theta (4–8 Hz) bands. Furthermore, we investigated the relationship of these parameters with response to antipsychotics and with positive, negative, disorganized, excited and depressive symptoms. No ERSP and ITC differences emerged in gamma band between patients and controls. Patients showed reduced theta ITC in both the early (0-0.25s post-stimulus; d=-0.97; p = < .001) and the late (0.25-1.25s post-stimulus; p = 0.024, d=-0.62) time windows compared to controls, and a similar reduction in ERSP (early: d=-0.88; P = < .001; late: d=-0.64; p = 0.013). Responders to treatment showed reduced gamma ITC (early: d=-0.64, P = 0.015; late: d=-0.62, p = 0.025) and late ERSP (d=-0.57, p = 0.025) compared to non-responders. Non-responders showed increased gamma ITC (early: d = 0.65, p = 0.002; late: d = 0.61, p = 0.010) and ERSP (early: d = 0.57, p = 0.024; late: d = 0.67, p = 0.005) compared to controls. In conclusion, patients with schizophrenia having an acute psychotic episode display unexpected ASSR responses, with reduced theta ITC and ERSP, and no reduction in gamma activity. An increased gamma band activity characterizes the neurobiology of non-responders to antipsychotics, representing a candidate biomarker for treatment outcome stratification.