40 Hz Auditory Steady-State Responses Predict Transition to Psychosis in Clinical-High-Risk Participants: A MEG Study

ABSTRACT Objective: To examine whether 40-Hz Auditory Steady-State Responses (ASSR) in participants at clinical high-risk for psychosis predict clinical outcomes. Method: In this study, magnetoencephalography (MEG) data were collected during a 40-Hz ASSR paradigm in 116 participants meeting clinical high-risk (CHR-P) for psychosis criteria, a clinical control group characterized by affective disorders and/or substance abuse (CHR-N: n=38), 32 first-episode psychosis patients (FEP, 14 antipsychotic-naive), and 49 healthy controls. We examined 40-Hz-ASSR- source-activity in bilateral Heschl9s gyrus, superior temporal gyrus, Rolandic operculum, and the thalamus. Group differences in ASSR amplitudes were tested and correlated with neuropsychological scores, psychosocial functioning, and clinical symptoms. Linear discriminant analyses was used to assess whether 40-Hz-ASSR predicts transition to psychosis and persistence of APS. Results: Compared to controls, 40-Hz-ASSR responses in CHR-Ps were impaired in right Rolandic operculum (d=0.41) and right thalamus (d=0.43), particularly in those with combined UHR/BS symptoms and CHR-Ps who transitioned to psychosis (n=11). FEP-patients showed significant impairments in the right thalamus (d=0.58), while the CHR-N group was unaffected. Importantly, right thalamus 40-Hz-ASSRs predicted transition to psychosis (transitioned [n=11] vs non-transitioned [n=105]); classification accuracy 73.3%, AUC=0.827), whereas this was not the case for persistent APS (Persistent [n=41] vs non-Persistent [n=37]; classification accuracy 56.4%). Conclusions: The current study indicates that MEG-recorded 40-Hz-ASSRs constitute a potential biomarker for predicting transition to psychosis in CHR-P participants.