40-Hz Auditory Steady-State Responses in Schizophrenia: Toward a Mechanistic Biomarker for Circuit Dysfunctions and Early Detection and Diagnosis

There is converging evidence that 40-Hz auditory steady-state responses (ASSRs) are robustly impaired in schizophrenia and could constitute a potential biomarker for characterizing circuit dysfunctions as well as enable early detection and diagnosis. Here, we provide an overview of the mechanisms involved in 40-Hz ASSRs, drawing on computational, physiological, and pharmacological data with a focus on parameters modulating the balance between excitation and inhibition. We will then summarize findings from electro- and magnetoencephalographic studies in participants at clinical high risk for psychosis, patients with first-episode psychosis, and patients with schizophrenia to identify the pattern of deficits across illness stages, the relationship with clinical variables, and the prognostic potential. Finally, data on genetics and developmental modifications will be reviewed, highlighting the importance of late modifications of 40-Hz ASSRs during adolescence, which are closely related to the underlying changes in GABA (gamma-aminobutyric acid) interneurons. Together, our review suggests that 40-Hz ASSRs may constitute an informative electrophysiological approach to characterize circuit dysfunctions in psychosis that could be relevant for the development of mechanistic biomarkers.