40 Hz Auditory Steady State Responses in Schizophrenia: Towards 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. In the current paper, 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/inhibition. We will then summarize findings from electro- and magnetoencephalographical studies in clinical high-risk for psychosis participants, first-episode psychosis and schizophrenia patients to identify the pattern of deficits across illness-stages, the relationship with clinical variables and 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 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.