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Sensory impairments constitute core dysfunctions in schizophrenia. In the auditory modality, impaired mismatch negativity (MMN) has been observed in chronic schizophrenia and may reflect N-methyl-d-aspartate (NMDA) hypo-function, consistent with models of schizophrenia based on oxidative stress. Moreover, a recent study demonstrated deficits in the N100 component of the auditory evoked potential (AEP) in early psychosis patients. Previous work has shown that add-on administration of the glutathione precursor N-acetyl-cysteine (NAC) improves the MMN and clinical symptoms in chronic schizophrenia. To date, it remains unknown whether NAC also improves general low-level auditory processing and if its efficacy would extend to early-phase psychosis. We addressed these issues with a randomized, double-blind study of a small sample (N=15) of early psychosis (EP) patients and 18 healthy controls from whom AEPs were recorded during an active, auditory oddball task. Patients were recorded twice: once prior to NAC/placebo administration and once after six months of treatment. The N100 component was significantly smaller in patients before NAC administration versus controls. Critically, NAC administration improved this AEP deficit. Source estimations revealed increased activity in the left temporo-parietal lobe in patients after NAC administration. Overall, the data from this pilot study, which call for replication in a larger sample, indicate that NAC improves low-level auditory processing in early psychosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Patients diagnosed with schizophrenia often present with low-level sensory deficits. It is an open question whether there is a functional link between these deficits and the pathophysiology of the disease, e.g. oxidative stress and glutathione (GSH) metabolism dysregulation. Auditory evoked potentials (AEPs) were recorded from 21 psychosis disorder patients and 30 healthy controls performing an active, auditory oddball task. AEPs to standard sounds were analyzed within an electrical neuroimaging framework. A peripheral measure of participants' redox balance, the ratio of glutathione peroxidase and glutathione reductase activities (GPx/GR), was correlated with the AEP data. Patients displayed significantly decreased AEPs over the time window of the P50/N100 complex resulting from significantly weaker responses in the left temporo-parietal lobe. The GPx/GR ratio significantly correlated with patients' brain activity during the time window of the P50/N100 in the medial frontal lobe. We show for the first time a direct coupling between electrophysiological indices of AEPs and peripheral redox dysregulation in psychosis patients. This coupling is limited to stages of auditory processing that are impaired relative to healthy controls and suggests a link between biochemical and sensory dysfunction. The data highlight the potential of low-level sensory processing as a trait-marker of psychosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)