Electrophysiological intermediate biomarkers for oxidative stress in schizophrenia

Objective: Diverse electrophysiological abnormalities have been associated with schizophrenia, but the underlying causes remain elusive. We tested whether the altered oxidative stress in schizophrenia contributes to the electrophysiological abnormalities.

Methods: We used an auditory oddball task to measure mismatch negativity (MMN) and gamma band response on 29 schizophrenia patients and 25 normal controls. Oxidative stress was assessed by monomeric glutathione (GSH, reduced form) and glutathione disulfide (GSSG, oxidized form).

Results: Patients had reduced MMN (p=0.015) and reduced power of gamma band responses at 21-40 Hz and 41-85 Hz (all p<0.001). GSH was significantly lower (p<0.001) while %GSSG was higher (p=0.023) in patients compared with controls. MMN was correlated with GSH in controls; while 21-40 Hz responses were correlated with GSH in patients. Lower GSH and higher GSSG levels were associated with low community functioning (p=0.018). Multivariate mediation modeling showed that gamma band at 21-40 Hz was a significant mediator for GSH effect on community functions.

Conclusions: High beta/low gamma range (21-40 Hz) responses may be an intermediate biomarker indexing oxidative stress and its effect on clinical functions.

Significance: Electrophysiological abnormalities and associated clinical functional changes may in part be associated with heightened oxidative stress in schizophrenia.