Electrophysiological evidence for abnormal glutamate-GABA association following psychosis onset

摘要

Previous studies have shown glutamatergic dysfunction and γ-aminobutyric acid (GABA)-ergic dysfunction in schizophrenia. Animal studies suggest that N-methyl-d-aspartate receptor (NMDAR) dysfunction and GABA-ergic dysfunction interact with each other and lead to alterations in excitatory/inhibitory balance. The NMDAR and GABAergic-interneuron functions may be indexed by mismatch negativity (MMN) and auditory steady-state gamma-band response (ASSR), respectively. However, no previous studies have tested the hypothesis of an abnormal association between MMN and gamma-band ASSR in the same patients to identify the in vivo evidence of NMDAR-GABA association during the early stages of psychosis. Participants were individuals with recent-onset schizophrenia (ROSZ; N?=?21), ultra-high risk (UHR; N?=?27), and healthy controls (HCs; N?=?24). The MMN amplitude was significantly impaired in ROSZ (p?=?0.001, d?=?1.20) and UHR (p?=?0.003, d?=?1.01) compared with HCs. The intertrial phase coherence (ITC) index of gamma-band ASSR was significantly reduced in ROSZ compared with HCs (p??0.001, d?=?–1.27) and UHR (p?=?0.032, d?=?–0.75). The event-related spectral perturbation (ERSP) index of gamma-band ASSR was significantly smaller in ROSZ compared with HCs (p??0.001, d?=??1.21). The MMN amplitude was significantly correlated with the ITC in ROSZ (r?=??0.69, p??0.001). These findings provide the first in vivo evidence that an abnormal association of the electrophysiological indices of NMDAR and GABA dysfunctions may be present in recent-onset schizophrenia.