Daisuke Koshiyama 1 , Kenji Kirihara 1 , Mariko Tada 1 , 2 , Tatsuya Nagai 1 , 3 , Mao Fujioka 1 , Eriko Ichikawa 1 , Kazusa Ohta 1 , Motoko Tani 1 , Maiko Tsuchiya 1 , Akiko Kanehara 1 , Kentaro Morita 1 , Kingo Sawada 1 , Jun Matsuoka 1 , Yoshihiro Satomura 1 , Shinsuke Koike 1 , 2 , 4 , 5 , Motomu Suga 1 , 6 , Tsuyoshi Araki 1 , Kiyoto Kasai , 1 , 2
8 October 2018
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.