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. 2017 May 23;7(1):2258.
doi: 10.1038/s41598-017-02267-1.

Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis

Tatsuya Nagai  1   2 , Kenji Kirihara  2 , Mariko Tada  2 , Daisuke Koshiyama  2 , Shinsuke Koike  3 , Motomu Suga  4 , Tsuyoshi Araki  5 , Kenji Hashimoto  6 , Kiyoto Kasai  7
Affiliations

Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis

Tatsuya Nagai et al. Sci Rep. .

Abstract

Reduced amplitude of mismatch negativity (MMN) is one of the more promising biological markers of schizophrenia. This finding holds true in both early and chronic phases of the disorder, and is compatible with the glutamatergic dysfunction hypothesis. To further establish MMN as a biomarker of aberrant glutamatergic neurotransmission, an exploration for an association with blood levels of glutamatergic amino acids is an important next step. Despite a large body of work investigating MMN in schizophrenia, no previous studies have undertaken this endeavor. Nineteen patients with first-episode psychosis (FEP), 21 ultra-high risk individuals (UHR), and 16 healthy controls (HC) participated in the study. The MMNs in response to duration change (dMMN) and frequency change (fMMN) were measured. The fasting plasma levels of glutamate, glutamine, glycine, D-serine, and L-serine were measured. dMMN amplitudes were significantly reduced in FEP and UHR, compared to HC. The plasma levels of glutamate of FEP were significantly higher than those of HC. Higher plasma levels of glutamate were associated with smaller dMMN amplitudes in the FEP and HC groups. These findings are compatible with the hypothesis that MMN is a useful biological marker of aberrant glutamatergic neurotransmission in the early stages of schizophrenia.

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Conflict of interest statement

T.A. is affiliated with the Department of Youth Mental Health, which is an endowment department supported by an unrestricted grant from Otsuka Pharmaceutical Co., Ltd. The other authors reported no biomedical financial interests or potential conflicts of interest related to the study.

Figures

Figure 1
Figure 1
Grand average waveforms of duration mismatch negativity (dMMN) (left) and frequency mismatch negativity (fMMN) (right) at the electrode FCz in first-episode psychosis (FEP; red line), ultra-high risk (UHR; blue line), and healthy controls (HC; black line).
Figure 2
Figure 2
The plasma levels of glutamate in first-episode psychosis (FEP), ultra-high risk (UHR), and healthy controls (HC).
Figure 3
Figure 3
Correlations between duration mismatch negativity (dMMN) amplitude and the plasma level of glutamate at the electrode FCz in first-episode psychosis (FEP; left), ultra-high risk (UHR; middle), and healthy controls (HC; right).
See this image and copyright information in PMC

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