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

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.