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

Nagai, Tatsuo; Kirihara, Kazuhiro; Tada, Mariko; Koshiyama, Daisuke; Koike, Shinsuke; Suga, Moritaka; Araki, Tsuyoshi; Hashimoto, Kenji; Kasai, Kiyoto

doi:10.1038/s41598-017-02267-1

Cited by 43 publications

(44 citation statements)

References 61 publications

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“…Only asparagine level decreased after treatment, but it was still higher compared to control group. Our results supported the previous findings of increased plasma glutamate level in FEP patients (Nagai et al, ). Similarly, a proton magnetic spectroscopy study revealed that glutamate level was increased in the striatum and cerebellum in FEP patients before the treatment (De La Fuente‐Sandoval et al, ).…”

Section: Discussionsupporting

confidence: 94%

“…There are a few numbers of studies investigating blood serine levels in FEP patients compared to ones in schizophrenia patients. Nagai et al () did not show any difference for l ‐serine, d ‐serine, glycine, and glutamine in FEP patients compared to healthy subjects and ultra‐high risk individuals. However, we showed a significant increase in serine and glutamine levels in FEP patients.…”

Section: Discussionmentioning

confidence: 91%

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Alteration in NMDAR‐related amino acids in first episode psychosis

Garip

Kayır

2019

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The aim of the present study was to explore the role of N‐methyl‐D‐aspartate receptor (NMDAR) related amino acids in drug‐naive first episode psychosis (FEP) patients. The medication naïve patients with FEP (n = 40) and healthy volunteers with no family history of schizophrenia (n = 35) were recruited to the study and followed up for 10 weeks. Liquid chromatography–mass spectrometry method was used to measure plasma levels of the amino acids. The plasma glutamine, glutamic acid, proline, serine, asparagine, and hydroxyproline levels were significantly higher in the FEP patients compared to healthy controls (p values < .0001). The glutamine/glutamic acid ratio in FEP patients was not different from the healthy controls (p > .05). After the antipsychotic treatment, plasma glutamic acid, proline, and hydroxyproline levels were significantly increased (p values < .05) while the asparagine level and glutamine/glutamic acid ratio were decreased (p values < .05). The serine and glutamine levels did not show any differences with the treatment (p > .05). The initial plasma glutamine levels were negatively correlated with the initial Scale for the Assessment of Positive Symptoms (SAPS) score (r = −.45, p = .003). The initial plasma proline levels were negatively correlated with the initial and follow‐up SAPS scores (r = −.51 and −.39, p values < .05). The initial plasma proline and hydroxyproline levels were both negatively correlated with the initial Brief Psychiatric Rating Scale score (r = −.37, p = .017 and r = −.33, p = .033, respectively). Increase in NMDAR‐related amino acid levels during the FEP may be a compensatory response to glutamatergic hypofunction. Their plasma levels were significantly correlated with several psychotic symptoms before and after 10‐week treatment. Antipsychotic treatment has differential effects on the plasma levels of these amino acids.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 91%

Alteration in NMDAR‐related amino acids in first episode psychosis

Garip

Kayır

2019

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“…The onset of the auditory MMN response occurs within 50 ms of the deviant stimulus, and peaks after an additional 100–150 ms . MMN is thought to reflect auditory sensory memory or pre‐attentive processing . P300 is a positive‐going wave in the event‐related potential and is elicited during oddball paradigm with a latency of roughly 250–300 ms after deviant stimulus.…”

Section: Evidence Supporting the Nmdar Hypothesismentioning

confidence: 99%

“…Moreover, some studies have provided more direct evidence, showing the linkage of these attenuations and glutamate hypothesis in schizophrenia. For example, the plasma levels of glutamatergic amino acids were correlated with MMN amplitude attenuation in subjects in the early stages of psychosis . Another EEG and MRS study suggested that there were positive correlations between P300 amplitude and both the glutamine/glutamate ratio and the glutamine concentration in the anterior cingulate .…”

Section: Evidence Supporting the Nmdar Hypothesismentioning

confidence: 99%

Glutamate hypothesis in schizophrenia

Uno

Coyle

2019

Psychiatry Clin Neurosci

287

172

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Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability.

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“…However, here, during adolescence the reduction in MMN is significant and much greater in those with schizophrenia than bipolar disorder at the outset. A shared pathology may still be indicated because reduced MMN is related to N-methyl-D-aspartate receptor (NMDAR) dysfunction in schizophrenia and in first episode psychosis, and is associated with higher plasma levels of glutamate (Nagai et al, 2017).…”

Section: Discussionmentioning

confidence: 99%