Alteration in NMDAR‐related amino acids in first episode psychosis

Abstract

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.

Plasma amino acids profile in first-episode psychosis, unaffected siblings and community-based controls

“…Moreover, GLY and SER have been investigated as possible clinical markers for schizophrenia, with some studies demonstrating increased GLY and SER plasma levels in patients after antipsychotic treatment 23 , 65 ; no differences in patients medicated with different antipsychotics 3 , or lower GLY and SER plasma levels in patients in comparison to controls 66 , 67 . A recent study demonstrated high plasma GLN levels in drug-naïve FEP patients, which was negatively correlated with negative symptoms; however no differences in plasma GLN levels were found after treating these patients 68 .…”

Metabolomics approach revealed robust changes in amino acid and biogenic amine signatures in patients with schizophrenia in the early course of the disease

“…However, some discrepancy exists between studies. Cai et al (2012) 25 did not find altered Pro level in AP-naïve patients with FEP compared to CSs, however, Garip and Kayir (2019) 26 demonstrated that drug-naïve FEP patients had hyperprolinemia. Pro fulfils several of the classic criteria used to define neurotransmitters 27 and previous results indicate that L-Pro is a weak agonist of the Gly receptor and at both NMDA and non-NMDA Glu receptors 28 .…”

“…Boxplots of the statistically significant variation of the errors (residuals) of log-transformed biomarker ratios (derived by regressing out covariate effects) for control subjects and first episode (FEP) patients at baseline (before treatment with antipsychotics (AP)), after 0.6-year, and after 5.1-year treatment with AP. www.nature.com/scientificreports/ FEP compared to CSs, however, Garip and Kayir (2019) 26 demonstrated that drug-naïve FEP patients had hyperprolinemia. Pro fulfils several of the classic criteria used to define neurotransmitters 27 and previous results indicate that L-Pro is a weak agonist of the Gly receptor and at both NMDA and non-NMDA Glu receptors 28 .…”

Identification of cerebrospinal fluid and serum metabolomic biomarkers in first episode psychosis patients

“…Of note, myxalamid A was reported to be up-regulated in FEP patients at baseline but down-regulated in follow-up compared with HC. 4-hydroxyproline, as an NMDAR-related amino acid was reported to be elevated in FEP patients and inferred to induce a compensatory response to glutamatergic hypofunction [ 42 ]. Our pathway analysis also identified a potential involvement of the 4-hydroxyproline pathway, which is associated with executive dysfunction in schizophrenia [ 43 ].…”