Integration of proteinogenic amino acids in the pathogenesis of schizophrenia

Background

Schizophrenia (SCZ) is a severe mental disorder of multifactorial origin in which the role of amino acids is relatively unknown. Based on the hypothesis that there is an imbalance in amino acid levels in individuals with SCZ compared with healthy controls (HCs), the aim of this study was to identify the 20 proteinogenic amino acids involved in protein synthesis.

Methods

This study included 43 sex- and age-matched individuals: 20 HCs and 23 with SCZ diagnosed using the Diagnostic and Statistical Manual of Mental Disorders criteria. Using proton nuclear magnetic resonance, we identified the serum levels of the 20 amino acids proteinogenic. We perform multivariate statistical exploratory analyzes to identify compounds, quantify, and identify the main biomarkers of SCZ.

Results

We identified the serum levels of 19 of the 20 amino acids. Cysteine, the main precursor of glutathione, was not detected. Multivariate exploratory analysis identified lysine, Tryptophan (TRP), and glutamate as possible biomarkers of SCZ. Both lysine and TRP levels were lower and glutamate levels were higher in individuals with SCZ than in HCs. The observed reduction in plasma TRP levels in SCZ was attributed to the activation of the kynurenine pathway and has implications for serotonin synthesis. A strong positive correlation was observed between lysine and TRP, and a weak negative correlation between lysine and glutamate. This result is consistent with the lysine catalysis process because lysine degradation generates glutamate and favors an increase in dopamine.

Conclusions

The results are consistent with the lysine catalysis process because lysine degradation generates glutamate and favors an increase in dopamine. We were unable to identify any studies suggesting a relationship between lysine catabolism and SCZ pathophysiology, but we recognize this association as innovative.