Characterizing amino-acid biosignatures amongst individuals with schizophrenia: a case–control study

Abstract

Amino acids and derivatives participate in the biosynthesis and downstream effects of numerous neurotransmitters. Variations in specific amino acids have been implicated in the pathophysiology of schizophrenia. Herein, we sought to compare levels of amino acids and derivatives between subjects with schizophrenia and healthy controls (HC). Two hundred and eight subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria (DSM-IV)-defined schizophrenia and 175 age- and sex-matched HC were enrolled. The levels of twenty-five amino acids and seven related derivatives were measured in plasma samples using hydrophilic interaction liquid chromatography (HILIC) liquid chromatography-tandem mass spectrometry (LC-MS). After controlling for age, sex and body mass index (BMI), four amino acids and derivatives (i.e., cysteine, GABA, glutamine and sarcosine) were observed to be higher in the schizophrenia group when compared with HC; seven amino acids and derivatives were lower in the schizophrenia group (i.e., arginine, L-ornithine, threonine, taurine, tryptophan, methylcysteine, and kynurenine). Statistically significant differences in plasma amino-acid profiles between subjects with first-episode vs. recurrent schizophrenia for aspartate and glutamine were also demonstrated using generalized linear models controlling for age, sex, and BMI. The differences in amino acids and derivatives among individuals with schizophrenia when compared to HC may represent underlying pathophysiology, including but not limited to dysfunctional proteinogenic processes, alterations in excitatory and inhibitory neurotransmission, changes in ammonia metabolism and the urea cycle. Taken together, amino-acid profiling may provide a novel stratification approach among individuals with schizophrenia.

Immune and Neuroendocrine Trait and State Markers in Psychotic Illness: Decreased Kynurenines Marking Psychotic Exacerbations

“…However, although our patients exhibited state and trait immune activation, the GTP-CH1 pathway did not differentiate patients from controls (except for nitrite) and the IDO pathway appeared overall downregulated in patients vs. controls. Although this finding contradicts our original hypothesis of immune-activated IDO upregulation, it is in line with results from two recent amino-acid profiling studies (one cross-sectional study in 208 first episode psychosis patients and one 7month follow-up study in 38 schizophrenia patients) in which tryptophan and kynurenine were decreased in participants with schizophrenia vs. controls (26,27).…”

A pilot case-control study on the association between N-acetyl derivatives in serum and first-episode schizophrenia

“…N-acetyl group metabolites are the acetylated variant of amino acids and organic acids, which are a general class of endogenous compounds characterized by a conjugated system consisting of an acetyl group and nitrogen moiety. Two of our previous studies have already confirmed that some of the amino acids and organic acids might be associated with the pathogenesis and progression of schizophrenia (Cao et al, 2018a;Cao et al, 2018b). Also, Nacetyl-glucosamine has been shown to act as a nutrient sensor and mediator of insulin resistance (Wells et al, 2003).…”

Amino acids and acylcarnitines as potential metabolomic markers of schizophrenia: new approaches to diagnostics and therapy

“…Cao (2018) áûëî ïîêàçàíî ïîâûøåíèå êîíöåíòðàöèé ñûâîðîòî÷íîãî öèñòåèíà, γ-àìèíîìàñëÿíîé êèñëîòû, ãëóòàìèíà è ñàðêîçèíà è ñíèaeåíèå àðãèíèíà, L-îðíèòèíà, òðåîíèíà, òàóðèíà, òðèïòîôàíà, ìåòèëöèñòåèíà è êèíóðåíèíà â ãðóïïå áîëüíûõ øèçîôðåíèåé ñ êîððåêòèðîâêîé íà ïîë, âîçðàñò è èíäåêñ ìàññû òåëà ïî ñðàâíåíèþ ñî çäîðîâûìè ëèöàìè. Êðîìå òîãî, ó ïàöèåíòîâ ñ ïåðâûì ýïèçîäîì øèçîôðåíèè â îòëè÷èå îò ïàöèåíòîâ ñ ðåöèäèâèðóþùåé øèçîôðåíèåé çàôèêñèðîâàíî ñíèaeåíèå óðîâíÿ àñïàðòàòà è ïîâûøåíèå óðîâíÿ ãëóòàìèíà â ñûâîðîòêå êðîâè [37]. Ïðåäñòàâëÿþò èíòåðåñ ïðîâåäåííûå â ïîñëåäíåå âðåìÿ èññëåäîâàíèÿ â îòíîøåíèè ñâÿçè ïîâûøåíèÿ äåãðàäàöèè òðèïòîôàíà ñ èçìåíåíèåì öåëîñòíîñòè áåëîãî âåùåñòâà ìîçãà è óðîâíåì ãëóòàìàòà áåëîãî âåùåñòâà ìîçãà ó ïàöèåíòîâ ñ øèçîôðåíèåé.…”