Global arginine bioavailability ratio is decreased in patients with major depressive disorder

Abstract

Arginine bioavailability may be decreased in MDD. This could impair the production of nitric oxide, and thus add to oxidative stress in the central nervous system.

Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects

“…These results are consistent with previous reports (Baranyi et al 2015; Hess et al 2017, Ali-Sisto et al 2018), where the authors showed decreased circulating levels of arginine and citrulline in MDD patients. No differences were observed for citrulline or arginine when comparing treatment with ketamine to placebo in healthy controls or MDD patients.…”

“…The increase in arginine levels is consistent with a recent study that also found a similar increase with esketamine treatment (Rotroff et al 2016). Other antidepressants have also been shown to have an effect in this pathway, with duloxetine resulting in an increase in the circulating levels of citrulline in a study with 12 MDD patients, while bupropion was associated with higher arginine levels in a study with 6 MDD patients (AliSisto et al 2018). The results of the study clearly demonstrate that ketamine is modulating the bioavailability of arginine in responders to ketamine treatment and that the nitric oxide cycle may be a potential mechanism of action of ketamine in responders to ketamine treatment.…”

“…Arginase activity, determined by the arginine/ ornithine ratio, had higher changes with responders relative to non-responders ( p = 0.044) at 230 min when adjusted for base-line levels, indicating the increased bioavailability of arginine may result from decreased arginase activity, similar to what was found in a recent study, where they also observed a decrease in arginase activity after first improvement of depression (Baranyi et al 2015; Hess et al 2017). A novel approach for a more precise measurement of the bioavailability of arginine and NO production is the Global Arginine Bioavailability Ratio (GABR) which is calculated as arginine/(citrulline + ornithine) (Baranyi et al 2015, Ali-Sisto et al 2018). Lower GABR has been associated with increased risk in cardiovascular disease (Sourij et al 2011), has been shown to be lower in PTSD subjects (Bersani et al 2016) and MDD subjects (Ali-Sisto et al 2018), and was negatively associated with PTSD symptom severity and was inversely correlated with inflammation markers IL-6 and TNF-α (Bersani et al 2016).…”

“…A novel approach for a more precise measurement of the bioavailability of arginine and NO production is the Global Arginine Bioavailability Ratio (GABR) which is calculated as arginine/(citrulline + ornithine) (Baranyi et al 2015, Ali-Sisto et al 2018). Lower GABR has been associated with increased risk in cardiovascular disease (Sourij et al 2011), has been shown to be lower in PTSD subjects (Bersani et al 2016) and MDD subjects (Ali-Sisto et al 2018), and was negatively associated with PTSD symptom severity and was inversely correlated with inflammation markers IL-6 and TNF-α (Bersani et al 2016). In our study, the GABR increased more at 230 min for responders relative to non-responders (0.34 vs 0.17, p = 0.027), but not at 1 day ( p = 0.244), consistent with the increased arginine levels at 230 min in responders.…”

Multi-omic biomarker identification and validation for diagnosing warzone-related post-traumatic stress disorder

“…Decreased coagulation in PTSD [10] Global Arginine Bioavailability Ratio (GABR) Metabolite ↓ ↑ ↑ GABR is decreased in patients with MDD [33]; previous decreased PTSD finding published in [34] GammaglutamyltyrosineMetabolite ↑ ↑ ↑ Gammaglutamyltyrosine negatively correlated with leukocyte telomere length [35] heart rate Physiological ↑ ↑ ↑ Elevated heart rate following trauma associated with development of PTSD [36] hsa-miR-133a-3p miRNA ↓ ↓ ↓ hsa-miR-192-5p miRNA ↓ ↓ ↑ Abundant in liver; associated with obesity and diabetes [37,38] hsa-miR-424-3p miRNA ↓ ↓ ↓ miR-424-3p has been associated with inflammation [39] hsa-miR-9-5p miRNA ↓ ↓ ↓ Enriched in brain tissue and regulates neurogenesis [40] Insulin Clinical Labs ↑ ↑ ↑ Increased insulin resistance in veterans with PTSD [41] ITIH2-VQF Protein ↓ ↓ ↓…”