The Association Between Concentrations of Arginine, Ornithine, Citrulline and Major Depressive Disorder: A Meta-Analysis

Alterations in the peripheral (e.g., serum, plasma, platelet) concentrations of arginine and its related catabolic products (i.e., ornithine, citrulline) in the urea and nitric oxide cycles have been reported to be associated with major depressive disorder (MDD). The meta-analysis herein aimed to explore the association between the concentration of peripheral arginine, its catabolic products and MDD, as well as to discuss the possible role of arginine catabolism in the onset and progression of MDD. PubMed, EMBASE, PsycINFO and Web of Science were searched from inception to June 2020. The protocol for the meta-analysis herein has been registered at the Open Science Framework [https://doi.org/10.17605/osf.io/7fn59]. In total, 745 (47.5%) subjects with MDD and 823 (52.5%) healthy controls (HCs) from 13 articles with 16 studies were included. Fifteen of the included studies assessed concentrations of peripheral arginine, eight assessed concentrations of ornithine, and six assessed concentrations of citrulline. Results indicated that: (1) the concentrations of arginine, ornithine, and citrulline were not significantly different between individuals with MDD and HCs when serum, plasma and platelet are analyzed together, (2) in the subgroups of serum samples, the concentrations of arginine were lower in individuals with MDD than HCs, and (3) concurrent administration of psychotropic medications may be a confounding variable affecting the concentrations of arginine, ornithine, and citrulline. Our findings herein do not support the hypothesis that arginine catabolism between individuals with MDD and HCs are significantly different. The medication status and sample types should be considered as a key future research avenue for assessing arginine catabolism in MDD.