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

• Published in: Journal of affective disorders 2018-03, Vol.229, p.145-151
• Main Authors: Ali-Sisto, Toni, Tolmunen, Tommi, Viinamäki, Heimo, Mäntyselkä, Pekka, Valkonen-Korhonen, Minna, Koivumaa-Honkanen, Heli, Honkalampi, Kirsi, Ruusunen, Anu, Nandania, Jatin, Velagapudi, Vidya, Lehto, Soili M.
• Format: Article
• Language: English
• Subjects: Arginine; Citrulline; Global arginine bioavailability ratio; Major depressive disorder; Ornithine
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2017.12.030

Major depressive disorder (MDD) is characterized by increased oxidative and nitrosative stress. We compared nitric oxide metabolism, i.e., the global arginine bioavailability ratio (GABR) and related serum amino acids, between MDD patients and non-depressed controls, and between remitted and non-remitted MDD patients. Ninety-nine MDD patients and 253 non-depressed controls, aged 20–71 years, provided background data via questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of ornithine, arginine, citrulline, and symmetric and asymmetric dimethylarginine. GABR was calculated as arginine divided by the sum of ornithine plus citrulline. We compared the above measures between: 1) MDD patients and controls, 2) remitted (n=33) and non-remitted (n = 45) MDD patients, and 3) baseline and follow-up within the remitted and non-remitted groups. Lower arginine levels (OR 0.98, 95% CI 0.97–0.99) and lower GABR (OR 0.13, 95% CI 0.03–0.50) were associated with the MDD vs. the non-depressed group after adjustments for potential confounders. The remitted group showed a decrease in GABR, arginine, and symmetric dimethylarginine, and an increase in ornithine after the follow-up compared with within-group baseline values. The non-remitted group displayed an increase in arginine and ornithine levels and a decrease in GABR. No significant differences were recorded between the remitted and non-remitted groups. The MDD group was not medication-free. 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. •A decreased bioavailability of arginine was associated with depression.•Arginine bioavailability increased within both remitted and non-remitted groups.•No significant differences were observed between remitted vs. non-remitted groups.