Fonseca Casals, Francina, 1972-Mestre-Pintó, Juan IgnacioGómez-Gómez, ÀlexMartínez-Sanvisens, DianaRodríguez-Minguela, RocíoPapaseit Fontanet, EstherPérez Mañá, ClaraLangohr, KlausValverde Granados, OlgaPozo Mendoza, Óscar J., 1975-Farré Albaladejo, MagíPérez Mañá, ClaraNeurodep Group2021-10-192021-10-192020Fonseca F, Mestre-Pintó JI, Gómez-Gómez À, Martinez-Sanvisens D, Rodríguez-Minguela R, Papaseit E, et al. The tryptophan system in cocaine-induced depression. J Clin Med. 2020 Dec 19; 9(12): 4103. DOI: 10.3390/jcm91241032077-0383http://hdl.handle.net/10230/48696Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine use disorder (CUD). The comorbid MDD might be primary-MDD (CUD-primary-MDD) or cocaine-induced MDD (CUD-induced-MDD), and their accurate diagnoses and treatment is a challenge for improving prognoses. This study aimed to assess the tryptophan/serotonin (Trp/5-HT) system with the acute tryptophan depletion test (ATD), and the kynurenine pathway in subjects with CUD-primary-MDD, CUD-induced-MDD, MDD and healthy controls. The ATD was performed with a randomized, double-blind, crossover, and placebo-controlled design. Markers of enzymatic activity of indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase, kynurenine aminotransferase (KAT) and kynureninase were also established. Following ATD, we observed a decrease in Trp levels in all groups. Comparison between CUD-induced-MDD and MDD revealed significant differences in 5-HT plasma concentrations (512 + 332 ng/mL vs. 107 + 127 ng/mL, p = 0.039) and the Kyn/5-HT ratio (11 + 15 vs. 112 + 136; p = 0.012), whereas there were no differences between CUD-primary-MDD and MDD. Effect size coefficients show a gradient for all targeted markers (d range 0.72-1.67). Results suggest different pathogenesis for CUD-induced-MDD, with lower participation of the tryptophan system, probably more related to other neurotransmitter pathways and accordingly suggesting the need for a different pharmacological treatment approach.application/pdfengCopyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/jcm9124103Cocaine use disorderKynureninePrimary/substance-induced depressionSerotoninTryptophaninfo:eu-repo/semantics/openAccess