The Tryptophan System in Cocaine-Induced Depression.
Major 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.
['Fonseca|Francina|F|0000-0002-0779-6545', 'Mestre-Pintó|Joan-Ignasi|JI|0000-0003-0387-9375', 'Gómez-Gómez|Àlex|À|', 'Martinez-Sanvisens|Diana|D|', 'Rodríguez-Minguela|Rocío|R|', 'Papaseit|Esther|E|', 'Pérez-Mañá|Clara|C|0000-0001-6343-6918', 'Langohr|Klaus|K|', 'Valverde|Olga|O|0000-0003-2264-7852', 'Pozo|Óscar J|ÓJ|', 'Farré|Magí|M|0000-0001-8338-7543', 'Torrens|Marta|M|0000-0001-6222-4761', 'On Behalf Of Neurodep Group|||']
tryptophan cocaine use disorder serotonin kynurenine primary/substance-induced depression