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. Thi...

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Bibliographic Details
Authors: Fonseca, Francina, Mestre Pintó, Joan, Gómez Gómez, Àlex, Langohr, Klaus|||0000-0001-7075-9192, Pozo, Oscar, Farré, Magí, Torrens, Marta
Format: article
Publication Date:2020
Country:España
Institution:Universitat Politècnica de Catalunya (UPC)
Repository:UPCommons. Portal del coneixement obert de la UPC
Language:English
OAI Identifier:oai:upcommons.upc.edu:2117/345181
Online Access:https://hdl.handle.net/2117/345181
https://dx.doi.org/10.3390/jcm9124103
Access Level:Open access
Keyword:Primary/substance-induced depression
Cocaine use disorder
Tryptophan
Serotonin
Kynurenine
Classificació AMS::90 Operations research, mathematical programming
Àrees temàtiques de la UPC::Matemàtiques i estadística
Àrees temàtiques de la UPC::Ciències de la salut::Medicina
Description
Summary: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.