Dual depression and Triptophan metabolites

The association of cocaine use disorder (CUD) and comorbid major depressive disorder (MDD) is characterized by high prevalence and poor treatment outcomes. CUD/MDD may be primary (primary MDD) or cocaine-induced (CUD-induced MDD). Specific biomarkers are needed to improve diagnoses and therapeutic approaches in this dual pathology. Among potential biomarkers we have explored tryptophan metabolites, including serotonin and kynurenin/kynurenic acid pathway as well as Platelet biomarkers [5-HT2A receptor and imidazoline receptor antisera selected (IRAS)/nischarin]. Studies were done at basal level and/or after acute tryptophan depletion (ATD). The comparison of IRAS/nischarin in the different subject groups during/after ATD showed opposite modulations (i.e., increases and decreases) in response to low plasma tryptophan levels with significant differences discriminating between the subgroups of CUD with primary MDD and CUD-induced MDD. These specific alterations suggested that platelet IRAS/nischarin might be useful as a biomarker to discriminate between primary and CUD-induced MDD in this dual pathology.Data on the kynurenine/Kynurenic acid will be also presented and discussed.