A Biomarker to Differentiate between Primary and Cocaine-Induced Major Depression in Cocaine Use Disorder: The Role of Platelet IRAS/Nischarin (I1-Imidazoline Receptor)

Abstract

The association of cocaine use disorder (CUD) and comorbid major depressive disorder (MDD; CUD/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. Platelet biomarkers [5-HT2A receptor and imidazoline receptor antisera selected (IRAS)/nischarin] were assessed by Western blot in subjects with CUD and primary MDD (n = 16) or CUD-induced MDD (n = 9; antidepressant free, AD−; antidepressant treated, AD+) and controls (n = 10) at basal level and/or after acute tryptophan depletion (ATD). Basal platelet 5-HT2A receptor (monomer) was reduced in comorbid CUD/MDD subjects (all patients: 43%) compared to healthy controls, and this down-regulation was independent of AD medication (decreases in AD−: 47%, and in AD+: 40%). No basal differences were found for IRAS/nischarin contents in AD+ and AD− comorbid CUD/MDD subjects. 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.

The Tryptophan System in Cocaine-Induced Depression

“…According to these results and previously published research [ 44 ] it can be presumed that the biochemical basis of induced-MDD differs from primary-MDD. The neurobiological basis for induced depression in CUD does not seem to be primarily mediated by 5-HT dysfunction and other neurotransmitter pathways may be involved.…”

Inflammatory mediators and dual depression: Potential biomarkers in plasma of primary and substance-induced major depression in cocaine and alcohol use disorders

“…Because there was a strong association between alterations in the plasma expression of certain inflammatory mediators and comorbid MDD, we extended our study in CUD patients diagnosed with primary and cocaine-induced MDD. In fact, the differentiation between primary and substance-induced MDD in dual pathology is a field of study to be explored, and a recent research has showed that platelet IRAS/nischarim (I 1 -Imidazoline receptor) could discriminate between primary MDD and cocaine-induced MDD in CUD patients [ 51 ]. In our study, we have observed differences in the plasma expression of CCL11 and CXCL12 according to the type of MDD.…”

Impact of Nischarin on EMT regulators in breast cancer cell lines

“…In humans, its expression has been identified in several tissues ( 5 , 7 ). The roles of Nischarin in humans include serving as a neuroprotective protein that regulates neuronal migration ( 7 ), a regulator of brain function ( 8 , 9 ), a regulator of blood pressure ( 10 ) and a tumor suppressor of ovarian and breast cancer ( 1 , 2 ).…”