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

Abstract

Major depressive disorder (MDD) is the most prevalent comorbid mental disorder among people with substance use disorders. The MDD can be both primary and substance-induced and its accurate diagnosis represents a challenge for clinical practice and treatment response. Recent studies reported alterations in the circulating expression of inflammatory mediators in patients with psychiatric disorders, including those related to substance use. The aim of the study was to explore TNF-α, IL-1β, CXCL12, CCL2, CCL11 (eotaxin-1) and CX3CL1 (fractalkine) as potential biomarkers to identify comorbid MDD and to distinguish primary MDD from substance-induced MDD in patients with substance disorders. Patients diagnosed with cocaine (CUD, n = 64) or alcohol (AUD, n = 65) use disorders with/without MDD were recruited from outpatient treatment programs [CUD/non-MDD (n = 31); CUD/primary MDD (n = 18); CUD/cocaine-induced MDD (N = 15); AUD/non-MDD (n = 27); AUD/primary MDD (n = 16) and AUD/alcohol-induced MDD (n = 22)]. Sixty-two healthy subjects were also recruited as control group. Substance and mental disorders were assessed according to “Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision” (DSM-IV-TR) and a blood sample was collected for determinations in the plasma. The cocaine group showed lower TNF-α (p<0.05) and CCL11 (p<0.05), and higher IL-1β (p<0.01) concentrations than the control group. In contrast, the alcohol group showed higher IL-1β (p<0.01) and lower CXCL12 (p<0.01) concentrations than the control group. Regarding MDD, we only observed alterations in the cocaine group. Thus, CUD/MDD patients showed lower IL-1β (p<0.05), CXCL12 (p<0.05) and CCL11 (p<0.05), and higher CXC3CL1 (p<0.05) concentrations than CUD/non-MDD patients. Moreover, while CUD/primary MDD patients showed higher CCL11 (p<0.01) concentrations than both CUD/non-MDD and CUD/cocaine-induced MDD patients, CUD/cocaine-induced MDD patients showed lower CXCL12 (p<0.05) concentrations than CUD/non-MDD patients. Finally, a logistic regression model in the cocaine group identified CXCL12, CCL11 and sex to distinguish primary MDD from cocaine-induced MDD providing a high discriminatory power. The present data suggest an association between changes in inflammatory mediators and the diagnosis of primary and substance-induced MDD, namely in CUD patients.

The Potential Role of Dysfunctions in Neuron-Microglia Communication in the Pathogenesis of Brain Disorders

“…In those affected by moderate-severe depression, the serum level of CX3CL1 was elevated when compared to that in the control patients [ 236 ]. A similar observation was reported in plasma samples from patients diagnosed with major depressive disorder with comorbid cocaine addiction [ 237 ]. The level of CX3CL1 was thus suggested as a potential biomarker for depression and anxiety in the course of colorectal cancer, due to the raised serum level of this protein identified in patients with this condition [ 238 ].…”

Depression and Cardiovascular Disease: The Viewpoint of Platelets

“…Increased plasma levels of fractalkine in moderate-severe depressed patients compared to control subjects was found [313] and this result was confirmed by other studies, in which a correlation between fractalkine plasma levels and the severity of depressive symptoms was identified [314,315] (Table 2). However, considering the scarcity of information about circulating levels of fractalkine in association with depression, further studies are needed, also taking into account the possible confounding factors (e.g., age, BMI) and the heterogeneity of MDD.…”

Epigenetic scores for the circulating proteome as tools for disease prediction

“…The mechanisms by which CCL11 may be related to depression are unclear; however, CCL11 is thought to mediate peripheral and central nervous system inflammation, with evidence that it has microglial and astrocytic targets 49 . As CCL11 is suggested as one of several cytokine plasma markers that may identify those with depression [50][51][52][53] , circulating DNAm proxies could prove to be relevant markers for the stratification of psychiatric illness risk.…”