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

PLoS One. 2019 Mar 14;14(3):e0213791. doi: 10.1371/journal.pone.0213791. eCollection 2019.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcoholism / blood
  • Alcoholism / diagnosis*
  • Alcoholism / epidemiology
  • Biomarkers / blood*
  • Case-Control Studies
  • Cocaine-Related Disorders / blood
  • Cocaine-Related Disorders / diagnosis*
  • Cocaine-Related Disorders / epidemiology
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / diagnosis*
  • Depressive Disorder, Major / epidemiology
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Male
  • Middle Aged
  • Prevalence
  • Spain / epidemiology
  • Substance-Related Disorders / blood
  • Substance-Related Disorders / diagnosis*
  • Substance-Related Disorders / epidemiology

Substances

  • Biomarkers
  • Inflammation Mediators

Grants and funding

This work was supported by RETICS Red de Trastornos Adictivos (RD12/0028/0021, RD12/0028/0009, RD16/0017/0001, RD16/0017/0010, and RD 16/0017/003) funded by Instituto de Salud Carlos III (ISC-III) and European Regional and European Regional Development Funds-European Union (ERDF-EU); Research projects funded by Ministerio de Economía y Competitividad and ISC-III (PI09/02121; PI12/01838, PI16/01698, PI16/01953); Research project funded by Ministerio de Sanidad, Servicios Sociales e Igualdad and Plan Nacional sobre Drogas (043/2017 and 2012I054); Research project funded by Consejería de Economía, Innovación y Ciencia, Junta de Andalucía and ERDF-EU (CTS-433); Suport Grups de Recerca AGAUR Gencat 2017 SGR 316 and SGR530). NGM received a training research grant funded by Consejería de Salud y Bienestar Social, Junta de Andalucía (EF-0202-2017); AS and FJP hold a Miguel Servet research contract funded by ISC-III and ERDF-EU (CP14/00173 and CP14/00212, respectively); PA received a Plan Propio grant from Universidad de Málaga (Incorporación Doctores CI-17-415). These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.