Sex Differences in Psychiatric Comorbidity and Plasma Biomarkers for Cocaine Addiction in Abstinent Cocaine-Addicted Subjects in Outpatient Settings

Abstract

There are sex differences in the progression of drug addiction, relapse, and response to therapies. Because biological factors participate in these differences, they should be considered when using biomarkers for addiction. In the current study, we evaluated the sex differences in psychiatric comorbidity and the concentrations of plasma mediators that have been reported to be affected by cocaine. Fifty-five abstinent cocaine-addicted subjects diagnosed with lifetime cocaine use disorders (40 men and 15 women) and 73 healthy controls (48 men and 25 women) were clinically assessed with the diagnostic interview “Psychiatric Research Interview for Substance and Mental Disorders.” Plasma concentrations of chemokines, cytokines, N-acyl-ethanolamines, and 2-acyl-glycerols were analyzed according to history of cocaine addiction and sex, controlling for covariates age and body mass index (BMI). Relationships between these concentrations and variables related to cocaine addiction were also analyzed in addicted subjects. The results showed that the concentrations of chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 (CCL2/MCP-1) and chemokine (C-X-C motif) ligand 12/stromal cell-derived factor-1 (CXCL12/SDF-1) were only affected by history of cocaine addiction. The plasma concentrations of interleukin 1-beta (IL-1β), IL-6, IL-10, and tumor necrosis factor-alpha (TNFα) were affected by history of cocaine addiction and sex. In fact, whereas cytokine concentrations were higher in control women relative to men, these concentrations were reduced in cocaine-addicted women without changes in addicted men. Regarding fatty acid derivatives, history of cocaine addiction had a main effect on the concentration of each acyl derivative, whereas N-acyl-ethanolamines were increased overall in the cocaine group, 2-acyl-glycerols were decreased. Interestingly, N-palmitoleoyl-ethanolamine (POEA) was only increased in cocaine-addicted women. The covariate BMI had a significant effect on POEA and N-arachidonoyl-ethanolamine concentrations. Regarding psychiatric comorbidity in the cocaine group, women had lower incidence rates of comorbid substance use disorders than did men. For example, alcohol use disorders were found in 80% of men and 40% of women. In contrast, the addicted women had increased prevalences of comorbid psychiatric disorders (i.e., mood, anxiety, and psychosis disorders). Additionally, cocaine-addicted subjects showed a relationship between the concentrations of N-stearoyl-ethanolamine and 2-linoleoyl-glycerol and diagnosis of psychiatric comorbidity. These results demonstrate the existence of a sex influence on plasma biomarkers for cocaine addiction and on the presence of comorbid psychopathologies for clinical purposes.

Plasma Chemokines in Patients with Alcohol Use Disorders: Association of CCL11 (Eotaxin-1) with Psychiatric Comorbidity

“…In line with these observations, we reported recently that plasma levels of CXCL12 and chemokine C–X 3 –C motif ligand 1 (CX 3 CL1, also referred to fractalkine) are correlated to cocaine symptom severity, which allows stratifying the cocaine addicts in patients with different incidence of comorbid psychiatric disorders (6, 21). However, in the case of alcohol use disorders (AUD), plasma chemokines have been evaluated almost exclusively in the context of alcoholic hepatitis (18, 22).…”

“…Various studies have reported an association between both chemokines and abused drugs, mainly with cocaine. Recently, our group has reported a decrease in the plasma CXCL12 concentrations and a positive correlation between CX 3 CL1 concentrations and the cocaine symptom severity in abstinent cocaine-addicted subjects from outpatient setting (6, 21). In agreement with these clinical data, changes in the plasma concentrations of both chemokines have been observed in mice exposed to cocaine (21).…”

“…Recently, our group has reported a decrease in the plasma CXCL12 concentrations and a positive correlation between CX 3 CL1 concentrations and the cocaine symptom severity in abstinent cocaine-addicted subjects from outpatient setting (6, 21). In agreement with these clinical data, changes in the plasma concentrations of both chemokines have been observed in mice exposed to cocaine (21). However, another study in chronic cocaine users showed increased CXCL12 concentrations in the moment of admission for treatment, although they were decreased after 1 month of cocaine withdrawal (27).…”

Unchanged Levels of Soluble CD14 and IL-6 Over Time Predict Serious Non-AIDS Events in HIV-1-Infected People

“…12 Data are conflicting on whether cocaine and/or heroin increase sCD14 and IL-6 levels in persons with or without HIV infection. [13][14][15][16][17] The effects of illicit substances on inflammatory markers in HIV-1-infected persons on ART are unknown. Regardless, these data suggest that aggressive drug rehabilitation may be an additional intervention to lower SNAE risk in HIV-1-infected persons.…”

Neuroimmune mechanisms of psychostimulant and opioid use disorders

“…There are a number of studies that have examined the effects of cocaine on peripheral expression of inflammatory mediators (Summarized in Table ), including studies showing that acute cocaine alters cytokine expression in serum or in isolated peripheral leukocytes. In abstinent users that there are decreases in serum levels of the chemokine monocyte chemoattractant protein 1 (MCP‐1) and a number of pro‐inflammatory cytokines including IL‐6, IL‐17, and TNF‐α among others (Pedraz et al ., ; Maza‐Quiroga et al ., ; Gupta et al ., ). Of note, chemokines are frequently discussed using two different nomenclatures, which can lead to confusion.…”