title: 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.
authors.affiliation: Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain.
authors.forename: María
authors.initials: M
authors.lastname: Pedraz
authors.affiliation: Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Araos
authors.affiliation: Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: García-Marchena
authors.affiliation: Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.affiliation: Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Romero-Sanchiz
authors.affiliation: Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
authors.affiliation: Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Castilla-Ortega
authors.affiliation: Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain.
authors.forename: Fermín
authors.initials: F
authors.lastname: Mayoral-Cleries
authors.affiliation: Centro Provincial de Drogodependencia, Diputación de Málaga , Málaga , Spain.
authors.forename: Juan Jesús
authors.initials: JJ
authors.lastname: Ruiz
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques (IMIM) , Barcelona , Spain ; Facultat de Medicina, Universitat Autonoma de Barcelona , Barcelona , Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Pastor
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid , Madrid , Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III , Madrid , Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Barrios
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid , Madrid , Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III , Madrid , Spain.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
authors.affiliation: Department of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid , Madrid , Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III , Madrid , Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques (IMIM) , Barcelona , Spain ; Facultat de Medicina, Universitat Autonoma de Barcelona , Barcelona , Spain ; Institut de Neuropsiquiatria i Addiccions (INAD) del Parc de Salut MAR , Barcelona , Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Torrens
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques (IMIM) , Barcelona , Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III , Madrid , Spain ; Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra (CEXS-UPF) , Barcelona , Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.affiliation: Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III , Madrid , Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez De Fonseca
authors.affiliation: Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Pavón
keywords: abstinence; biomarker; cocaine use disorders; cytokine; endocannabinoid; outpatient; psychiatric comorbidity; sex