title: Plasma concentrations of oleoylethanolamide and other acylethanolamides are altered in alcohol-dependent patients: effect of length of abstinence.
abstract: Acylethanolamides are a family of endogenous lipid mediators that are involved in physiological and behavioral processes associated with addiction. Recently, oleoylethanolamide (OEA) has been reported to reduce alcohol intake and relapse in rodents but the contribution of OEA and other acylethanolamides in alcohol addiction in humans is unknown. The present study is aimed to characterize the plasma acylethanolamides in alcohol dependence. Seventy-nine abstinent alcohol-dependent subjects (27 women) recruited from outpatient treatment programs and age-/sex-/body mass-matched healthy volunteers (28 women) were clinically assessed with the diagnostic interview PRISM according to the DSM-IV-TR after blood extraction for quantification of acylethanolamide concentrations in the plasma. Our results indicate that all acylethanolamides were significantly increased in alcohol-dependent patients compared with control subjects (p < 0.001). A logistic model based on these acylethanolamides was developed to distinguish alcohol-dependent patients from controls and included OEA, arachidonoylethanolamide (AEA) and docosatetraenoylethanolamide (DEA), providing a high discriminatory power according to area under the curve [AUC = 0.92 (95%CI: 0.87-0.96), p < 0.001]. Additionally, we found a significant effect of the duration of alcohol abstinence on the concentrations of OEA, AEA and DEA using a regression model (p < 0.05, p < 0.01 and p < 0.001, respectively), which was confirmed by a negative correlation (rho = -0.31, -0.40 and -0.44, respectively). However, acylethanolamides were not influenced by the addiction alcohol severity, duration of problematic alcohol use or diagnosis of psychiatric comorbidity. Our results support the preclinical studies and suggest that OEA, AEA and DEA are altered in alcohol-dependence during abstinence and that might act as potential markers for predicting length of alcohol abstinence.
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Garcia-Marchena
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Pavon
authors.affiliation: Grup de Recerca en Farmacología Integrada i Neurociencia de Sistemes, Programa de Recerca en Neurociencia, IMIM (Hospital del Mar Medical Research Institute), Spain.|Department de Farmacologia, Toxicologia i Terapeutica, Facultat de Medicina, Universitat Autonoma de Barcelona, Spain.|CIBER Fisiopatologia Obesidad y Nutricion (CIBERObn), ISCIII, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Pastor
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Araos
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Pedraz
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Romero-Sanchiz
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Calado
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Suarez
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Castilla-Ortega
authors.affiliation: Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Orio
authors.affiliation: Grup de Recerca en Farmacología Integrada i Neurociencia de Sistemes, Programa de Recerca en Neurociencia, IMIM (Hospital del Mar Medical Research Institute), Spain.|Department de Farmacologia, Toxicologia i Terapeutica, Facultat de Medicina, Universitat Autonoma de Barcelona, Spain.|CIBER Fisiopatologia Obesidad y Nutricion (CIBERObn), ISCIII, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Boronat
authors.affiliation: Institut de Neuropsiquiatria i Adiccions (INAD) del Parc de Salut MAR, Spain.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.|Department of Psychiatry, Univ Autonoma de Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Torrens
authors.affiliation: Departamento de Psiquiatria, Facultad de Medicina, Universidad Complutense, Spain.|Instituto de Investigación Hospital 12 de Octubre, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rubio
authors.affiliation: Grup de Recerca en Farmacología Integrada i Neurociencia de Sistemes, Programa de Recerca en Neurociencia, IMIM (Hospital del Mar Medical Research Institute), Spain.|CIBER Fisiopatologia Obesidad y Nutricion (CIBERObn), ISCIII, Spain.|Facultat de Ciencies de la Salut i de la Vida, Universidat Pompeu Fabra (CEXS-UPF), Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodriguez de Fonseca
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
mesh_terms: D000328:Adult; D064829:Alcohol Abstinence; D000437:Alcoholism / Q000097:blood*; D000577:Amides; D001095:Arachidonic Acids / Q000097:blood; D016022:Case-Control Studies; D003687:Dehydroepiandrosterone / Q000097:blood; D063388:Endocannabinoids / Q000097:blood; D004983:Ethanolamines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009829:Oleic Acids / Q000097:blood; D010169:Palmitic Acids / Q000097:blood; D011092:Polyethylene Glycols; D053284:Polyunsaturated Alkamides / Q000097:blood; D013229:Stearic Acids / Q000097:blood; D013997:Time Factors
chemical_list: D000577:Amides; D001095:Arachidonic Acids; D063388:Endocannabinoids; D004983:Ethanolamines; D009829:Oleic Acids; C440229:Oleylethanolamide; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D013229:Stearic Acids; C054694:polyoxyethyleneamine; C466089:stearoylethanolamide; C488250:oleoylethanolamide; D011092:Polyethylene Glycols; D003687:Dehydroepiandrosterone; C005958:palmidrol; C078814:anandamide
keywords: DSM-IV-TR; abstinence; acylethanolamides; alcohol use disorder; oleoylethanolamide; psychiatric comorbidity