Rebeca Vidal1, Nuria García-Marchena2, Esther O'Shea1, Nerea Requena-Ocaña3, María Flores-López3, Pedro Araos4, Antonia Serrano3, Juan Suárez3, Gabriel Rubio5, Fernando Rodríguez de Fonseca3, María Isabel Colado6, Francisco Javier Pavón7. 1. Departamento Farmacología, Facultad de Medicina, Universidad Complutense, Madrid, Spain. 2. Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain; Unidad de Adicciones, Servicio de Medicina Interna, Institut Germans Trias i Pujol (IGTP), Badalona, Spain. 3. Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. 4. Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain; Facultad de Psicología, Universidad de Málaga, Málaga, Spain. 5. Hospital Universitario, 12 de Octubre, Madrid, Spain. 6. Departamento Farmacología, Facultad de Medicina, Universidad Complutense, Madrid, Spain. Electronic address: colado@med.ucm.es. 7. Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain; Unidad Gestión Clínica del Corazón, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: javier.pavon@ibima.eu.
Abstract
BACKGROUND: Alterations in tryptophan (TRP) metabolism has been linked to drug exposure and mental disorders. However, most of studies have been performed without considering the co-occurrence of both disorders in the context of addiction. This cross-sectional study examines TRP metabolism through the serotonin (5-HT) and kynurenine (KYN) pathways in subjects with alcohol use disorders (AUD) and high prevalence of psychiatric comorbidity. METHODS: For this purpose, male and female abstinent AUD patients (N = 130) and healthy controls (N = 80) were clinically evaluated for substance use and mental disorders, and blood samples were collected to determine plasma concentrations of TRP, 5-HT, KYN and kynurenic acid (KA) using high performance liquid chromatography. Clinical and biochemical variables were analyzed for potential associations considering AUD, psychiatric comorbidity and sex. RESULTS: TRP concentrations were significantly associated with an interaction effect between AUD diagnosis and sex (p < .01): TRP concentrations were lower in male AUD patients but higher in female AUD patients compared with their controls. KYN and KA concentrations were significantly associated with AUD diagnosis (p < .01 and p < .05, respectively). Thus, AUD patients showed significantly higher KYN concentrations and lower KA concentrations than controls. Regarding 5-HT concentrations, there were sex differences in the alcohol group (p < .05) and female AUD patients showed lower 5-HT concentrations than male AUD patients. Moreover, there was a significant interaction effect between psychiatric comorbidity and sex on TRP concentrations in the alcohol group (p < .01). Whereas male patients with both comorbid substance use and mental disorders showed lower TRP concentrations than male non-comorbid patients, female patients with comorbid mental disorders showed higher TRP concentrations than female non-comorbid patients. CONCLUSION: While alterations in the KYN pathway appear to be directly associated with a history of AUD, altered TRP concentrations are associated with the presence of comorbid psychiatric disorders. Finally, sex differences in TRP metabolism must be considered in future studies.
BACKGROUND: Alterations in tryptophan (TRP) metabolism has been linked to drug exposure and mental disorders. However, most of studies have been performed without considering the co-occurrence of both disorders in the context of addiction. This cross-sectional study examines TRP metabolism through the serotonin (5-HT) and kynurenine (KYN) pathways in subjects with alcohol use disorders (AUD) and high prevalence of psychiatric comorbidity. METHODS: For this purpose, male and female abstinent AUDpatients (N = 130) and healthy controls (N = 80) were clinically evaluated for substance use and mental disorders, and blood samples were collected to determine plasma concentrations of TRP, 5-HT, KYN and kynurenic acid (KA) using high performance liquid chromatography. Clinical and biochemical variables were analyzed for potential associations considering AUD, psychiatric comorbidity and sex. RESULTS:TRP concentrations were significantly associated with an interaction effect between AUD diagnosis and sex (p < .01): TRP concentrations were lower in male AUD patients but higher in female AUD patients compared with their controls. KYN and KA concentrations were significantly associated with AUD diagnosis (p < .01 and p < .05, respectively). Thus, AUD patients showed significantly higher KYN concentrations and lower KA concentrations than controls. Regarding 5-HT concentrations, there were sex differences in the alcohol group (p < .05) and female AUD patients showed lower 5-HT concentrations than male AUD patients. Moreover, there was a significant interaction effect between psychiatric comorbidity and sex on TRP concentrations in the alcohol group (p < .01). Whereas male patients with both comorbid substance use and mental disorders showed lower TRP concentrations than male non-comorbid patients, female patients with comorbid mental disorders showed higher TRP concentrations than female non-comorbid patients. CONCLUSION: While alterations in the KYN pathway appear to be directly associated with a history of AUD, altered TRP concentrations are associated with the presence of comorbid psychiatric disorders. Finally, sex differences in TRP metabolism must be considered in future studies.
Authors: Joon Hwan Jang; So Young Yoo; Yae Eun Park; Mi-Jung Ji; Hyun-Mee Park; Ji Hyun Back; Ji Yoon Lee; Dai Jin Kim; Ji Eun Lee; Jung-Seok Choi Journal: Front Pharmacol Date: 2022-04-11 Impact factor: 5.988
Authors: Nuria García-Marchena; Alberto Marcos; María Flores-López; Mario Moreno-Fernández; Nerea Requena-Ocaña; Oscar Porras-Perales; Sandra Torres-Galván; Pedro Araos; Antonia Serrano; Roberto Muga; Juan Jesús Ruiz-Ruiz; Fernando Rodríguez de Fonseca; Emilio Ambrosio; Francisco Javier Pavón-Morón Journal: Biomedicines Date: 2022-05-14