Granulocyte colony–stimulating factor (G-CSF) has raised much interest because of its role in cocaine addiction in preclinical models. We explored the plasma concentrations of G-CSF in patients diagnosed with substance use disorder (SUD) and highly comorbid psychiatric disorders. In particular, we investigated the association between G-CSF concentrations and comorbid major depressive disorder (MDD) in patients with cocaine and alcohol use disorders (CUD and AUD, respectively). Additionally, patients with MDD but not SUD were included in the study. Three hundred and eleven participants were enrolled in this exploratory study: 136 control subjects, 125 patients with SUD (SUD group) from outpatient treatment programs for cocaine (N = 60, cocaine subgroup) and alcohol (N = 65, alcohol subgroup), and 50 patients with MDD but not SUD (MDD group) from primary-care settings. Participants were assessed based on DSM-IV-TR criteria, and a blood sample was collected to examine the plasma concentrations of G-CSF. G-CSF concentrations were negatively correlated with age in the entire sample (r = − 0.233, p < 0.001) but not in the patients with MDD. G-CSF concentrations were lower in patients with SUD than in controls (p < 0.05), specifically in the cocaine subgroup (p < 0.05). Patients with SUD and comorbid MDD had lower G-CSF concentrations than patients with SUD but not comorbid MDD or controls (p < 0.05). In contrast, patients with MDD but not SUD showed no differences compared with their controls. The negative association between G-CSF concentrations and age in the sample was not observed in patients with MDD. G-CSF concentrations were decreased in patients with SUD and comorbid MDD but not in patients with MDD. Therefore, G-CSF may be useful to improve the stratification of patients with dual diagnosis seeking treatment. Further investigation is needed to explore the impact of sex and type of drug on the expression of G-CSF.
Aims: Granulocyte colony–stimulating factor (G-CSF) has raised much interest due to its role to cocaine addiction in preclinical models. We analyzed the circulating expression of G-CSF in abstinent chronic users of alcohol and/or cocaine with or without comorbid major depressive disorders to investigate the role of this trophic factor with complicated substance use disorders.Methods: We recruited 176 patients and 136 controls. Patients were divided in 50 patients with major depressive disorder (MDD) and 126 abstinent substance use disorders (SUD) patients undergoing treatments for alcohol (N=66) or cocaine (N=60) addiction according to DSM-IV-TR criteria. A blood sample was collected to examine plasma concentrations of G-CSF.Results: The plasma concentrations of G-CSF were significantly decreased in the cocaine group compared with the SUD control group. There was a sex dimorphism in the alcohol group, with lower G-CSF concentrations in women compared with men. Plasma concentrations of G-CSF were associated with abstinence and with the length of alcohol problems. The decrease in G-CSF was associated with comorbid MDD, a finding specific for SUD patients since there were no alterations of G-CSF primary settings MDD outpatients.Conclusions: Circulating G-CSF is reduced in SUD patients, being associated to comorbid MDD. A sex-dependent effect was observed in female AUD. Plasma G-CSF concentrations might be used as a predictor of length of chronic alcohol use and as a stratification role in the dual diagnosis in SUD. Further investigation is needed to explore the role of G-CSF as potential biomarker of pathogenic/prognosis in SUD population.
Palabras clave: alcohol, G-CSF, diferencias de sexo, comorbilidad psiquiátrica, trastornos del estado de ánimo. Descripción de los objetivos El Trastorno por uso de alcohol (TUA), produce alteraciones neurotóxicas en el Sistema Nervioso Central (SNC). La microglía modula la respuesta inmune e inflamatoria en el SNC a través de moléculas como el factor estimulante de colonias de granulocitos (G-CSF), que podrían ser empleadas como potenciales marcadores biológicos de daño producido por el consumo de alcohol. El objetivo es evaluar la asociación entre los niveles plasmáticos de G-CSF y la depresión, como trastorno más prevalentes de esta población. Material y método Se evaluaron clínicamente 46 pacientes TUA en abstinencia y se compararon con un grupo control de 46 sujetos. Mediante ELISAs, se cuantificaron la concentración plasmática de G-CSF y se realizaron análisis de covarianza (ANCOVAS). Resultado y conclusiones Un 43% de los pacientes TUA evaluados tenían comorbilidad con trastornos del estado de ánimo (TEA) (35%). Se encontraron diferencias en las prevalencias de consumo de sustancias entre hombres y mujeres (35% de los hombres consume cocaína). Respecto a los niveles de G-CSF, aparecen diferencias entre el grupo TUA y el control (p=0.007), así como diferencias debidas al género. En los pacientes con TUA hay relación entre el descenso de los niveles de G-CSF y el diagnóstico de TEA. Las concentraciones de C-CSF correlacionan con la edad. Hay una desregulación de las concentraciones plasmáticas de G-CSF en los TUA y trastornos TEA comórbidos. Se debe estudiar el papel neuroprotector del G-CSF ante la pérdida neuronal de los TUA. La inhibición de los niveles de G-CSF en las mujeres con TUA abre una puerta hacia el estudio de nuevas dianas terapéuticas. Investigar el papel de moléculas como el G-CSF en los TUA.
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