Plasma concentrations of Granulocyte Colony-Stimulating Factor (G-CSF) in Patients with Substance Use Disorders and Comorbid Major Depressive Disorders

Abstract

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.

Granulocyte-colony stimulating factor (G-CSF) enhances cocaine effects in the nucleus accumbens via a dopamine release-based mechanism

“…Accordingly, immune dysregulation has been implicated in addiction, and only recently have studies begun to examine the mechanistic link between altered immune function and the pathology underlying addictive disorders 2,[4][5][6][7][8] . Granulocyte-colony stimulating factor (G-CSF), a cytokine, is regulated by cocaine in rodents 6 and humans 9 , and is a potent modulator of behavioral plasticity induced by repeated cocaine exposure where it increases cocaine selfadministration under low effort schedules of reinforcement, enhances motivation for cocaine, increases cocaine conditioned place preference, increases sensitization, and alters drug seeking in both males and females 5,6,10 . While the behavioral effects are well-characterized, the neural basis for how this cytokine enhances stimulant effects remains to be elucidated.…”