Plasma concentrations of granulocyte colony-stimulating factor (G-CSF) in patients with substance use disorders and comorbid major depressive disorder

Sandra Torres Galván,Roberto Muga,Pablo Romero-Sanchiz,María Flores-López,Francisco Javier Pavón,Antonia Serrano,Raquel Nogueira-Arjona,Nerea Requena-Ocaña,Nuria García-Marchena,Pedro Araos,Fernando Rodríguez De Fonseca,Fermín Mayoral,Oscar Porras-Perales

doi:10.1038/s41598-021-93075-1

Abstract

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.

Highlights

Granulocyte colony–stimulating factor (G-CSF) has raised much interest because of its role in cocaine addiction in preclinical models
The patients with cocaine use disorder (CUD) were younger than the patients with alcohol use disorder (AUD), and the percentage of participants with elementary education was greater in the alcohol subgroup
Because there was a significant association between lifetime substance use disorder (SUD) diagnosis and plasma concentrations of G-CSF, we explored relevant variables related to cocaine and alcohol addiction: the severity of SUD, duration of the last abstinence and problematic substance use

Summary

Introduction

Granulocyte colony–stimulating factor (G-CSF) has raised much interest because of its role in cocaine addiction in preclinical models. Other studies monitoring plasma concentrations of immune mediators have shown alcohol-induced dysregulation of certain chemokines related to immune responses such as SDF-1 [stromal derived factor (CXCL12)] and fractalkine (CX3CL1), which were found to be decreased in patients with alcohol use disorder (AUD)[14]. It has been reported that the gene expression of IL-17, IL-21, IL-23, and IL-35 was substantially higher in patients with MDD than in controls, which suggests that the expression of specific inflammatory genes may be a factor in the etiopathogenesis of depressive disorders These cytokines may affect the metabolism of neurotransmitters and neuroendocrine functions in the brain and may be markers and new potential therapeutic targets for recurrent depressive d isorders[31,32]

Methods

Results

Discussion

Conclusion