Associations of Serum Cytokines, Growth Factors, and High-Sensitivity C-Reactive Protein Levels in Patients with Major Depression with and without Type 2 Diabetes Mellitus: An Explanatory Investigation

Abstract

Takashi Hoshikawa,1 Naomichi Okamoto,1 Tomoya Natsuyama,1 Rintaro Fujii,1 Atsuko Ikenouchi,1 Yuichi Honma,2 Masaru Harada,2 Reiji Yoshimura1 1Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, 8078555, Japan; 2 3rd Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, 8078555, JapanCorrespondence: Reiji YoshimuraDepartment of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, 8078555, Japan, Tel [phone], Fax [phone], Email [email protected]: We investigated the serum levels of cytokines, including interleukin 1β (IL-β), IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and growth factors, including brain-derived neurotrophic factor, vascular endothelial growth factor, and insulin-like growth factor 1, and their association with major depression in patients with and without type 2 diabetes mellitus. We also investigated the response to antidepressant treatment in both groups.Patients and Methods: Forty-one patients with major depression were recruited at the University Hospital of Occupational and Environmental Health. All patients were diagnosed with major depression using the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Type 2 diabetes mellitus was diagnosed according to the criteria of the Japan Diabetes Society. Six healthy controls with no history of psychiatric or physical diseases were also enrolled. Serum levels of several cytokines, growth factors, and high-sensitivity C-reactive protein (hs-CRP) were measured. The clinical symptoms of patients with major depression were assessed using the Montgomery-Asberg Depression Rating Scale.Results: Significant differences in cytokines, growth factors, and hs-CRP were observed between the major depression and healthy control groups. Serum TNF-α levels were significantly higher in patients with major depression and type 2 diabetes mellitus than in those without type 2 diabetes mellitus. In the major depression group, serum IL-6 and hs-CRP levels tended to be higher in patients with type 2 diabetes mellitus than in those without. Several correlations among cytokines, growth factors, and hs-CRP were observed in patients with major depression with and without type 2 diabetes mellitus. Responses to pharmacological interventions for major depression did not differ between patients with and without type 2 diabetes mellitus.Conclusion: Serum levels of TNF-α, hs-CRP, and IL-6 were different between patients with major depression with and without type 2 diabetes mellitus. Also, correlations were found between serum levels of cytokines, growth factors, and hs-CRP in patients with major depression. Inflammatory factors, which may be associated with growth factors, may be involved in the pathophysiology of major depression, particularly among patients with comorbid type 2 diabetes mellitus.Keywords: major depression, diabetes mellitus, cytokine, growth factor, high-sensitivity C-reactive protein, brain-derived neurotrophic factor

Keywords

• major depression
• diabetes mellitus
• cytokine
• growth factor
• high-sensitivity c-reactive protein
• brain-derived neurotrophic factor