The association between cortisol:C-reactive protein ratio and depressive fatigue is a function of CRP rather than cortisol

PURPOSE: Hormonal and inflammatory factors have been suggested as potentially influencing depressive state and depressive symptoms, but rarely compared for their relative contribution to these states and to specific depressive symptoms. This study examined cortisol:C-reactive protein (CRP) ratio, plus cortisol and CRP separately, as correlates of global depression and fatigue-related depression. PATIENTS AND METHODS: One hundred and twenty-six community volunteers from rural Australia provided saliva and serum samples, and also completed a depression inventory. RESULTS: There was a significant correlation between cortisol:CRP ratio and depression-related fatigue, and this resolved to the effects of CRP rather than cortisol. Most of the variance in this association came from patients who were “depressed”, and there were no significant gender associations. CONCLUSION: Inflammation, rather than HPA-axis activity, was associated with depression-related fatigue, supporting a model that places inflammation as a contributor to one of the major symptoms and predictors of depression. Individualization of therapy for depression-related fatigue in chronically stressed or physically ill patients might benefit from future research into cytokine therapy.