Serum Cortisol, Nesfatin-1, and IL-1β: Potential Diagnostic Biomarkers in Elderly Patients with Treatment-Resistant Depression

Abstract

Aim Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder (MDD), especially elderly patients. As individuals with TRD are at an increased risk of committing suicide and pose a higher risk of relapse, early diagnostic biomarkers of TRD and a better understanding of the resistance mechanism are highly needed. This study aimed to determine whether serum cortisol, nesfatin-1, and pro-inflammatory cytokines can be used as biomarkers for the diagnosis of elderly patients with TRD. Methods Thirty elderly patients with TRD were selected as the TRD group. Thirty elderly patients with MDD who were effectively treated with conventional antidepressants were selected as the non-TRD group. The baseline levels of serum cortisol, nesfatin-1, and pro-inflammatory cytokines were measured and compared, and their diagnostic values were evaluated using the receiver operating characteristic (ROC) curve method for discriminating patients with TRD from those without TRD. Results Serum cortisol, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were significantly higher in the non-TRD and TRD groups than in the control group. Moreover, serum cortisol, CRP, TNF-α, and IL-6 levels in the TRD group were significantly lower than those in the non-TRD group. Furthermore, serum nesfatin-1 levels in the non-TRD group were significantly lower than those in the control and TRD groups, while the serum IL-1β levels in the non-TRD group were significantly higher than those in the control and TRD groups. Additionally, an ROC analysis revealed an area under the curve (AUC) of 0.929 for the combination of nesfatin-1 and IL-1β and an AUC of 0.956 for the combination of cortisol, nesfatin-1, and IL-1β in discriminating elderly patients with TRD from those without non-TRD. Conclusion Serum cortisol, nesfatin-1, and IL-1β may be potential diagnostic biomarkers for discriminating elderly patients with TRD from those without TRD.

Biological correlates of treatment resistant depression: a review of peripheral biomarkers

“…Sanchez-Carro et al ( 55 ) provided data supporting the role of TNF-α in discriminating between TRD and HC using a machine learning approach. These findings were replicated in a case–control cross-sectional study on elderly TRD patients, where TNF-α levels were significantly higher in TRD than in the HC group ( 65 ). In addition, in a double-blind, randomized, placebo-controlled trial, Strawbridge et al ( 59 ) found that the baseline pro-inflammatory proteins, including TNF-α, were significantly higher in TRD patients than in HC, after controlling for gender, age, childhood adversity and BMI.…”

“…With respect to IL-1, available data are still inconsistent. In fact, while Uint et al ( 62 ) found higher IL-1b plasma levels in TRD compared to HC, Zincir et al ( 67 ) and Wu et al ( 65 ) found lower IL-1b levels of in TRD patients.…”

“…All available studies found increased plasma levels of IL-6 in TRD patients compared to HC ( 28 , 49 , 54 , 65 ).…”

Late Life Depression: A Narrative Review

“…Serum cortisol, nesfatin-1 and IL-beta have been diagnostic biomarkers in elderly patients with treatment -resistant depression [8]. The stimulation of the HPA axis and over secretion of cortisol contributes to neurodegeneration which is a significant risk for late life depression and cognitive decline [41].…”

“…In a sample of community-dwelling adults older than 60 in China (N=4103), for example, 9% were noted to have comorbid depression and anxiety [7]. And, treatment resistant depression has been reported in as many as 30% of older patients with depression in another sample from China [8].…”