Inflammatory cytokines, cortisol, and anhedonia in patients with treatment-resistant depression after consecutive infusions of low-dose esketamine

Abstract

Anhedonia, defined as a significant loss of interest or pleasure, is one of the core symptoms of treatment- resistant depression (TRD) and is often associated with poor prognosis. This article primarily investigates the changes in anhedonia symptoms, inflammatory markers, and cortisol levels in TRD patients after low-dose esketamine treatments. A total of sixty patients with TRD were enrolled in the clinical study of esketamine. We primarily assessed the severity of depressive symptoms and anhedonia using the Hamilton Rating Scale for Depression (HAMD) and the Snaith-Hamilton Pleasure Scal(SHAPS), respectively, before esketamine treatment and within 24 h after each treatment. Blood specimens were collected before the first treatment and within 1 h after the sixth treatment, measuring the levels of cortisol, interleukin-6(IL-6), interleukin-4(IL-4), and tumor necrosis factor-alpha(TNF-α) in plasma. We found that after six consecutive infusions of low-dose esketamine, patients' depressive symptoms and anhedonia showed improvement. After six treatments, plasma levels of cortisol, IL-6, and TNF-α decreased in patients with TRD, while the anti-inflammatory cytokine IL-4 increased. Multiple linear regression analysis revealed that baseline cortisol levels were correlated with anhedonia, while inflammatory factors showed no significant correlation. Add-on esketamine appears to be a good choice for the treament of the anhedonia in TRD. It has also shown promising effects on altering inflammatory markers in patients with TRD. Moreover, elevated plasma cortisol levels may serve as a potential biomarker for anhedonia in patients with TRD.

Keywords: Anhedonia; Cortisol; Esketamine; Inflammatory cytokines.