Depressive symptoms are associated with reduced neutrophil function in hip fracture patients

Abstract

Hip fracture is a common trauma in older adults with a high incidence of depression, which relates to poorer prognosis including increased risk of infection. Ageing is accompanied by reduced immunity, termed immunesenescence, resulting in increased susceptibility to infection. We examined whether physical trauma (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system that might contribute to poor outcomes after injury. Neutrophil function was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age-matched controls (28 female). Thirty eight fracture patients had depressive symptoms at 6 weeks. No difference in neutrophil phagocytosis of Escherichia coli was observed between controls and hip fracture patients, but superoxide production was significantly reduced in hip fracture patients with depressive symptoms compared with patients without symptoms (p=.001) or controls (p=.004) at 6 weeks. Superoxide production improved 6 months following fracture to the level seen in controls. We detected elevated serum cortisol, reduced dehydroepiandrosterone sulphate (DHEAS) and an increased cortisol:DHEAS ratio in fracture patients with depressive symptoms compared with patients without depressive symptoms or controls at 6 weeks and 6 months after injury. Serum IL6, TNFα and IL10 were higher among patients with depressive symptoms at 6 weeks. The cortisol:DHEAS ratio and IL6 levels related to depressive symptom scores but not to neutrophil function. In conclusion, depressive symptoms related to poorer neutrophil function after hip fracture, but this was not driven by changes in stress hormone or cytokine levels.

Keywords: Ageing; Cortisol; Dehydroepiandrosterone; Depressive symptoms; Hip fracture; Neutrophil function.

Fig. 1

Recruitment and attrition in the study.

Fig. 2

Neutrophil superoxide production on stimulation with E. coli in hip fracture patients with and without depressive symptoms versus healthy controls. (a) Neutrophil superoxide production (MFI) for hip fracture patients with (n = 35), or without depressive symptoms (n = 60) and healthy controls (n = 32). The solid bar represents the mean value and ^∗∗indicates p < .005. (b) Correlation between GDS scores and neutrophil superoxide generation.

Fig. 3

Stress hormone levels in hip fracture patients with and without depressive symptoms versus healthy controls. (a) cortisol: DHEAS ratio in hip fracture patients with (n = 35), or without depressive symptoms (n = 54) and healthy controls (n = 32). Data are mean ± SEM and for ^∗p < .05, ^∗∗p < .01 and ^∗∗∗p < .001.

Fig. 4

Serum cytokine levels in hip fracture patients with and without depressive symptoms versus healthy controls. (a) Mean serum IL6 levels for hip fracture patients with (n = 29), or without depressive symptoms (n = 37) and healthy controls (n = 28). (b) Mean serum TNFα levels for hip fracture patients with (n = 20), or without depressive symptoms (n = 21) and healthy controls (n = 23). (c) Mean serum IL10 levels for hip fracture patients with (n = 20), or without depressive symptoms (n = 21) and healthy controls (n = 23). Data are mean ± SEM and for ^∗p < .05, ^∗∗p < .01 and ^∗∗∗p < .001.

Fig. 5

Neutrophil superoxide generation and cortisol:DHEAS ratio in hip fracture patients 6 weeks and six months after surgery. Mean neutrophil superoxide generation for hip fracture patients with (n = 26) or without depressive symptoms (n = 39) at 6 weeks and 6 months post injury. Data are mean ± SEM and ^∗indicates p < .05.