13. Inflammation as target in treatment of depression in CHD patients: Evidence from an in vitro study

Abstract

Inflammation has been recognized as a common link between coronary heart disease (CHD) and depression. One of the important biological factors that regulate inflammation is the glucocorticoid receptor (GR). We investigated inflammatory markers and GR function in CHD patients with ( n = 28) and without ( n = 55) depression. Serum CRP and plasma VEGF were measured using ELISA. IL-6 gene expression was measured via qPCR. GR sensitivity was evaluated by dexamethasone inhibition of lipopolysaccharide-stimulated IL-6 levels. Compared to CHD non-depressed individuals, CHD patients with depression showed higher serum levels of CRP (5.20 vs 3.34 mg/l, p = 0.030), higher gene expression of IL-6 (2.8-fold increase, p = 0.003), and higher plasma levels of VEGF (173.13 vs 94.24 pg/ml, p = 0.028). The depressed group exhibited reduced GR function (IC50: 8.12 vs 7.59[M], p = 0.0031) which was associated with the severity of depression ( r = 0.505, p = 0.006). CHD depressed subjects showed an increased in GR sensitivity by the in vitro effect of clomipramine (IC50: 7.54 vs 7.81[M], p = 0.084), citalopram (IC50: 7.57 vs 8.06[M], p = 0.014), and the omega-3 fatty acid EPA (IC50: 7.43 vs 8.61[M], p = 0.006). Our results show that CHD patients with depression exhibited GR resistance in vitro and elevated inflammatory response. This study provides evidence of improvement of GR sensitivity in vitro in response to the effect of antidepressants and omega-3 fatty acids that may lead to a more effective response to the anti-inflammatory and immunosuppressive activities of glucocorticoids.