Indoleamine 2,3-dioxygenase activation and depressive symptoms in patients with coronary artery disease

An increase in immune-stimulated synthesis of kynurenine from tryptophan by indoleamine 2,3-dioxygenase (IDO) has been observed in patients with coronary artery disease (CAD). However, neuropsychiatric correlates of IDO activation remain unexplored. We hypothesize that IDO activation, as measured by the kynurenine to tryptophan (K/T) ratio, is associated with depressive symptoms in those with CAD. This cross-sectional study recruited subjects with CAD (n=95) from a cardiac rehabilitation facility. Demographic, anthropometric and cardiac data were obtained by chart review. Patients using an antidepressant were excluded. The presence of a major depressive episode or minor depression was assessed using a structured clinical interview for depression based on Diagnostic and Statistical Manual 4th edition criteria. The Center for Epidemiological Studies-Depression Scale (CES-D) was used to quantify depressive symptoms. A standardized exercise stress test was used to assess cardiopulmonary fitness as summarized using the peak volume of oxygen consumption (Peak VO(2)). Kynurenine and tryptophan were assayed from fasting plasma samples to obtain the K/T ratio. Higher K/T ratios were significantly associated with higher CES-D scores (beta=.322, p=.002) in a linear regression controlling for time since most recent acute coronary syndrome (tACS), age and sex. Twenty-four patients met criteria for depression (16 major depression; 8 minor depression). There was a trend towards higher K/T ratios in depressed vs. non-depressed patients (45.6+/-20.0 micromol/mmol vs. 38.5+/-15.7 micromol/mmol, F=3.778, p=.055) when controlling for age, sex and tACS. Activation of IDO is associated with the severity of depressive symptoms among patients with CAD.