Indoleamine 2,3-dioxygenase activation and depressive symptoms in patients with coronary artery disease Walter Swardfager a,e , Nathan Herrmann a,f , Yekta Dowlati a,e , Paul I. Oh b,g , Alexander Kiss d , Scott E. Walker c , Krista L. Lanctoˆt a,e,f,g, * a Neuropsychopharmacology Research Group, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada b Division of Clinical Pharmacology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada c Department of Pharmacy, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada d Department of Clinical Epidemiology, Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada e Department of Pharmacology/Toxicology, University of Toronto, Toronto, Ontario, Canada f Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada g Cardiac Rehabilitation and Secondary Prevention Program, Toronto Rehabilitation Institute, Toronto, Ontario, Canada Received 2 April 2009; received in revised form 14 May 2009; accepted 26 May 2009 Psychoneuroendocrinology (2009) 34, 1560—1566 KEYWORDS Coronary artery disease; Kynurenine; Depression; Inflammation; Indoleamine 2,3- dioxygenase; Peak VO 2 Summary 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, anthropo- metric 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 (b = .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- * Corresponding author at: Neuropsychopharmacology Research Group, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Suite FG05, Toronto, Ontario, Canada M4N 3M5. Tel.: +1 416 480 6100x2241; fax: +1 416 480 6022. E-mail address: krista.lanctot@sunnybrook.ca (K.L. Lancto ˆt). available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/psyneuen 0306-4530/$ — see front matter # 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.psyneuen.2009.05.019