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Psychosomatic Medicine 70:953-959 (2008)
© 2008 American Psychosomatic Society

ORIGINAL ARTICLES

Relationship of Genetic Variability and Depressive Symptoms to Adverse Events After Coronary Artery Bypass Graft Surgery

Barbara Phillips-Bute, PhD, Joseph P. Mathew, MD, James A. Blumenthal, PhD, Richard W. Morris, PhD, Mihai V. Podgoreanu, MD, Michael Smith, MS, Mark Stafford-Smith, MD, Hilary P. Grocott, MD, Debra A. Schwinn, MD, Mark F. Newman, MD for the Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team1

From the Departments of Anesthesiology (B.P.-B., J.P.M., R.W.M., M.V.P., M.S., M.S.-S., H.P.G., D.A.S., M.F.N.) and Psychiatry and Behavioral Sciences (B.P.-B., J.A.B.), Duke University Medical Center, Durham, North Carolina.

Address correspondence and reprint requests to Barbara Phillips-Bute, Department of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710. E-mail: phill016{at}mc.duke.edu

Objective: To assess genetic variability in two serotonin-related gene polymorphisms (MAOA-uVNTR and 5HTTLPR) and their relationships to depression and adverse cardiac events in a sample of patients undergoing coronary artery bypass surgery.

Methods: A total of 427 coronary artery bypass graft (CABG) patients were genotyped for two polymorphisms and assessed for depressive symptoms at three time points, in accordance with the Center for Epidemiological Studies-Depression (CES-D): preoperative baseline; 6 months postoperative; and 1 year postoperative. Logistic regression was used to assess the association between depressive symptoms (CES-D = >16), genotype differences, and cardiac events. Because MAOA-uVNTR is sex-linked, males and females were analyzed separately for this polymorphism; sexes were combined for the 5HTTLPR analysis.

Results: Depressed patients were more likely than nondepressed patients to have a new cardiac event within 2 years of surgery (p < .0001); depressed patients who carry the long (L) allele of the 5HTTLPR polymorphism were more likely than the short/short (S/S carriers to have an event (p = .0002). Genetic associations with 6-month and 1-year postoperative depressive symptoms do not survive adjustment for baseline depressive symptoms.

Conclusions: A serotonin-related gene polymorphism—5HTTLPR—was associated with adverse cardiac events post CABG, in combination with depressive symptoms. Because depressed patients with the L allele of the 5HTTLPR polymorphism were more likely to have an event compared with the S/S carriers, combining genetic and psychiatric profiling may prove useful in identifying patients at the highest risk for adverse outcomes post CABG.

Key Words: depression • CABG surgery • serotonin • genetic variability • monoamine oxidase-A • serotonin transporter gene

Abbreviations: CABG = coronary artery bypass graft; CES-D = Center for Epidemiological Studies-Depression; PEGASUS = Perioperative Genetics and Safety Outcomes Study; MI = myocardial infarction; MAOA = monoamine oxidase A; VNTR = variable number of tandem repeats; L = long; L/L = long/long; S/S = short/short.






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