Association of Major Depressive Disorder with Serum Myeloperoxidase and Other Markers of Inflammation: A Twin Study
Received 1 January 2008; received in revised form 15 April 2008; accepted 15 April 2008. published online 03 June 2008.
Background
Major depressive disorder (MDD) has been linked to inflammation, but this association may be due to common precursors to both depression and inflammation. Myeloperoxidase (MPO) is an inflammatory enzyme produced by activated leukocytes that predicts risk of coronary heart disease. We sought to examine whether MPO and other markers of inflammation are associated with MDD and whether the association is confounded by genetic or other shared familial factors.
Methods
We examined 178 monozygotic and dizygotic middle-aged male twin pairs. We assessed MDD with the Structured Clinical Interview for DSM-IV. Blood markers of inflammation included MPO, interleukin-6, white blood cell count, C-reactive protein, tumor necrosis factor (TNF)-α, the TNF-α soluble receptor II, and fibrinogen. Analyses were conducted in the overall sample and among 67 twin pairs discordant for MDD using mixed effects regression.
Results
Twins with a history of MDD had 32% higher levels of MPO (p < .0001); this difference persisted after adjusting for other risk factors. Among dizygotic MDD-discordant twin pairs, twins with MDD had 77% higher MPO than their brothers without MDD, after adjusting for other factors (p < .0001). In contrast, no significant association was found in monozygotic twins (p = .13). Similar, but weaker, associations were found between MDD and other inflammatory biomarkers.
Conclusions
Myeloperoxidase is a useful biomarker of immune activation in MDD. However, the association between inflammation and MDD is largely due to common genetic liability. Our results are consistent with the hypothesis that genes promoting inflammation are involved in the pathogenesis of MDD.
aDepartment of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia
bDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
cDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia
dDepartment of Pathology and Laboratory Medicine, Emory University Hospital, Emory University School of Medicine, Atlanta, Georgia
eDepartment of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio
fDepartment of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
gCenter for Cardiovascular Diagnostics and Prevention, Cleveland Clinic Foundation, Cleveland, Ohio
hVietnam Era Twin Registry and the University of Washington School of Public Health and Community Medicine, Seattle, Washington
Address reprint requests to Viola Vaccarino, M.D., Ph.D., Emory University School of Medicine, Department of Medicine, Division of Cardiology, 1256 Briarcliff Road NE, Suite-1 North, Atlanta, GA 30306
ABSTRACT