Association of major depressive disorder with serum myeloperoxidase and other markers of inflammation: a twin study.
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)-alpha, the TNF-alpha 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.
Vaccarino
Viola
V
Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30306, USA. viola.vaccarino@emory.edu
Brennan
Marie-Luise
ML
Miller
Andrew H
AH
Bremner
J Douglas
JD
Ritchie
James C
JC
Lindau
Frauke
F
Veledar
Emir
E
Su
Shaoyong
S
Murrah
Nancy V
NV
Jones
Linda
L
Jawed
Farhan
F
Dai
Jun
J
Goldberg
Jack
J
Hazen
Stanley L
SL
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003327:Coronary Disease / Q000453:epidemiology; D003865:Major Depressive Disorder / Q000097:blood* / Q000453:epidemiology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005340:Fibrinogen / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007377:Interleukin-3 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000097:blood*; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000097:blood; D011994:Recombinant Proteins; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014427:Twins / Q000235:genetics
D015415:Biomarkers; D007377:Interleukin-3; D015850:Interleukin-6; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C404145:myelopoietin; D016179:Granulocyte Colony-Stimulating Factor; D005340:Fibrinogen; D002097:C-Reactive Protein; D009195:Peroxidase