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.
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.
Authors: Zeneng Wang; Stephen J Nicholls; E Rene Rodriguez; Outi Kummu; Sohvi Hörkkö; John Barnard; Wanda F Reynolds; Eric J Topol; Joseph A DiDonato; Stanley L Hazen Journal: Nat Med Date: 2007-09-09 Impact factor: 53.440
Authors: Moniek P M de Maat; Else Marie Bladbjerg; Jacob von Bornemann Hjelmborg; Lise Bathum; Jørgen Jespersen; Kaare Christensen Journal: Arterioscler Thromb Vasc Biol Date: 2004-09-02 Impact factor: 8.311
Authors: Micaela Santos; Enikö Kövari; Patrick R Hof; Gabriel Gold; Constantin Bouras; Panteleimon Giannakopoulos Journal: Brain Res Rev Date: 2009-09-08
Authors: Amit Jasvant Shah; Shaoyong Su; Emir Veledar; James Douglas Bremner; Felicia C Goldstein; Rachel Lampert; Jack Goldberg; Viola Vaccarino Journal: Psychosom Med Date: 2011-06-28 Impact factor: 4.312
Authors: Shaoyong Su; Andrew H Miller; Harold Snieder; J Douglas Bremner; James Ritchie; Carisa Maisano; Linda Jones; Nancy V Murrah; Jack Goldberg; Viola Vaccarino Journal: Psychosom Med Date: 2008-12-10 Impact factor: 4.312
Authors: Jinying Zhao; Mary J Roman; Richard B Devereux; Fawn Yeh; Ying Zhang; Karin Haack; Lyle G Best; Shelley A Cole; Elisa T Lee; Barbara V Howard Journal: Atherosclerosis Date: 2014-01-10 Impact factor: 5.162