Association of Major Depressive Disorder with Serum Myeloperoxidase and Other Markers of Inflammation

A Twin Study

Viola Vaccarino, Marie Luise Brennan, Andrew H. Miller, J. Douglas Bremner, James C. Ritchie, Frauke Lindau, Emir Veledar, Shaoyong Su, Nancy V. Murrah, Linda Jones, Farhan Jawed, Jun Dai, Jack Goldberg, Stanley L. Hazen

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)476-483
Number of pages8
JournalBiological Psychiatry
Volume64
Issue number6
DOIs
StatePublished - Sep 15 2008
Externally publishedYes

Fingerprint

Twin Studies
Major Depressive Disorder
Peroxidase
Inflammation
Serum
Biomarkers
Monozygotic Twins
Tumor Necrosis Factor Receptors
Leukocyte Count
Diagnostic and Statistical Manual of Mental Disorders
C-Reactive Protein
Fibrinogen
Coronary Disease
Siblings
Interleukin-6
Leukocytes
Tumor Necrosis Factor-alpha

Keywords

  • Biomarkers
  • cardiovascular disease
  • depression
  • genetic factors
  • inflammation
  • twins

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Vaccarino, V., Brennan, M. L., Miller, A. H., Bremner, J. D., Ritchie, J. C., Lindau, F., ... Hazen, S. L. (2008). Association of Major Depressive Disorder with Serum Myeloperoxidase and Other Markers of Inflammation: A Twin Study. Biological Psychiatry, 64(6), 476-483. https://doi.org/10.1016/j.biopsych.2008.04.023

Association of Major Depressive Disorder with Serum Myeloperoxidase and Other Markers of Inflammation : A Twin Study. / Vaccarino, Viola; Brennan, Marie Luise; Miller, Andrew H.; Bremner, J. Douglas; Ritchie, James C.; Lindau, Frauke; Veledar, Emir; Su, Shaoyong; Murrah, Nancy V.; Jones, Linda; Jawed, Farhan; Dai, Jun; Goldberg, Jack; Hazen, Stanley L.

In: Biological Psychiatry, Vol. 64, No. 6, 15.09.2008, p. 476-483.

Research output: Contribution to journalArticle

Vaccarino, V, Brennan, ML, Miller, AH, Bremner, JD, Ritchie, JC, Lindau, F, Veledar, E, Su, S, Murrah, NV, Jones, L, Jawed, F, Dai, J, Goldberg, J & Hazen, SL 2008, 'Association of Major Depressive Disorder with Serum Myeloperoxidase and Other Markers of Inflammation: A Twin Study', Biological Psychiatry, vol. 64, no. 6, pp. 476-483. https://doi.org/10.1016/j.biopsych.2008.04.023
Vaccarino, Viola ; Brennan, Marie Luise ; Miller, Andrew H. ; Bremner, J. Douglas ; Ritchie, James C. ; Lindau, Frauke ; Veledar, Emir ; Su, Shaoyong ; Murrah, Nancy V. ; Jones, Linda ; Jawed, Farhan ; Dai, Jun ; Goldberg, Jack ; Hazen, Stanley L. / Association of Major Depressive Disorder with Serum Myeloperoxidase and Other Markers of Inflammation : A Twin Study. In: Biological Psychiatry. 2008 ; Vol. 64, No. 6. pp. 476-483.
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abstract = "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.",
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AU - Vaccarino, Viola

AU - Brennan, Marie Luise

AU - Miller, Andrew H.

AU - Bremner, J. Douglas

AU - Ritchie, James C.

AU - Lindau, Frauke

AU - Veledar, Emir

AU - Su, Shaoyong

AU - Murrah, Nancy V.

AU - Jones, Linda

AU - Jawed, Farhan

AU - Dai, Jun

AU - Goldberg, Jack

AU - Hazen, Stanley L.

PY - 2008/9/15

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N2 - 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.

AB - 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.

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