Elsevier

Biological Psychiatry

Volume 64, Issue 6, 15 September 2008, Pages 476-483
Biological Psychiatry

Archival Report
Association of Major Depressive Disorder with Serum Myeloperoxidase and Other Markers of Inflammation: A Twin Study

https://doi.org/10.1016/j.biopsych.2008.04.023Get rights and content

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.

Section snippets

Subjects

The Twins Heart Study (THS) is an investigation of psychological, behavioral, and biological risk factors for subclinical cardiovascular disease using twins. Twins were selected from the Vietnam Era Twin (VET) Registry (26), which includes 7369 middle-aged male-male twin pairs both of whom served in the United States military during the time of the Vietnam War.

The Twins Heart Study included 93 monozygotic and 87 dizygotic twin pairs who were born between 1946 and 1956. Zygosity information was

Results

Of the 180 THS twin pairs, we excluded 1 pair because of missing MPO data and another pair because of implausible TNF-α values. Of the remaining 178 pairs, 67 pairs were discordant for lifetime history of MDD and 111 were not. The majority of twins with MDD were in remission, with only eight subjects meeting DMS-IV criteria for a current major depressive episode and 77% having had the last depressive episode >1 year before examination.

Both in the entire population of twins and within the

Discussion

We found that MDD is associated with higher levels of inflammation and that this association is particularly robust for MPO, an inflammatory biomarker that was never studied before in relation to depression. However, we also found evidence for genetic confounding in this association. Our results are consistent with the hypothesis that there is a common genetic substrate linking MDD and inflammation, suggesting that these two phenotypes share a common pathophysiological mechanism.

Limitations

Our study is cross-sectional, thus limited in the ability to discern the temporal order between MDD and inflammation. However, based on our results, the covariation of these two phenotypes may mostly be due to a common genetic precursor rather than a cause-effect relationship. Another limitation is that few twins met the criteria for a current major depressive episode, preventing us from examining the data in relation to current versus past depression. However, there was no relationship between

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