Elsevier

Biological Psychiatry

Volume 62, Issue 4, 15 August 2007, Pages 309-313
Biological Psychiatry

Original Article
Sustained Low-Grade Pro-inflammatory State in Unmedicated, Remitted Women with Major Depressive Disorder as Evidenced by Elevated Serum Levels of the Acute Phase Proteins C-reactive Protein and Serum Amyloid A

https://doi.org/10.1016/j.biopsych.2006.09.033Get rights and content

Background

Major depressive disorder (MDD) shows increased coronary artery disease (CAD) risk of unknown mechanism(s). MDD is more common in women than men; CAD diagnosis can be difficult in women. Elevations of the inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) predict increased CAD risk in populations; few data on these markers exist in MDD, particularly in remitted patients.

Methods

We measured fasting am serum CRP (high sensitivity, CRPhs) and SAA in 18 unmedicated, remitted women with MDD (mean age 41 ± (SD)12, body mass index (BMI) 25.2 ± 4.1 kg/m2) and 18 BMI-matched healthy control subjects (age 36 ± 10, BMI 25.3 ± 3.8 kg/m2) on 2 separate occasions, ≥ 6 days apart.

Results

Repeat SAA and CRPhs measurements strongly correlated across study days (SAA: r = .83, p < .001; CRPhs: r = .94, p < .001). Both SAA (5.30 ± 3.39 vs. 2.84 ± 1.87 mg/L, p < .005) and CRPhs (3.23 ± 3.17 vs. 1.12 ± 1.45 mg/L; p < .01) were significantly elevated in MDD women versus controls.

Conclusions

Elevated SAA and CRPhs in remitted, unmedicated women with MDD indicate a pro-inflammatory state unrelated to current depressive symptoms or pharmacotherapy. These findings suggest that inflammatory mechanisms may in part underlie findings of increased CAD risk in MDD.

Section snippets

Participants

Eighteen women (mean age 41 ± (SD) 12 years; mean body mass index [BMI] 25.2 ± 4.1 kg/m2) with MDD in remission after at least 2 prior episodes, and off psychotropic medications for ≥ 3 months, and 18 individually BMI-matched (within ± 2 kg/m2) healthy control subjects (age 36 ± 10 years; mean BMI 25.3 ± 3.8 kg/m2) were included in the study. Two of the MDD patients and 4 control subjects identified themselves as African-American; the remaining subjects were self-identified as Caucasian, of

Results

The mean age between subject groups did not differ significantly (paired ⊻t⊻ = 1.37, df = 17, p = .19). The differences in ethnic composition of the 2 groups did not differ significantly. The mean 24-item HDRS score was .76 ± .96 (mean ± SD; range: 0-4) in the MDD women, and .39 ± .5 (range: 0-2) in controls.

Within-subject correlations for SAA and CRPhs levels between the two sampling dates were robust (SAA: r = .83, p < .001; CRPhs: r = .94, p < .001). In addition, the absolute values of these

Discussion

Serum SAA was increased significantly and, on average, by over 86% in the group of remitted, unmedicated MDD women versus BMI-matched control subjects. Serum CRPhs was increased significantly and by an average of almost three-fold in these patients. The proportion of women at high risk for future CAD, on the basis of established cut-off values for SAA and CRP, was 4 times higher in MDD women than in controls. These differences were based on two separate determinations showing high test-retest

References (35)

  • B. Thorand et al.

    Sex differences in the relation of body composition to markers of inflammation

    Atherosclerosis

    (2006)
  • S. Alesci et al.

    Major Depression is associated with significant diurnal elevations in plasma IL-6 levels, a shift of its circadian rhythm, and loss of physiologic complexity in its secretion: Clinical implications

    J Clin Endocrinol Metab

    (2005)
  • F. Brambilla et al.

    Blood levels of cytokines in elderly patients with major depressive disorder

    Acta Psychiatr Scand

    (1998)
  • R.P. Choudhury et al.

    C-Reactive protein, serum amyloid A protein, and coronary events

    Circulation

    (1999)
  • C. Gabay et al.

    Acute-phase proteins and other systemic responses to inflammation

    N Engl J Med

    (1999)
  • M.K. Jain et al.

    Anti-inflammatory effects of statins: clinical evidence and basic mechanisms

    Nat Rev Drug Discov

    (2005)
  • B.D. Johnson et al.

    Serum amyloid A as a predictor of coronary artery disease and cardiovascular outcome in women: the National Heart, Lung, and Blood Institute-Sponsored Women’s Ischemia Syndrome Evaluation (WISE)

    Circulation

    (2004)
  • Cited by (97)

    • Elevated inflammatory markers in women with remitted major depressive disorder and the role of early life maltreatment

      2021, Brain, Behavior, and Immunity
      Citation Excerpt :

      Previous findings include a reduction in serum immunoglobulin A (IgA) levels (Gold et al., 2012), and elevated levels of interleukin-8 (IL-8) (Vogelzangs et al., 2016), tumor necrosis factor-α (TNF-α) (Narita et al., 2006), and serum amyloid A (SAA) (Kling et al., 2007). Results on CRP and IL-6 are currently limited and somewhat conflicting: Kling et al. (2007) found higher levels of CRP in n = 18 women with MDD in remission (rMDD) compared to healthy controls, but Frommberger et al. (1997) showed that IL-6 levels decreased after remission and were not significantly different from those of healthy controls in a sample of n = 12 MDD patients. Further research is therefore needed to clarify whether the elevation of CRP and IL-6 levels is not only observable in patients with acute depression but also after remission of MDD.

    • Toll-Like Receptor Signaling in Depression

      2020, Psychoneuroendocrinology
      Citation Excerpt :

      Several DAMPs, including HMGB1, RNA, and HSPs promote depressive-like behaviors in stress models of depression (Franklin et al., 2018). In human studies, increased peripheral concentrations of SAA, uric acid, and S100b have been reported in MDD (Kling et al., 2007; Rothermundt et al., 2001; Tao and Li, 2015; Tsai and Huang, 2016). Taken together, this suggest that DAMPs may contribute to sterile inflammation in MDD patients.

    View all citing articles on Scopus
    View full text