Original ArticleSustained 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
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)
- et al.
Thematic review series: The immune system and atherogenesisLipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease?
J Lipid Res
(2005) - et al.
Discriminative value of serum amyloid A and other acute-phase proteins for coronary heart disease
Atherosclerosis
(2002) - et al.
Cytokine production and treatment response in major depressive disorder
Neuropsychopharmacology
(2000) - et al.
Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression
Cytokine
(1997) - et al.
Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression
J Affect Disord
(1995) - et al.
Clinical depression and inflammatory risk markers for coronary heart disease
Am J Cardiol
(2002) - et al.
C-reactive protein, inflammation, and coronary risk
Med Clin North Am
(2000) - et al.
Serum amyloid A predicts early mortality in acute coronary syndromes: A TIMI 11A substudy
J Am Coll Cardiol
(2000) - et al.
Inflammatory markers and depressed mood in older persons: results from the health, aging, and body composition study
Biol Psychiatry
(2003) Peroxisome proliferator-activated receptors as therapeutic targets in inflammation
J Am Coll Cardiol
(2003)
Sex differences in the relation of body composition to markers of inflammation
Atherosclerosis
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
Blood levels of cytokines in elderly patients with major depressive disorder
Acta Psychiatr Scand
C-Reactive protein, serum amyloid A protein, and coronary events
Circulation
Acute-phase proteins and other systemic responses to inflammation
N Engl J Med
Anti-inflammatory effects of statins: clinical evidence and basic mechanisms
Nat Rev Drug Discov
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
Cited by (97)
Immune-inflammatory markers of response to repetitive transcranial magnetic stimulation in depression: A scoping review
2024, Asian Journal of PsychiatryDoes inflammation mediate the effects of depression on heart disease? That may depend on the symptoms
2022, Journal of Psychosomatic ResearchElevated inflammatory markers in women with remitted major depressive disorder and the role of early life maltreatment
2021, Brain, Behavior, and ImmunityCitation 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.
Proinflammatory mediators and their associations with medication and comorbid traits in children and adults with ADHD
2020, European NeuropsychopharmacologyToll-Like Receptor Signaling in Depression
2020, PsychoneuroendocrinologyCitation 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.
Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls
2020, Brain, Behavior, and Immunity