The acute-phase mediator serum amyloid A is associated with symptoms of depression and fatigue

Acta Psychiatr Scand. 2017 May;135(5):409-418. doi: 10.1111/acps.12730. Epub 2017 Apr 4.


Objective: Establish whether inflammatory biomarkers-serum amyloid A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)-are related to key symptoms of depression, including anxiety and fatigue, in a cross-sectional, out-patient setting to identify biomarkers that reflect psychiatric symptomatology in a naturalistic, real-life population.

Methods: We measured SAA, CRP, IL-6, and TNF-α in plasma samples from 89 adult psychiatric out-patients by multiplex, high-sensitivity electrochemiluminescent assays. Psychiatric symptoms were evaluated using the Hamilton Depression Rating Scale (HAMD-17), the Patient Health Questionnaire (PHQ-9), and the Center for Epidemiological Studies Depression Scale (CES-D).

Results: Plasma SAA was most robustly associated with depressive symptoms across diagnostic boundaries in this cohort of out-patients. Elevated SAA was significantly associated with higher total scores on the HAMD-17 scale and correlated with multiple scale items that rated symptoms of fatigue and depressed mood, but not with anxiety-related items.

Conclusions: SAA might constitute a cross-diagnostic marker indicative of depressed mood and fatigue in a naturalistic patient setting. Because SAA activates Toll-like receptors 2 and 4, present on macrophages and glial cells, its association with depression severity could also implicate this inflammatory mediator in the pathogenesis of mood disorders.

Keywords: C-reactive protein; biomarker; inflammation; interleukin-6; mood disorders.

MeSH terms

  • Adult
  • Aged
  • C-Reactive Protein / metabolism
  • Cross-Sectional Studies
  • Depression / metabolism*
  • Fatigue / metabolism*
  • Female
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Serum Amyloid A Protein / metabolism*
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult


  • IL6 protein, human
  • Interleukin-6
  • Serum Amyloid A Protein
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein