Preliminary differences in peripheral immune markers and brain metabolites between fatigued and non-fatigued breast cancer survivors: a pilot study

Suzanna Maria Zick, Heather Zwickey, Lisa Wood, Bradley Foerster, Tohfa Khabir, Benjamin Wright, Eric Ichesco, Ananda Sen, Richard Edmund Harris

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Persistent cancer-related fatigue (PCRF) is one of the most troubling side-effects of breast cancer (BC) treatment. One explanatory model for PCRF is sickness behavior, which is a set of adaptive responses including sleepiness and depressed mood in reaction to an inflammatory trigger. Prior research has investigated differences in inflammatory cytokines between fatigued and non-fatigued BC survivors, but no study has examined differences in brain metabolites. Differences in inflammatory markers, and brain metabolites using proton magnetic resonance spectroscopy were evaluated within 16 fatigued and 13 non-fatigued BC survivors. Fatigued BC survivors had significantly higher ratios of two markers derived from brain metabolites; namely (a) creatine, normalized to total creatine (creatine + phosphocreatine (Cr/tCr)) ratio (P = 0.03) and (b) glutamate + glutamine (Glx) to N-acetyl-aspartate (NAA) ratio (P = 0.01) in the posterior insula compared to non-fatigued breast cancer survivor. Further, serum IL-6 was increased in fatigued women compared to non-fatigued women (P = 0.03), Using receiver operator curves (ROC) we determined that the posterior insula Glx/NAA ratio was the best predictor of fatigue with an overall area under the receiver operating characteristic curve (AUROC) of 79 %, with a sensitivity of 81 % and a specificity of 69 %. However, posterior insula Glx/NAA, Cr/tCr and serum IL-6 were not significantly correlated with one another implying the possibility of independent biological mechanisms for PCRF rather than an interrelated mechanism as represented by the sickness behavior model. This study provides novel preliminary evidence of several distinct neurobiological changes in the posterior insula associated with PCRF in BC survivors. Future, longitudinal studies are needed to explore these distinct biological phenomena where changes through time in peripheral immune markers and brain metabolites are examined to determine if they correlate with changes in fatigue.

Original languageEnglish (US)
Pages (from-to)506-516
Number of pages11
JournalBrain Imaging and Behavior
Issue number4
StatePublished - Nov 23 2014


  • Anterior cingulate
  • Anterior insula
  • Breast cancer survivors
  • C-reactive protein
  • Creatine
  • Cytokines
  • Glutamate
  • Magnetic resonance spectroscopy
  • Occipital cortex
  • Persistent fatigue
  • Posterior insula

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Cognitive Neuroscience
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Behavioral Neuroscience


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