Neuroinflammation in bipolar disorder - A [(11)C]-(R)-PK11195 positron emission tomography study

Brain Behav Immun. 2014 Aug:40:219-25. doi: 10.1016/j.bbi.2014.03.016. Epub 2014 Apr 3.

Abstract

Background: The "monocyte-T-cell theory of mood disorders" regards neuroinflammation, i.e. marked activation of microglia, as a driving force in bipolar disorder. Microglia activation can be visualized in vivo using [(11)C]-(R)-PK11195 PET. Indirect evidence suggests the hippocampus as a potential focus of neuroinflammation in bipolar disorder. We aim to determine if there is increased [(11)C]-(R)-PK11195 binding to activated microglia in the hippocampus of patients with bipolar I disorder when compared to healthy controls.

Material and methods: Fourteen patients with bipolar I disorder and eleven healthy controls were included in the analyses. Dynamic 60-min PET scans were acquired after the injection of [(11)C]-(R)-PK11195. All subjects underwent psychiatric interviews as well as an MRI scan, which was used for anatomic co-registration in the data analysis. The data from the PET scans was analyzed with a two-tissue-compartment model to calculate the binding potential, using the metabolite-corrected plasma and blood curve as input.

Results: A significantly increased [(11)C]-(R)-PK11195 binding potential, which is indicative of neuroinflammation, was found in the right hippocampus of the patients when compared to the healthy controls (1.66 (CI 1.45-1.91) versus 1.33 (CI 1.16-1.53); p=0.033, respectively). Although the same trend was observed in the left hippocampus, this difference was not statistically significant.

Conclusion: This study is the first to demonstrate the presence of focal neuroinflammation in the right hippocampus in bipolar I disorder.

Keywords: Bipolar disorder; Microglia; Neuroinflammation; PET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bipolar Disorder / diagnostic imaging
  • Bipolar Disorder / immunology*
  • Carbon Radioisotopes
  • Encephalitis / diagnostic imaging
  • Encephalitis / immunology*
  • Female
  • Hippocampus / diagnostic imaging
  • Hippocampus / immunology*
  • Humans
  • Isoquinolines
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Young Adult

Substances

  • Carbon Radioisotopes
  • Isoquinolines
  • PK 11195