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

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

Brain, behavior, and immunity (2014-04-08)
Bartholomeus C M Benno Haarman, Rixt F Riemersma-Van der Lek, Jan Cees de Groot, Henricus G Eric Ruhé, Hans C Klein, Tjitske E Zandstra, Huibert Burger, Robert A Schoevers, Erik F J de Vries, Hemmo A Drexhage, Willem A Nolen, Janine Doorduin
ABSTRACT

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

MATERIALS
Product Number
Brand
Product Description

Supelco
Lidocaine, Pharmaceutical Secondary Standard; Certified Reference Material
Lidocaine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Lidocaine, analytical standard
Sigma-Aldrich
Lidocaine, powder
USP
Lidocaine, United States Pharmacopeia (USP) Reference Standard