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 [11C]-(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 [11C]-(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 [11C]-(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 [11C]-(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.

Bipolar disorder, Microglia, Neuroinflammation, PET,
Brain, Behavior, and Immunity
This work was funded by the European Commission 7th Framework Programme; grant id fp7/222963 - Early diagnosis, treatment and prevention of mood disorders targetting the activated inflammatory response system (MOODINFLAME)
Department of Immunology

Haarman, B.C.M, Riemersma-Van der Lek, R.F, de Groot, J.C, Ruhé, H.G, Klein, H.C, Zandstra, T.E, … Doorduin, J. (2014). Neuroinflammation in bipolar disorder - A [11C]-(R)-PK11195 positron emission tomography study. Brain, Behavior, and Immunity, 40, 219–225. doi:10.1016/j.bbi.2014.03.016