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

Highlight•There is increased [11C]-(R)-PK11195 binding in the right hippocampus in bipolar I disorder, consistent with the monocyte-T-cell theory of mood disorders.

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.