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


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.


CONCLUSIONS
This study is the first to demonstrate the presence of focal neuroinflammation in the right hippocampus in bipolar I disorder.
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands. Electronic address: b.c.m.haarman@umcg.nl.
Bartholomeus C M Benno
BC
Haarman
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
Rixt F
RF
Riemersma-Van der Lek
University of Groningen, University Medical Center Groningen, Department of Radiology, Groningen, The Netherlands.
Jan Cees
JC
de Groot
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
Henricus G Eric
HG
Ruhé
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen, The Netherlands.
Hans C
HC
Klein
University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen, The Netherlands.
Tjitske E
TE
Zandstra
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of General Practice, Groningen, The Netherlands.
Huibert
H
Burger
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
Robert A
RA
Schoevers
University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen, The Netherlands.
Erik F J
EF
de Vries
Erasmus MC, Department of Immunology, Rotterdam, The Netherlands.
Hemmo A
HA
Drexhage
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
Willem A
WA
Nolen
University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen, The Netherlands.
Janine
J
Doorduin
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000276:immunology*; D002250:Carbon Radioisotopes; D004660:Encephalitis / Q000000981:diagnostic imaging / Q000276:immunology*; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000276:immunology*; D006801:Humans; D007546:Isoquinolines; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D055815:Young Adult
D002250:Carbon Radioisotopes; D007546:Isoquinolines; C037850:PK 11195
Bipolar disorder; Microglia; Neuroinflammation; PET