Bishop, C

Ciccarelli, O

Colasanti, A

Giannetti, P

Gunn, R

Guo, Q

Malik, O

Matthews, PM

Muraro, P

Newbould, RD

Nicholas, R

Onega, M

Owen, D

Piccini, P

Rabiner, EA

Wall, M

Young, AH

Multiple Sclerosis Journal

Spiral - Imperial College Digital Repository

 Abstract Preview - Step 3/4- print version -   Topic: 20. ImagingTitle: Hippocampal inflammation and depression in multiple sclerosis: integrating evidence fromTSPO PET and resting state fMRIAuthor(s): A. Colasanti1,2, Q. Guo3, P. Giannetti1, M. Wall3, R.D. Newbould3, C. Bishop3, M. Onega3, R.Nicholas4, O. Ciccarelli5, P. Muraro1, O. Malik4, D. Owen1, A.H. Young2, R. Gunn3, P. Piccini1, P.M.Matthews1, E.A. Rabiner3Institute(s): 1Imperial College London, Division of Brain Sciences, 2Institute of Psychiatry, Psychology &Neuroscience; King's College London, 3Imanova Ltd, 4Imperial College Healthcare NHS Trust,5Department of Neuroinflammation, UCL Institute of Neurology, London, United KingdomText: Depression is highly prevalent in patients with multiple sclerosis (MS) and is associated moregenerally with elevated inflammatory markers, suggesting common pathophysiologicalmechanisms. The hippocampus is implicated in the pathophysiology of depression and issusceptible to neuroinflammation in MS. We hypothesise that the high prevalence of depression inMS is a consequence of the chronic immune activation in the hippocampus.We characterized the relationship between depressive symptoms and hippocampal microglialactivation in MS patients using the 2nd generation TSPO radioligand [18F]-PBR111. To evaluatepathophysiological mechanisms, we explored the relationships between hippocampal inflammation,depressive symptoms and hippocampal functional connectivity as defined by resting state fMRI.11 patients with multiple sclerosis and 22 healthy controls were administered the Beck's DepressionInventory (BDI) and were genotyped for the SNP rs6971 of the TSPO gene, prior to PET and fMRIscanning. The Distribution Volume Ratio (DVR) of [18F]-PBR111 in the hippocampus was estimatedas an index of activated microglia density. For the analysis of functional connectivity, thehippocampus was used as the seed region. We compared [18F]-PBR111 uptake in thehippocampus of MS patients relative to healthy controls and examined the correlations between[18F]-PBR111 uptake, BDI scores, and hippocampal functional connectivities in patients with MS.[18F]-PBR111 DVR was higher in the hippocampus of MS patients relative to healthy controls(F=5.73; p=0.024) and in MS patients the hippocampal DVR was correlated with the intensity ofdepressive symptoms (r=0.86, p=0.006). The strength of hippocampal functional connectivity toprefrontal regions, including the subgenual cingulate, and parietal regions, such as posteriorcingulate and precuneus, correlated with both depressive symptoms and [18F]-PBR111 DVR (p<0.05 or z=2.3; cluster-corrected for multiple comparisons).Our results provide evidence that hippocampal microglial activation in MS impairs the brainfunctional connectivities in regions contributing to maintenance of a normal affective state. Theysuggest a rationale for the responsiveness of depression in some people with MS to effectivecontrol of brain inflammation.Disclosure: GSK contributed PET scanning time and operational support for the study.A.Colasanti was supported by a GSK/Wellcome Trust fellowship.R. Nicholas received honoraria or funding from Bayer, Biogen, Genzyme, Merck Serono, Novartis,Roche, Teva.O.Ciccarelli receives grant support from the Multiple Sclerosis Society of Great Britain and NorthernIreland, the Department of Health Comprehensive Biomedical Centre, the ISCRT and the EPSRC;she serves as a consultant for Novartis, Biogen and GE and payments are made to UCL Institute ofNeurology.P.A.Muraro declares honoraria for speaking and travel support from Merck Serono, Biogen, Bayer,and Novartis.O. Malik received honoraria from Biogen, Scheering, Teva and Novartis for lectures and advisorypanels and received travel grants for conferences from Biogen and Novartis.A.H.Young declares paid lectures and advisory boards for all major pharmaceutical companies withdrugs used in affective and related disorders, and no share holdings in pharmaceutical companies.R.Gunn is a consultant for GSK, Abbvie, UCB and ITI.P.Piccini has received ´ad hoc' consultancies from TEVA, Michael J Fox Foundation (US), CHDI(US), Parkinson UK, Network European CNS Transplantation and Restoration (NECTAR),Evaluation Committee of PRTS of the French National Research Agency, Canada Research ChairsProgram, France Parkinson «Grand Appel d'Offres». All honoraria paid for these consultanciesgoes to Imperial College London.P.M.Matthews holds stock in GSK, has received research funds from Biogen and GSK, andconsultancy/speaker fees from IXICO, GSK, Biogen, Novartis and Adelphi Communications. Allhonoraria paid for these consultancies goes to Imperial College London.E.A.Rabiner holds stock in GSK, and consultancy/speaker fees from Lightlake Therapeutics,Gedeon Richter, AbbVie, BioTie.Q.Guo, P. Giannetti, M.Wall, R.D. Newbould, C. Bishop, M. Onega, D.Owen, have nothing todisclose.Travel Grant /Young Scientific Investigator'sSessions:I will not apply for Travel Grant or Young Scientific Investigator's Sessions 31st Congress of the European Committee for Treatment and ... http://www.abstractserver.com/ectrims2015/absmgm/printpre...1 of 2 19/05/2015 18:36Preferred PresentationType: Oral or poster presentation Conference: 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis · Abstract: A-733-0022-01844 ·Status: Submitted    31st Congress of the European Committee for Treatment and ... http://www.abstractserver.com/ectrims2015/absmgm/printpre...2 of 2 19/05/2015 18:36

English

Hippocampal inflammation and depression in multiple sclerosis: integrating evidence from TSPO PET and resting state fMRI

Hippocampal inflammation and depression in multiple sclerosis: integrating evidence from TSPO PET and resting state fMRI

Abstract

Similar works

Full text

Available Versions

Spiral - Imperial College Digital Repository