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      Speaker 1: John O’Brien, UK

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          Title: Neuroinflammatory changes in late life depression: the NIMROD study Abstract Introduction: Late life depression is known to be associated with specific clinical features, such as cognitive impairments, to have a poor outcome and to be a risk factor for future dementia. Vascular factors have been implicated in aetiology, but neuroinflammation has not been well studied despite being a highly plausible mechanism and potentially tractable target. In our previous work we have shown an increase in inflammatory cytokines in the blood in older depressed subjects, In the current study we aimed to show whether we could demonstrate an increase in central (brain) inflammation in vivo using PET imaging. Methods: Within the Cambridge Neuroimaging of Inflammation in MemoRy and Other Disorders (NIMROD) study we have recruited 5 older depressed subjects who had met DSM-IV criteria for major depression and 13 controls. Subjects had full clinical and cognitive assessment and venipuncture for CRP measurement. Brain imaging was performed with PET for 75 minutes following bolus iv injection of [11C]PK11195 (500MBq) and multi-modal 3T MR imaging was also undertaken. Using regional reference tissue modelling of the dynamic PET data corrected for CSF contamination, non-displaceable binding potential (BPND) was estimated using region of interest analysis. Results: Depressed subjects (Dep) and controls (Con) did not differ in age, sex ratio, education or global cognition (MMSE score) but had significantly higher blood CRP levels than controls (mean (SD): Dep 6.4 (5.1); Con 1.0 (1.2); p<0.05). Though largely recovered from their depression at time of imaging, depressed subjects had significantly raised [11C]PK11195 BPND compared to controls in several regions (for example, anterior cingulate mean (SD): Dep: 0.118 (0.061); Con: 0.025 (0.067); p = 0.025). Conclusions: We found evidence of both central and peripheral inflammation in older subjects with depression, with changes in areas including the anterior cingulate, known to play a key role in the regulation of mood. Neuroinflammation may be an important mechanism in late life depression and merits further investigation as a potential target for novel therapeutics in a condition which responds poorly to conventional antidepressant therapy.

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          Author and article information

          Journal
          Int J Neuropsychopharmacol
          Int. J. Neuropsychopharmacol
          ijnp
          International Journal of Neuropsychopharmacology
          Oxford University Press (US )
          1461-1457
          1469-5111
          June 2016
          27 May 2016
          : 19
          : Suppl 1
          : 44-45
          Affiliations
          [1 ]Department of Psychiatry, University of Cambridge, UK
          [2 ]Wolfson Brain Imaging Centre, University of Cambridge, UK
          [3 ]Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
          [4 ]Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, UK
          [5 ]Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
          Article
          pyw042.118
          10.1093/ijnp/pyw042.118
          5616594
          e793c362-9ee1-4a80-a671-43a7c9483d6d
          © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
          History
          Page count
          Pages: 2
          Categories
          Abstracts
          Speaker Abstracts

          Pharmacology & Pharmaceutical medicine
          Pharmacology & Pharmaceutical medicine

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