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Evidence of upregulation of the cholinergic anti-inflammatory pathway in late-life depression

Pomara, N, Bruno, D, Reichert Plaska, C, Pillai, A, Ramos-Cejudo, J, Osorio, R, Imbimbo, B, Heslegrave, A, Zetterberg, H and Blennow, K (2021) Evidence of upregulation of the cholinergic anti-inflammatory pathway in late-life depression. Journal of Affective Disorders, 286. pp. 275-281. ISSN 0165-0327

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Abstract

Background
Decreased cholinergic tone associated with increased proinflammatory cytokines has been observed in several human diseases associated with low-grade inflammation. We examined if this attenuated cholinergic anti-inflammatory pathway (CAP) mechanism contributed to increased neuroinflammation observed in depression.

Methods
We measured cerebrospinal fluid (CSF) cholinergic markers (AChE and BChE activities) in 28 individuals with longstanding late-life major depression (LLMD) and 19 controls and their relationship to central and peripheral levels of pro-inflammatory cytokines (IL-6 and IL-8). Additionally, we examined if these cholinergic indices were related to CSF markers of microglial activation and neuroinflammation (sTREM2 and complement C3).

Results
Compared with controls, LLMD patients had a significant reduction in CSF BChE levels. Lower CSF BChE and AChE activities were associated with lower CSF markers of microglial and neuroinflammation (sTREM2 and C3). In addition, in LLMD patients we found an inverse relationship between peripheral marker of inflammation (plasma IL-6) and CSF BChE and AChE levels.

Conclusions
Our results suggest an upregulation of the CAP mechanism in LLMD with an elevation in peripheral markers of inflammation and concomitant reduction in markers of glial activation associated with a higher cholinergic tone. Future studies should confirm these findings in a larger sample including individuals with acute and more severe depressive episodes and across all ages.

Item Type: Article
Uncontrolled Keywords: 11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RM Therapeutics. Pharmacology
Divisions: Psychology (new Sep 2019)
Publisher: Elsevier
Date Deposited: 04 Mar 2021 12:10
Last Modified: 07 Jan 2022 15:30
DOI or Identification number: 10.1016/j.jad.2021.03.012
URI: https://researchonline.ljmu.ac.uk/id/eprint/14548

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