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Association of CSF sTREM2, a marker of microglia activation, with cholinergic basal forebrain volume in major depressive disorder

Teipel, S; Bruno, D; Plaska, CR; Heslegrave, A; Ramos-Cejudo, J; Osorio, RS; Zetterberg, H; ... Pomara, N; + view all (2021) Association of CSF sTREM2, a marker of microglia activation, with cholinergic basal forebrain volume in major depressive disorder. Journal of Affective Disorders , 293 pp. 429-434. 10.1016/j.jad.2021.06.030. Green open access

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Abstract

BACKGROUND: Inflammatory mechanisms are believed to contribute to the manifestation of major depressive disorder (MDD). Central cholinergic activity may moderate this effect. Here, we tested if volume of the cholinergic basal forebrain is associated with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglial activation in people with late life MDD. METHODS: Basal forebrain volume was determined from structural MRI scans and levels of CSF sTREM2 with immunoassay in 29 people with late-life MDD and 20 healthy older controls at baseline and 3 years follow-up. Associations were determined using Bayesian analysis of covariance. RESULTS: We found moderate level of evidence for an association of lower CSF levels of sTREM2 at 3 years follow up with MDD (Bayes factor in favor of an effect = 7.9). This level of evidence prevailed when controlling for overall antidepressant treatment and CSF levels of markers of AD pathology, i.e., Aβ42/Aβ40, ptau181 and total tau. Evidence was in favor of absence of an effect for baseline levels of CSF sTREM2 in MDD cases and for baseline and follow up data in controls. LIMITATIONS: The sample size of repeated CSF examinations was relatively small. Therefore, we used Bayesian sequential analysis to assess if effects were affected by sample size. Still, the number of cases was too small to stratify effects for different antidepressive treatments. CONCLUSIONS: Our data agree with the assumption that central cholinergic system integrity may contribute to regulation of microglia activity in late-life MDD.

Type: Article
Title: Association of CSF sTREM2, a marker of microglia activation, with cholinergic basal forebrain volume in major depressive disorder
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jad.2021.06.030
Publisher version: http://dx.doi.org/10.1016/j.jad.2021.06.030
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Basal forebrain, Cerebrospinal fluid, Late life major depressive disorder, MRI, Microglia activation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10131991
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