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  Ketamine influences the locus coeruleus norepinephrine network, with a dependency on norepinephrine transporter genotype: a placebo controlled fMRI study

Liebe, T., Li, M., Colic, L., Munk, M., Sweeney-Reed, C., Woelfer, M., et al. (2018). Ketamine influences the locus coeruleus norepinephrine network, with a dependency on norepinephrine transporter genotype: a placebo controlled fMRI study. NeuroImage: Clinical, 20, 715-723. doi:10.1016/j.nicl.2018.09.001.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-4425-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-4426-7
Genre: Journal Article

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 Creators:
Liebe, T, Author
Li, M, Author
Colic, L, Author
Munk, M, Author              
Sweeney-Reed , CM, Author
Woelfer, M, Author
Kretzschmar, MA, Author
Steiner, J, Author
von Düring, F, Author
Behnisch, G, Author
Schott, BH, Author
Walter, M1, 2, Author              
Affiliations:
1Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497796              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: Background Ketamine is receiving increasing attention as a rapid-onset antidepressant in patients suffering from major depressive disorder (MDD) with treatment resistance or severe suicidal ideation. Ketamine modulates several neurotransmitter systems, including norepinephrine via the norepinephrine transporter (NET), both peripherally and centrally. The locus coeruleus (LC), which has high NET concentration, has been attributed to brain networks involved in depression. Thus we investigated the effects of single-dose of racemic ketamine on the LC using resting state functional MRI. Methods Fifty-nine healthy participants (mean age 25.57 ± 4.72) were examined in a double-blind, randomized, placebo-controlled study with 7 Tesla MRI. We investigated the resting state functional connectivity (rs-fc) of the LC before and one hour after subanesthetic ketamine injection (0.5 mg/kg), as well as associations between its rs-fc and a common polymorphism in the NET gene (rs28386840). Results A significant interaction of drug and time was revealed, and post hoc testing showed decreased rs-fc between LC and the thalamus after ketamine administration compared with baseline levels, including the mediodorsal, ventral anterior, ventral lateral, ventral posterolateral and centromedian nuclei. The rs-fc reduction was more pronounced in NET rs28386840 [AA] homozygous subjects than in [T] carriers. Conclusions We demonstrated acute rs-fc changes after ketamine administration in the central node of the norepinephrine pathway. These findings may contribute to understanding the antidepressant effect of ketamine at the system level, supporting modes of action on networks subserving aberrant arousal regulation in depression.

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 Dates: 2018-09
 Publication Status: Published in print
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 Identifiers: DOI: 10.1016/j.nicl.2018.09.001
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Title: NeuroImage: Clinical
Source Genre: Journal
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Publ. Info: Elsevier
Pages: - Volume / Issue: 20 Sequence Number: - Start / End Page: 715 - 723 Identifier: ISSN: 2213-1582
CoNE: https://pure.mpg.de/cone/journals/resource/2213-1582