Augmenting extinction learning with D-cycloserine reduces return of fear: A 
randomized, placebo-controlled fMRI study

Ebrahimi, Claudia; Gechter, Johanna; Lueken, Ulrike; Schlagenhauf, Florian; Wittchen, Hans-Ulrich; Hamm, Alfons O.; Ströhle, Andreas

doi:10.1038/s41386-019-0552-z

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Augmenting extinction learning with D-cycloserine reduces return of fear: A randomized, placebo-controlled fMRI study

Ebrahimi, C., Gechter, J., Lueken, U., Schlagenhauf, F., Wittchen, H.-U., Hamm, A. O., et al. (2020). Augmenting extinction learning with D-cycloserine reduces return of fear: A randomized, placebo-controlled fMRI study. Neuropsychopharmacology, 45(3), 499-506. doi:10.1038/s41386-019-0552-z.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0005-BEFE-8 Version Permalink: https://hdl.handle.net/21.11116/0000-000C-DD96-2

Genre: Journal Article

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https://www.nature.com/articles/s41386-019-0552-z (Publisher version) Open Access Green

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Creators:
Ebrahimi, Claudia¹, Author
Gechter, Johanna¹, Author
Lueken, Ulrike², Author
Schlagenhauf, Florian^{1, 3}, Author
Wittchen, Hans-Ulrich^{4, 5}, Author
Hamm, Alfons O.⁶, Author
Ströhle, Andreas¹, Author

Affiliations:
1Charité University Medicine Berlin, Germany, ou_persistent22
2Department of Psychology, Humboldt University Berlin, Germany, ou_persistent22
3Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549
4Department of Psychiatry and Psychotherapy, TU Dresden, Germany, ou_persistent22
5Department of Psychiatry and Psychotherapy, Ludwig Maximilians University Munich, Germany, ou_persistent22
6Institute of Physiological and Clinical Psychology, Ernst Moritz Arndt University of Greifswald, Germany, ou_persistent22

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Free keywords: Consolidation; Extinction; Fear conditioning

Abstract: d-cycloserine (DCS), a partial NMDA-receptor agonist, seems to be a promising enhancer for exposure therapy in anxiety disorders. It has been tested successfully in animal models of fear extinction, where DCS enhanced extinction learning. Applied in clinical studies, results of DCS-augmented exposure therapy remain ambiguous, calling for a deeper understanding of the underlying mechanisms of DCS and its exact effect on extinction learning and return of fear (ROF) in humans. In the present study, we investigated the effect of DCS-augmented extinction learning on behavioral, psychophysiological, and neural indices of ROF during a 24-h delayed recall test. Thirty-seven participants entered a randomized, placebo-controlled, double-blind, 3-day fear conditioning and delayed extinction fMRI design. One hour before extinction training, participants received an oral dose of 50 mg of DCS or a placebo. Behavioral arousal ratings revealed a generalized ROF during extinction recall in the placebo but not DCS group. Furthermore, participants receiving DCS compared to placebo showed attenuated differential BOLD responses in left posterior hippocampus and amygdala from extinction learning to extinction recall, due to increased hippocampal recruitment in placebo and trendwise decreased amygdala responding in DCS subjects. Our finding that DCS reduces ROF in arousal ratings and neural structures subserving defensive reactions support a role for NMDA receptors in extinction memory consolidation and encourage further translational research.

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Language(s): eng - English

Dates: Modified: 2019-09-22Submitted: 2019-05-25Accepted: 2019-10-14Published Online: 2019-10-21Date issued: 2020-02

Publication Status: Issued

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Identifiers: DOI: 10.1038/s41386-019-0552-z
Other: Epub 2019
PMID: 31634897
PMC: PMC6969173

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Grant ID : SCHL1969/4-1

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Funding organization : Deutsche Forschungsgemeinschaft (DFG)

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Grant ID : 01GV0612

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Funding organization : Bundesministerium für Bildung und Forschung (BMBF)

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Funding organization : Berlin Brandenburgische Akademie der Wissenschaften (BBAW)

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Funding organization : Eli Lilly International Foundation

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Funding organization : Robert-Enke-Stiftung and Lundbeck

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Funding organization : Stifterverband für die Deutsche Wissenschaft

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Funding organization : Eli Lilly and Company

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Funding organization : Pfizer

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Funding organization : UCB

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Funding organization : Cilag

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Funding program : Sixth Framework Programme

Funding organization : European Commission (EC)

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Funding organization : Boehringer Ingelheim Fonds

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Title: Neuropsychopharmacology

Source Genre: Journal

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Publ. Info: New York, NY

Pages: - Volume / Issue: 45 (3) Sequence Number: - Start / End Page: 499 - 506 Identifier: ISSN: 0893-133X
CoNE: https://pure.mpg.de/cone/journals/resource/954925558485