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Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS).

Publication ,  Journal Article
Pizzagalli, DA; Smoski, M; Ang, Y-S; Whitton, AE; Sanacora, G; Mathew, SJ; Nurnberger, J; Lisanby, SH; Iosifescu, DV; Murrough, JW; Yang, H ...
Published in: Neuropsychopharmacology
September 2020

Anhedonia remains a major clinical issue for which there is few effective interventions. Untreated or poorly controlled anhedonia has been linked to worse disease course and increased suicidal behavior across disorders. Taking a proof-of-mechanism approach under the auspices of the National Institute of Mental Health FAST-FAIL initiative, we were the first to show that, in a transdiagnostic sample screened for elevated self-reported anhedonia, 8 weeks of treatment with a kappa-opioid receptor (KOR) antagonist resulted in significantly higher reward-related activation in one of the core hubs of the brain reward system (the ventral striatum), better reward learning in the Probabilistic Reward Task (PRT), and lower anhedonic symptoms, relative to 8 weeks of placebo. Here, we performed secondary analyses of the PRT data to investigate the putative effects of KOR antagonism on anhedonic behavior with more precision by using trial-level model-based Bayesian computational modeling and probability analyses. We found that, relative to placebo, KOR antagonism resulted in significantly higher learning rate (i.e., ability to learn from reward feedback) and a more sustained preference toward the more frequently rewarded stimulus, but unaltered reward sensitivity (i.e., the hedonic response to reward feedback). Collectively, these findings provide novel evidence that in a transdiagnostic sample characterized by elevated anhedonia, KOR antagonism improved the ability to modulate behavior as a function of prior rewards. Together with confirmation of target engagement in the primary report (Krystal et al., Nat Med, 2020), the current findings suggest that further transdiagnostic investigation of KOR antagonism for anhedonia is warranted.

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Published In

Neuropsychopharmacology

DOI

EISSN

1740-634X

Publication Date

September 2020

Volume

45

Issue

10

Start / End Page

1656 / 1663

Location

England

Related Subject Headings

  • United States
  • Psychiatry
  • Narcotic Antagonists
  • Humans
  • Bayes Theorem
  • Anxiety Disorders
  • Anxiety
  • Analgesics, Opioid
  • 5202 Biological psychology
  • 3209 Neurosciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pizzagalli, D. A., Smoski, M., Ang, Y.-S., Whitton, A. E., Sanacora, G., Mathew, S. J., … Krystal, A. D. (2020). Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS). Neuropsychopharmacology, 45(10), 1656–1663. https://doi.org/10.1038/s41386-020-0738-4
Pizzagalli, Diego A., Moria Smoski, Yuen-Siang Ang, Alexis E. Whitton, Gerard Sanacora, Sanjay J. Mathew, John Nurnberger, et al. “Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS).Neuropsychopharmacology 45, no. 10 (September 2020): 1656–63. https://doi.org/10.1038/s41386-020-0738-4.
Pizzagalli DA, Smoski M, Ang Y-S, Whitton AE, Sanacora G, Mathew SJ, et al. Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS). Neuropsychopharmacology. 2020 Sep;45(10):1656–63.
Pizzagalli, Diego A., et al. “Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS).Neuropsychopharmacology, vol. 45, no. 10, Sept. 2020, pp. 1656–63. Pubmed, doi:10.1038/s41386-020-0738-4.
Pizzagalli DA, Smoski M, Ang Y-S, Whitton AE, Sanacora G, Mathew SJ, Nurnberger J, Lisanby SH, Iosifescu DV, Murrough JW, Yang H, Weiner RD, Calabrese JR, Goodman W, Potter WZ, Krystal AD. Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS). Neuropsychopharmacology. 2020 Sep;45(10):1656–1663.

Published In

Neuropsychopharmacology

DOI

EISSN

1740-634X

Publication Date

September 2020

Volume

45

Issue

10

Start / End Page

1656 / 1663

Location

England

Related Subject Headings

  • United States
  • Psychiatry
  • Narcotic Antagonists
  • Humans
  • Bayes Theorem
  • Anxiety Disorders
  • Anxiety
  • Analgesics, Opioid
  • 5202 Biological psychology
  • 3209 Neurosciences