Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Augmenting extinction learning with D-cycloserine reduces return of fear: a randomized, placebo-controlled fMRI study.
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Circuit-informed modulation of traumatic memory in PTSD: integrating extinction, suppression, and reconsolidation.Molecular psychiatry · 2026Review
- Enhancing the Efficacy of Exposure Therapy: Translation of Pharmacological Augmentation of Fear Extinction.Annual review of clinical psychology · 2026Review
- Sweetening fear exposure: study protocol for a multi-day, randomized controlled trial to study effects of glucose in exposure sessions of participants with public speaking anxiety.BMC psychology · 2026Article
- Approved and Pipeline Pharmacological Interventions for Eating Disorders (2010-2025): 15 Years of Progress (or Lack Thereof).CNS drugs · 2026Review
- A systematic review of spontaneous recovery in human fear conditioning.Frontiers in behavioral neuroscience · 2026Review
- Cortisol Imbalance and Fear Learning in PTSD: Therapeutic Approaches to Control Abnormal Fear Responses.Current neuropharmacology · 2025Review
- Memory persistence: from fundamental mechanisms to translational opportunities.Translational psychiatry · 2024Review
- Exercise and Fear and Safety Learning.Current topics in behavioral neurosciences · 2024Review
- Neuropharmacological Modulation of N-methyl-D-aspartate, Noradrenaline and Endocannabinoid Receptors in Fear Extinction Learning: Synaptic Transmission and Plasticity.International journal of molecular sciences · 2023Review
- Aerobic exercise in the treatment of PTSD: An examination of preclinical and clinical laboratory findings, potential mechanisms, clinical implications, and future directions.Journal of anxiety disorders · 2023Review
- Targeting NMDA Receptors in Emotional Disorders: Their Role in Neuroprotection.Brain sciences · 2022Review
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- Article
- D-Serine as the gatekeeper of NMDA receptor activity: implications for the pharmacologic management of anxiety disorders.Translational psychiatry · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.