Abstract
Preclinical and clinical data have shown that D-cycloserine (DCS), a partial agonist at the N-methyl-d-aspartate receptor complex, augments the retention of fear extinction in animals and the therapeutic learning from exposure therapy in humans. However, studies with non-clinical human samples in de novo fear conditioning paradigms have demonstrated minimal to no benefit of DCS. The aim of this study was to evaluate the effects of DCS on the retention of extinction learning following de novo fear conditioning in a clinical sample. Eighty-one patients with social anxiety disorder were recruited and underwent a previously validated de novo fear conditioning and extinction paradigm over the course of three days. Of those, only 43 (53%) provided analyzable data. During conditioning on Day 1, participants viewed images of differently colored lamps, two of which were followed by with electric shock (CS+) and a third which was not (CS-). On Day 2, participants were randomly assigned to receive either 50 mg DCS or placebo, administered in a double-blind manner 1 hour prior to extinction training with a single CS+ in a distinct context. Day 3 consisted of tests of extinction recall and renewal. The primary outcome was skin conductance response to conditioned stimuli, and shock expectancy ratings were examined as a secondary outcome. Results showed greater skin conductance and expectancy ratings in response to the CS+ compared to CS- at the end of conditioning. As expected, this difference was no longer present at the end of extinction training, but returned at early recall and renewal phases on Day 3, showing evidence of return of fear. In contrast to hypotheses, DCS had no moderating influence on skin conductance response or expectancy of shock during recall or renewal phases. We did not find evidence of an effect of DCS on the retention of extinction learning in humans in this fear conditioning and extinction paradigm.
Highlights
Exposure-based treatment for the anxiety-related disorders offers some of the strongest treatment outcomes in the literature [1,2]
Of the 81 participants who participated in the fear conditioning paradigm, 12 had unusable skin conductance response (SCR) data due to equipment malfunctioning
No differential effects were obtained relative to those reported below, and we report these results as supplementary material
Summary
Exposure-based treatment for the anxiety-related disorders offers some of the strongest treatment outcomes in the literature [1,2]. A number of efforts are underway to strengthen the efficacy and durability of extinction learning from exposure therapy [5]. In addition to diagnostic variability, DCS augmentation studies differ in the amount of exposure therapy offered, the elements of treatment in addition to exposure, and the amount and timing of DCS administrations relative to the start of exposure treatment [6]. Any of these factors could introduce variability into estimates of the efficacy of DCS augmentation
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