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Updated: Jul 24, 2025

Simultaneous Application of Transcranial Direct Current Stimulation during Virtual Reality Exposure
Published on: January 18, 2021
Using pre-treatment de novo threat conditioning outcomes to predict treatment response to DCS augmentation of
Rebecca E Lubin1, Hayley E Fitzgerald1, David Rosenfield2
1Department of Psychological and Brain Sciences, Boston University, 900 Commonwealth Ave, 2nd Fl, Boston, MA, 02215, USA.
Background:
Over a decade and a half of research has resulted in inconsistent evidence for the efficacy of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, for augmenting exposure-based cognitive behavioral therapy (CBT) for anxiety- and fear-based disorders. These variable findings have motivated the search for moderators of DCS augmentation efficacy.
Methods:
In this secondary analysis of a previous randomized clinical trial, we evaluated the value of de novo threat conditioning outcomes-degree of threat acquisition, extinction, and extinction retention-for predicting treatment response to exposure-based CBT for social anxiety disorder, applied with and without DCS augmentation in a sample of 59 outpatients.
Results:
We found that average differential skin conductance response (SCR) during extinction and extinction retention significantly moderated the prediction of clinical response to DCS: participants with poorer extinction and extinction retention showed relatively improved treatment response with DCS. No such effects were found for expectancy ratings, consistent with accounts of DCS selectively aiding lower-order but not higher-order extinction learning.
Conclusions:
These findings provide support for extinction and extinction retention outcomes from threat conditioning as potential pre-treatment biomarkers for DCS augmentation benefits. Independent of DCS augmentation, the current study did not support threat conditioning outcomes as useful for predicting response to exposure-based CBT.
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