Using pre-treatment de novo threat conditioning outcomes to predict treatment response to DCS augmentation of exposure-based CBT.

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.
Competing Interests: Declaration of competing interest The authors would like to acknowledge the following relationships: Dr. Otto receives compensation as a consultant for Big Health. Dr. Smits reports personal fees from Big Health, Ltd., Elsevier, the American Psychological Association, and Oxford University Press, and serves as advisor for Earkick. Dr. Pollack is currently an employee of Sage Therapeutics and a co-founder of Argus Cognitive. Dr. Hofmann receives financial support by the Alexander von Humboldt Foundation (as part of the Alexander von Humboldt Professur), the Hessische Ministerium für Wissenschaft und Kunst (as part of the LOEWE Spitzenprofessur), NIH/NIMH R01MH128377, NIH/NIMHU01MH108168, Broderick Foundation/MIT, and the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition – Special Initiative. He receives compensation for his work as editor from SpringerNature. He also receives royalties and payments for his work from various publishers. Dr. Dowd is a consultant for the Wellness Network. No other authors have relevant financial or non-financial interests to report.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)