title: Extinction learning as a moderator of d-cycloserine efficacy for enhancing exposure therapy in posttraumatic stress disorder.
abstract: Augmentation of exposure therapy with d-cycloserine (DCS) has proven efficacious across anxiety disorders, although results in PTSD have been mixed. Work in animals and anxiety-disordered patients suggest that the potentiating effects of DCS are dependent on the level of extinction learning during extinction training and exposure treatment, respectively. The aim of the current study was to replicate and extend previous work by examining the association between the degree of extinction learning and DCS efficacy in our randomized clinical trial on DCS (50 mg) versus placebo enhancement of exposure therapy in a chronic mixed-trauma PTSD sample (N=67; de Kleine, Hendriks, Kusters, Broekman, & van Minnen, 2012). The decline in subjective units of distress ratings collected during and across the exposure sessions were evaluated as indices of extinction learning. First, we examined whether extinction learning during an exposure session moderated DCS effects on self-reported PTSD symptoms at the next session. Second, we examined whether averaged extinction learning over the course of treatment interacted with group assignment to predict change over time and post treatment outcome. We did not find evidence that DCS effects were moderated by the degree of extinction learning, although, extinction learning was related to outcome regardless of group assignment. In PTSD, not one extinction-learning index has been consistently linked to DCS enhanced exposure treatment outcome. More (experimental) work needs to been done to unravel the complex interplay between extinction learning and DCS enhancement, especially in PTSD patients.
authors.affiliation: Center for Anxiety Disorders Overwaal, Institution for Integrated Mental Health Care Pro Persona, Nijmegen, The Netherlands; Radboud University, Behavioural Science Institute, NijCare, Nijmegen, the Netherlands. Electronic address: r.de.kleine@propersona.nl.
authors.forename: Rianne A
authors.initials: RA
authors.lastname: de Kleine
authors.affiliation: The University of Texas at Austin, Department of Psychology and Institute for Mental Health Research, Austin, TX, United States.
authors.forename: Jasper A J
authors.initials: JA
authors.lastname: Smits
authors.affiliation: Center for Anxiety Disorders Overwaal, Institution for Integrated Mental Health Care Pro Persona, Nijmegen, The Netherlands; Radboud University, Behavioural Science Institute, NijCare, Nijmegen, the Netherlands; Radboud University Medical Centre, Department of Psychiatry, Nijmegen, The Netherlands.
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Hendriks
authors.affiliation: Radboud University, Behavioural Science Institute, NijCare, Nijmegen, the Netherlands.
authors.forename: Eni S
authors.initials: ES
authors.lastname: Becker
authors.affiliation: Center for Anxiety Disorders Overwaal, Institution for Integrated Mental Health Care Pro Persona, Nijmegen, The Netherlands; Radboud University, Behavioural Science Institute, NijCare, Nijmegen, the Netherlands.
authors.forename: Agnes
authors.initials: A
authors.lastname: van Minnen
mesh_terms: D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy; D003131:Combined Modality Therapy; D003523:Cycloserine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005108:Extinction, Psychological; D005239:Fear / Q000523:psychology; D005260:Female; D006801:Humans; D007171:Implosive Therapy / Q000379:methods*; D007858:Learning; D008297:Male; D057566:Self Report; D013313:Stress Disorders, Post-Traumatic / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D014151:Anti-Anxiety Agents; D003523:Cycloserine
keywords: Extinction learning; Moderation; Posttraumatic stress disorder; d-cycloserine