PT  - JOURNAL ARTICLE
AU  - Andrea Reinecke
AU  - Alecia Nickless
AU  - Michael Browning
AU  - Catherine J. Harmer
TI  - Neurocognitive mechanisms of d-cycloserine augmented single-session exposure therapy for anxiety
AID  - 10.1101/615757
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 615757
4099  - http://biorxiv.org/content/early/2019/04/26/615757.short
4100  - http://biorxiv.org/content/early/2019/04/26/615757.full
AB  - Drugs targeting the N-Methyl-D-aspartic acid (NMDA) system and learning rates have been proposed as potential adjunct treatments to boost the success of exposure therapy for anxiety disorders. However, the effects of the NMDA partial agonist d-cycloserine on psychological treatment have been mixed. We investigated potential neurocognitive mechanisms underlying the clinical effects of d-cycloserine-augmented exposure, to inform the optimal combination of this and similar agents with psychological treatment. Unmedicated patients with panic disorder were randomised to single-dose d-cycloserine (250mg; N=17) or matching placebo (N=16) 2hrs before one session of exposure therapy. Neurocognitive markers were assessed one day after treatment, including reaction-time based threat bias for fearful faces and amygdala response to threat. Clinical symptom severity was measured using self-report and clinician-rated scales the day before and after treatment, and at 1- and 6-months follow-up. Analysis was by intention-to-treat. One day after treatment, threat bias for fearful faces and amygdala threat response were attenuated in the drug compared to the placebo group. Lower amygdala magnitude predicted greater clinical improvement during follow-up across groups. D-cycloserine led to greater clinical recovery at 1-month follow-up (d-cycloserine 71% versus placebo 25%). D-cycloserine-augmented single-session exposure therapy reduces amygdala threat response, and this effect predicts later clinical response. These findings highlight a neurocognitive mechanism by which d-cycloserine may exert its augmentative effects on psychological treatment and bring forward a marker that may help understand and facilitate future development of adjunct treatments with CBT for anxiety disorders. (D-cycloserine Augmented CBT for Panic Disorder; clinicaltrials.gov; NCT01680107)