An fMRI study examining effects of acute D-cycloserine during symptom provocation in spider phobia.
BACKGROUND
Exposure-based therapy for anxiety disorders is believed to operate on the basis of fear extinction. Studies have shown acute administration of D-cycloserine (DCS) enhances fear extinction in animals and facilitates exposure therapy in humans, but the neural mechanisms are not completely understood. To date, no study has examined neural effects of acute DCS in anxiety-disordered populations.


METHODS
Two hours prior to functional magnetic resonance imaging scanning, 23 spider-phobic and 23 non-phobic participants were randomized to receive DCS 100 mg or placebo. During scanning, participants viewed spider, butterfly, and Gaussian-blurred baseline images in a block-design paradigm. Diagnostic and treatment groups were compared regarding differential activations to spider versus butterfly stimuli.


RESULTS
In the phobic group, DCS enhanced prefrontal (PFC), dorsal anterior cingulate (ACC), and insula activations. For controls, DCS enhanced ventral ACC and caudate activations. There was a positive correlation between lateral PFC and amygdala activation for the placebo-phobic group. Reported distress during symptom provocation was correlated with amygdala activation in the placebo-phobic group and orbitofrontal cortex activation in the DCS-phobic group.


CONCLUSIONS
Results suggest that during initial phobic symptom provocation DCS enhances activation in regions involved in cognitive control and interoceptive integration, including the PFC, ACC, and insular cortices for phobic participants.
Aupperle
Robin L
RL
Department of Psychiatry, University of California, San Diego, USA.
Hale
Lisa R
LR
Chambers
Rebecca J
RJ
Cain
Sharon E
SE
Barth
Frank X
FX
Sharp
Susan C
SC
Denney
Douglas R
DR
Savage
Cary R
CR
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D001931:Brain Mapping; D003523:Cycloserine / Q000627:therapeutic use*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010100:Oxygen / Q000097:blood; D010698:Phobic Disorders / Q000175:diagnosis* / Q000188:drug therapy*; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D013112:Spiders; D011795:Surveys and Questionnaires; D055815:Young Adult
D000904:Antibiotics, Antitubercular; D003523:Cycloserine; D010100:Oxygen