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D-Cycloserine facilitation of exposure therapy improves weight regain in patients with anorexia nervosa: a pilot randomized controlled trial.

ABSTRACT: Exposure therapy in anorexia nervosa has preliminarily been shown to be effective for increasing food intake. D-Cycloserine is a glutamatergic N-methyl-d-aspartate receptor agonist that has been shown to facilitate the benefits of exposure therapy for anxiety disorders by enhancing the emotional learning in the exposures; therefore, we examined D-cycloserine-facilitation of exposure therapy to increase body mass index (BMI) in patients with anorexia nervosa.Participants (N = 36) with anorexia nervosa (diagnosed via DSM-IV) were recruited from a partial hospitalization eating disorder clinic between February 2013 and November 2013. Participants were randomly assigned to receive exposure therapy plus D-cycloserine (n = 20) or placebo (n = 16). Participants completed psychoeducation and 4 sessions of exposure therapy, with medication (D-cycloserine vs placebo) given prior to the first 3 exposure sessions. They also completed a 1-month follow-up.As hypothesized, participants in the D-cycloserine group showed a significantly greater increase in BMI than those in the placebo group (Wilk ? = 0.86, F3,32 = 2.20, P = .043, ?p(2) = 0.12). D-Cycloserine participants gained 3 pounds relative to 0.5 pounds in the placebo group. Both groups experienced significantly decreased anxiety over the course of therapy (Wilk ? = 0.80, F3,32 = 3.32, P = .023, ?p(2) = 0.20).This study preliminarily demonstrates that D-cycloserine facilitates exposure therapy for anorexia nervosa, leading to increased weight gain. A potential mechanism is that participants who receive D-cycloserine may generalize learning from within-session exposures to food intake during other similar meals, resulting in sustained increases in BMI. Further research is needed to confirm these findings and test the putative mechanism that generalized learning from exposure therapy can increase BMI and stabilize a healthy weight.ClinicalTrials.gov identifier: NCT01996644.

SUBMITTER: Levinson CA

PROVIDER: S-EPMC4801774 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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D-Cycloserine facilitation of exposure therapy improves weight regain in patients with anorexia nervosa: a pilot randomized controlled trial.

Levinson Cheri A CA Rodebaugh Thomas L TL Fewell Laura L Kass Andrea E AE Riley Elizabeth N EN Stark Lynn L McCallum Kimberly K Lenze Eric J EJ

The Journal of clinical psychiatry 20150601 6

<h4>Objective</h4>Exposure therapy in anorexia nervosa has preliminarily been shown to be effective for increasing food intake. D-Cycloserine is a glutamatergic N-methyl-d-aspartate receptor agonist that has been shown to facilitate the benefits of exposure therapy for anxiety disorders by enhancing the emotional learning in the exposures; therefore, we examined D-cycloserine-facilitation of exposure therapy to increase body mass index (BMI) in patients with anorexia nervosa.<h4>Method</h4>Parti ...[more]

PMID: 26132687

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Project description:IntroductionDisruptions in homeostatic and hedonic food motivation are proposed to underlie anorexia nervosa (AN) and atypical AN, restrictive eating disorders which commonly onset in puberty. Ghrelin, a neuroprotective hormone that drives hedonic eating is increased in AN and is expressed in the hippocampus. White matter (WM) undergoes significant change during puberty in regions involved in food motivation, particularly WM tracts connected with the hippocampus. The association between ghrelin and WM region of interest (ROI) with hippocampal connections in restrictive eating disorders, particularly in adolescence during key neurodevelopmental growth, is unknown.MethodsWe evaluated fasting plasma ghrelin and WM microstructure (measured by free-water corrected fractional anisotropy (FA-t)) in WM ROIs with hippocampal connections - the fornix and the hippocampal portion of the cingulum - in 56 adolescent females (age range: 11.9 - 22.1 y; mean: 19.0 y) with low-weight eating disorders including AN and atypical AN (N = 36) and healthy controls (N = 20).ResultsFA-t in the fornix or hippocampal portion of the fornix did not differ between groups. Ghrelin was higher in AN/atypical AN vs. HC and was positively correlated with puberty stage in the AN/atypical AN group, but not the HC group. The correlation between ghrelin and FA-t in the fornix was significantly different in females with AN/atypical AN compared to controls. In AN/atypical AN, pubertal stage moderated the relation between fasting plasma ghrelin and FA-t in the fornix: higher fasting ghrelin was associated with lower FA-t in the fornix in late-post-puberty, but was not associated with FA-t in the early to mid stages of puberty.ConclusionsIn post-pubertal females with low-weight AN/atypical AN, higher levels of ghrelin are associated with lower FA-t in the fornix. This relationship is not evident in the early to mid stages of puberty in AN/atypical AN or in HC, and may reflect a lack of possible neuroprotective effects of ghrelin in late-post puberty only. Understanding the effects of ghrelin on WM microstructure longitudinally and following recovery from AN/Atypical AN and how this differs across pubertal stages will be an important next step. These findings could ultimately inform treatment staging and aid in diagnosis and detection of AN/atypical AN.

Dataset Information

D-Cycloserine facilitation of exposure therapy improves weight regain in patients with anorexia nervosa: a pilot randomized controlled trial.

Publications

D-Cycloserine facilitation of exposure therapy improves weight regain in patients with anorexia nervosa: a pilot randomized controlled trial.

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