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1.  Amphetamine induced dopamine release increases anxiety in individuals recovered from anorexia nervosa 
Genetic, pharmacologic, and physiological data suggest that individuals with anorexia nervosa (AN) have altered striatal dopamine (DA) function.
We used an amphetamine challenge and positron emission tomography [11C]raclopride paradigm to explore DA striatal transmission in 10 recovered (REC) AN compared to 9 control women (CW).
REC AN and CW were similar for baseline, post-amphetamine [11C]raclopride binding potential (BPND) and change (Δ) in BPND for all regions. In CW, ventral striatum Δ BPND was associated with euphoria (r = − .76; p = .03), which was not found for REC AN. Instead, REC AN showed a significant relationship between anxiety and Δ BPND in the pre-commissural dorsal caudate (r = −.62, p = .05).
REC AN have a positive association between endogenous DA release and anxiety in the dorsal caudate. This finding could explain why food-related DA release produces anxiety in AN, whereas feeding is pleasurable in healthy participants.
PMCID: PMC3151352  PMID: 21541980
anorexia nervosa; amphetamine; dopamine; anxiety; positron emission tomography
2.  Differential weight restoration on olanzapine versus fluoxetine in identical twins with anorexia nervosa 
No studies have compared the response to selective serotonin reuptake inhibitors and atypical antipsychotics in anorexia nervosa. This case study examines such a comparison.
This report describes a case of 12-year-old identical twins with anorexia nervosa, one of whom was treated with olanzapine and the other with fluoxetine, while undergoing family therapy.
Twin A treated with fluoxetine went from 75% to 84.4% ideal body weight, while Twin B treated with olanzapine went from 72% to 99.9% ideal body weight over the course of 9 months.
This case supports the need for adequately powered, controlled clinical trials to test the efficacy of olanzapine in adolescents presenting with anorexia nervosa.
PMCID: PMC3579522  PMID: 21344468
3.  Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs 
Neuropsychopharmacology  2011;36(11):2222-2232.
Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, ‘ill') or absence (n=115 no symptoms in the past year, ie, ‘recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10−6, false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10−6, FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (γ-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients.
PMCID: PMC3176559  PMID: 21750581
GABA; anorexia nervosa; recovery from eating disorders; genetic association; single nucleotide polymorphisms; eating/metabolic disorders; GABA; eating/metabolic disorders; neurogenetics; biological psychiatry; genetic association; anorexia nervosa; recovery from eating disorders; single-nucleotide polymorphisms; phenomic association
4.  5-HT1A receptor activation is necessary for 5-MeODMT-dependent potentiation of feeding inhibition 
We propose a translational approach to the study of anorexia nervosa (AN) based on our human subject studies where there are characteristic elevations in 5-HT1A receptor binding, associated harm avoidance behaviors, reduced impulsivity, and comorbid anxiety disorders. Towards this goal, the hyponeophagia assay was implemented whereby food-deprived mice show increased latency to begin feeding in a novel, anxiogenic environment. The non-selective serotonin agonist, 5-MeODMT, potentiates feeding inhibition compared to the inhibition generated by the anxiogenic environment in a drug-by-environment interaction. Thus, using hyponeophagia in mice, it was possible to study the following key components of AN: anxiety; feeding inhibition; and a modulatory role of the serotonergic system. A major prediction of the proposed AN model is that 5-HT1A receptor activation is necessary for feeding inhibition. In support of this model, the 5-HT1A receptor antagonist, WAY100635, reverses the 5-MeODMT-dependent potentiation of feeding inhibition. Our findings hint at a mechanistic role for increased 5-HT1A receptor activation in restricting-type AN. Further implications for the interplay between anxiety and feeding inhibition in AN are discussed.
PMCID: PMC2724836  PMID: 19490926
Serotonin; Anorexia; Feeding; Anxiety; Impulsivity; Novelty

Results 1-4 (4)