Molecular neuroanatomy of anorexia nervosa.

Anorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using genome-wide methods, recent studies have associated many genes with the disorder. We characterized these genes by projecting them into reference transcriptomic atlases of the prenatal and adult human brain to determine where these genes are expressed in fine detail. We found that genes from an induced stem cell study of anorexia nervosa cases are expressed at higher levels in the lateral parabrachial nucleus. Although weaker, expression enrichment of the adult lateral parabrachial is also found with genes from independent genetic studies. Candidate causal genes from the largest genetic study of anorexia nervosa to date were enriched for expression in the arcuate nucleus of the hypothalamus. We also found an enrichment of anorexia nervosa associated genes in the adult and fetal raphe and ventral tegmental areas. Motivated by enrichment of these feeding circuits, we tested if these genes respond to fasting in mice hypothalami, which highlighted the differential expression of Rps26 and Dalrd3. This work improves our understanding of the neurobiology of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.

A randomized comparison of long acting methylphenidate and cognitive behavioral therapy in the treatment of binge eating disorder.

Cognitive behavioral therapy (CBT) is a well-established treatment for binge eating disorder (BED); however, this treatment is underutilized, highlighting the need for additional treatment alternatives. Dopamine neurotransmission has been associated with dysregulated eating, and pharmaceutical agents targeting the dopamine system are associated with decreased binge eating and weight. The primary objective of the current investigation was to evaluate the efficacy of psychostimulant medication versus current best practices in the treatment of BED symptoms, in a randomized trial of methylphenidate versus CBT for BED. The secondary objective was to evaluate the ability of impulsivity to predict treatment outcomes. Female outpatients with BED were randomized to receive methylphenidate (n = 22) or CBT (n = 27) for 12 weeks. The primary outcome was objective binge episode frequency; secondary outcomes included subjective binge episode frequency, body mass index (BMI), BED symptoms, and quality of life. Results showed that both treatments had a significant impact on primary and secondary outcomes. Methylphenidate and CBT were associated with decreases in subjective and objective binge episodes; methylphenidate was associated with greater decreases in BMI. Two impulsivity traits predicted clinical outcomes. Results provide preliminary support for the therapeutic benefit of methylphenidate in BED treatment, and prognostic utility of impulsivity in this context.