Dataset Information

Bipolar disorder with binge eating behavior: a genome-wide association study implicates PRR5-ARHGAP8.

ABSTRACT: Bipolar disorder (BD) is associated with binge eating behavior (BE), and both conditions are heritable. Previously, using data from the Genetic Association Information Network (GAIN) study of BD, we performed genome-wide association (GWA) analyses of BD with BE comorbidity. Here, utilizing data from the Mayo Clinic BD Biobank (969 BD cases, 777 controls), we performed a GWA analysis of a BD subtype defined by BE, and case-only analysis comparing BD subjects with and without BE. We then performed a meta-analysis of the Mayo and GAIN results. The meta-analysis provided genome-wide significant evidence of association between single nucleotide polymorphisms (SNPs) in PRR5-ARHGAP8 and BE in BD cases (rs726170 OR?=?1.91, P?=?3.05E-08). In the meta-analysis comparing cases with BD with comorbid BE vs. non-BD controls, a genome-wide significant association was observed at SNP rs111940429 in an intergenic region near PPP1R2P5 (p?=?1.21E-08). PRR5-ARHGAP8 is a read-through transcript resulting in a fusion protein of PRR5 and ARHGAP8. PRR5 encodes a subunit of mTORC2, a serine/threonine kinase that participates in food intake regulation, while ARHGAP8 encodes a member of the RhoGAP family of proteins that mediate cross-talk between Rho GTPases and other signaling pathways. Without BE information in controls, it is not possible to determine whether the observed association reflects a risk factor for BE in general, risk for BE in individuals with BD, or risk of a subtype of BD with BE. The effect of PRR5-ARHGAP8 on BE risk thus warrants further investigation.

SUBMITTER: McElroy SL

PROVIDER: S-EPMC5804024 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Bipolar disorder with binge eating behavior: a genome-wide association study implicates PRR5-ARHGAP8.

McElroy Susan L SL Winham Stacey J SJ Cuellar-Barboza Alfredo B AB Colby Colin L CL Ho Ada Man-Choi AM Sicotte Hugues H Larrabee Beth R BR Crow Scott S Frye Mark A MA Biernacka Joanna M JM

Translational psychiatry 20180202 1

Bipolar disorder (BD) is associated with binge eating behavior (BE), and both conditions are heritable. Previously, using data from the Genetic Association Information Network (GAIN) study of BD, we performed genome-wide association (GWA) analyses of BD with BE comorbidity. Here, utilizing data from the Mayo Clinic BD Biobank (969 BD cases, 777 controls), we performed a GWA analysis of a BD subtype defined by BE, and case-only analysis comparing BD subjects with and without BE. We then performed ...[more]

PMID: 29391396

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Project description:BackgroundCurrent guidelines recommend cognitive behavior therapy (CBT) as the treatment of choice for binge eating disorder (BED). Although CBT is quite effective, a substantial number of patients do not reach abstinence from binge eating. To tackle this problem, various theoretical conceptualizations and treatment models have been proposed. Dialectical behavior therapy (DBT), focusing on emotion regulation, is one such model. Preliminary evidence comparing DBT adapted for BED (DBT-BED) to CBT is promising but the available data do not favor one treatment over the other. The aim of this study is to evaluate outcome of DBT-BED, compared to a more intensive eating disorders-focused form of cognitive behavior therapy (CBT+), in individuals with BED who are overweight and engage in emotional eating.MethodsSeventy-four obese patients with BED who reported above average levels of emotional eating were quasi-randomly allocated to one of two manualized 20-session group treatments: DBT-BED (n = 41) or CBT+ (n = 33). Intention-to-treat outcome was examined at post-treatment and at 6-month follow-up using general or generalized linear models with multiple imputation.ResultsOverall, greater improvements were observed in CBT+. Differences in number of objective binge eating episodes at end of treatment, and eating disorder psychopathology (EDE-Q Global score) and self-esteem (EDI-3 Low Self-Esteem) at follow-up reached statistical significance with medium effect sizes (Cohen's d between .46 and .59). Of the patients in the DBT group, 69.9% reached clinically significant change at end of the treatment vs 65.0% at follow-up. Although higher, this was not significantly different from the patients in the CBT+ group (52.9% vs 45.8%).ConclusionsThe results of this study show that CBT+ produces better outcomes than the less intensive DBT-BED on several measures. Yet, regardless of the dose-difference, the data suggest that DBT-BED and CBT+ lead to comparable levels of clinically meaningful change in global eating disorder psychopathology. Future recommendations include the need for dose-matched comparisons in a sufficiently powered randomized controlled trial, and the need to determine mediators and moderators of treatment outcome.Trial registrationNederlands Trial Register: NL3982 (NTR4154). Date of registration: 2013 August 28, retrospectively registered.

Dataset Information

Bipolar disorder with binge eating behavior: a genome-wide association study implicates PRR5-ARHGAP8.

Publications

Bipolar disorder with binge eating behavior: a genome-wide association study implicates PRR5-ARHGAP8.

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