Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs

Bloss, Cinnamon S.; Berrettini, Wade H.; Bergen, Andrew W.; Magistretti, Pierre J.; Duvvuri, Vikas; Strober, Michael; Brandt, Harry; Crawford, Steve; Crow, Scott J.; Fichter, Manfred M.; Halmi, Katherine A.; Johnson, Craig; Kaplan, Allan S.; Keel, Pamela K.; Klump, Kelly L.; Mitchell, James E.; Treasure, Janet; Woodside, D. Blake; Marzola, Enrica; Schork, Nicholas J.; Kaye, Walter H.

doi:10.1038/npp.2011.108

Cited by 39 publications

(30 citation statements)

References 60 publications

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“…These regions also did not include genes that have been reported to be associated with anorexia nervosa, such as CTNNA2, CNTNAP2, EPHX2, GABRG1, HTR1D, OPRD1, and PPP3CA (Bloss et al, 2011; Boraska et al, 2014; Scott-Van Zeeland et al, 2014; Wang et al, 2011). This, in combination with the identification of genes in the BD+ED analyses that were not significant in the BDO vs. CTL analysis, suggests that bipolar disorder with eating disorder comorbidity may represent a unique clinical phenotype that is distinct from both bipolar disorder and eating disorders.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region

Study

2016

Journal of Affective Disorders

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Background Bipolar disorder is a heterogeneous mood disorder associated with several important clinical comorbidities, such as eating disorders. This clinical heterogeneity complicates the identification of genetic variants contributing to bipolar susceptibility. Here we investigate comorbidity of eating disorders as a subphenotype of bipolar disorder to identify genetic variation that is common and unique to both disorders. Methods We performed a genome-wide association analysis contrasting 184 bipolar subjects with eating disorder comorbidity against both 1,370 controls and 2,006 subjects with bipolar disorder only from the Bipolar Genome Study (BiGS). Results The most significant genome-wide finding was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT (p=8.9×10−8 for rs4854912) with a secondary peak in the adjacent FXR1 gene (p=1.2×10−6 for rs1805576) on chromosome 3q26.33. This region was also the most prominent finding in the case-only analysis (p=3.5×10−7 and 4.3×10−6, respectively). Several regions of interest containing genes involved in neurodevelopment and neuroprotection processes were also identified. Limitations While our primary finding did not quite reach genome-wide significance, likely due to the relatively limited sample size, these results can be viewed as a replication of a recent study of eating disorders in a large cohort. Conclusions These findings replicate the prior association of SOX2-OT with eating disorders and broadly support the involvement of neurodevelopmental/neuroprotective mechanisms in the pathophysiology of both disorders. They further suggest that different clinical manifestations of bipolar disorder may reflect differential genetic contributions and argue for the utility of clinical subphenotypes in identifying additional molecular pathways leading to illness.

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Section: Discussionmentioning

confidence: 99%

A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region

Study

2016

Journal of Affective Disorders

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“…15 The presence of childhood anxiety disorders predicts more severe ED symptoms, such as lower body mass index (BMI) and more psychopathology 15, 16 and elevated anxiety is associated with poor outcome. 17 …”

Section: Temperament and Personality In Anmentioning

confidence: 99%

Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa

Kaye

Wierenga

Bailer

et al. 2013

Trends in Neurosciences

436

307

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Individuals with anorexia nervosa (AN) engage in relentless, restrictive eating and often become severely emaciated. Because there are no proven treatments, AN has high rates of relapse, chronicity, and death. Those with AN tend to have childhood temperament and personality traits, such as anxiety, obsessions, and perfectionism, which may reflect neurobiological risk factors for developing AN. Restricted eating may be a means of reducing negative mood caused by skewed interactions between serotonin aversive or inhibitory and dopamine reward systems. Brain imaging studies suggest altered eating is a consequence of dysregulated reward, and/or awareness of homeostatic needs, perhaps related to enhanced executive ability to inhibit incentive motivational drives. Understanding the neurobiology of this disorder is likely to be important for developing more effective treatments.

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“…There are multiple ways in which these traits may influence the etiology, maintenance and treatment of the disorder. For example, elevated anxiety and HA not only maintain ED symptoms, but may predict poor treatment outcome; [28, 50–54] and higher levels of pre-meal anxiety predict lower food intake [44]. This is offset through the anxiolytic effect from acute dietary restraint and caloric restriction [44, 55].…”

Section: A Neurobiological Model For Anorexia Nervosamentioning

confidence: 99%

Applying neurobiology to the treatment of adults with anorexia nervosa

et al. 2016

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BackgroundAnorexia nervosa is a severe, biologically based brain disorder with significant medical complications. It is critical that new, effective treatments are developed to interrupt the persistent course of the illness due to the medical and psychological sequelae. Several psychosocial, behavioral and pharmacologic interventions have been investigated in adult anorexia nervosa; however, evidence shows that their impact is weak and treatment effects are generally small.MethodThis paper describes a new neurobiological anorexia nervosa model that shifts focus from solely external influences, such as social and family, to include internal influences that integrate genetic and neurobiological contributions, across the age span. The model serves as a theoretical structure for a new, five-day treatment, outlined in this paper, targeting anorexia nervosa temperament, which integrates neurobiological dimensions into evidence-based treatment interventions. The treatment is in two phases. Phase I is a five day, 40 hour treatment for anorexia nervosa adults. Phase II is the follow-up and is currently being developed.ResultsPreliminary qualitative acceptability data on 37 adults with anorexia nervosa and 60 supports (e.g., spouses, parents, aunts, friends, partners, children of anorexia nervosa adults) are promising from Phase I. Clients with anorexia nervosa and their supports report that learning neurobiological facts improved their understanding of the illness and helped equip them with better tools to manage anorexia nervosa traits and symptoms. In addition, nutritional knowledge changed significantly.ConclusionsThis is the first neurobiologically based, five-day treatment for adults with anorexia nervosa and their supports. It is a new model that outlines underlying genetic and neurobiological contributions to anorexia nervosa that serves as a foundation to treat both traits and symptoms. Preliminary qualitative findings are promising, with both clients and supports reporting that the neurobiological treatment approach helped them better understand the illness, while better conceptualizing how to respond to their traits and manage their symptoms. Data in Phase I shows promise as a neurobiologically based intervention for anorexia nervosa, and it serves as a foundation for the development of Phase II. Evidence of ongoing program efficacy will be described as data are reported on Phase II.Trial registrationNCT NCT02852538 Registered 1 August 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s40337-016-0119-x) contains supplementary material, which is available to authorized users.

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Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs

Cited by 39 publications

References 60 publications

A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region

A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region

Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa

Applying neurobiology to the treatment of adults with anorexia nervosa

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