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Molecular neuroanatomy of anorexia nervosa.

ABSTRACT: 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.

SUBMITTER: Howard D

PROVIDER: S-EPMC7351758 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Molecular neuroanatomy of anorexia nervosa.

Howard Derek D Negraes Priscilla P Voineskos Aristotle N AN Kaplan Allan S AS Muotri Alysson R AR Duvvuri Vikas V French Leon L

Scientific reports 20200710 1

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 ...[more]

PMID: 32651428

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Project description:BackgroundAdolescence is a critical developmental period for the study of anorexia nervosa (AN), an illness characterized by extreme restriction of food intake. The maturation of the reward system during adolescence combined with recent neurobiological models of AN led to the hypothesis that early on in illness, restrictive food choices would be associated with activity in nucleus accumbens reward regions, rather than caudate regions identified among adults with AN.MethodsHealthy adolescents (HC, n = 41) and adolescents with AN or atypical AN (atypAN, n = 76) completed a Food Choice Task during fMRI scanning. Selection of high-fat foods and choice-related activation in nucleus accumbens and anterior caudate regions-of-interest (ROIs) were compared between individuals with AN/atypAN and HC. Associations were examined between choice-related activation and choice preferences among the AN group. Exploratory analyses examined associations between choice-related activation and psychological assessments among the patient group.ResultsAdolescents with AN or atypAN selected fewer high-fat foods than HC (t = -5.92, p < .001). Counter to predictions, there were no significant group differences in choice-related activation in the ROIs. Among individuals with AN or atypAN, choice-related neural activity in the anterior caudate was significantly negatively associated with high-fat food selections in the task (r = -.32, p = .024). In exploratory analyses, choice-related anterior caudate activation was positively associated with psychological measures of illness severity among patients (p's < .05, uncorrected).ConclusionsIn this large cohort of adolescents with AN/atypAN, there was no evidence of altered reward system engagement during food choice. While there was no group difference in choice-related caudate activation, the associations with choices and psychological measures continue to suggest that this neural region is implicated in illness. Longitudinal analyses will clarify whether neural variability relates to longer-term course.

Project description:IntroductionSleep is crucial for physical and psychological health, and disturbances are closely linked to psychiatric disorders, making their management essential for improving treatment outcomes and preventing relapse. Although sleep disturbances are implicated in psychopathology of eating disorders, its role in anorexia nervosa (AN) remains unclear. This review aimed to characterise sleep in AN.MethodsA systematic search was conducted in four scientific databases, including papers from inception to 25 May 2024. A machine learning algorithm (ASReview) was utilised to screen titles and abstracts for eligibility. Sleep quantity, architecture, and quality were investigated. Meta-analyses were conducted to investigate the difference between patients with AN and healthy controls (HC) in total sleep time (TST), wake after sleep onset (WASO), sleep onset latency (SOL), sleep efficiency, Sleep Stage 1, 2, slow wave sleep, rapid eye movement (REM) sleep and REM latency. Certainty of evidence was assessed using the GRADE approach.ResultsOut of 67 potentially eligible papers, 31 were included in this review, with 15 in the meta-analyses. Statistically significant average mean differences were found for TST (-32.1 min [95% CI: -50.9, -13.4]), WASO (19.0 min [95% CI: -2.4, 40.3]), and sleep efficiency (-4.4% [95% CI: -7.9, -0.9]). Additionally, Sleep stage 1 was significantly increased (2.4% [95%-CI: 0.05, 4.7]), while REM sleep was reduced (-2.1% [95%-CI: -4.2, -0.02]). Subgroup analysis showed that TST and WASO did not improve significantly after weight restoration.ConclusionSleep in patients with AN is impaired, with lower TST and sleep efficiency, higher WASO, more time in stage 1 sleep, and less in REM. Weight restoration alone may not improve sleep. While more research is needed, substantial accompanying sleep disturbances in AN justifies addressing these in current treatment practice, also because of the chronic character of AN and importance of sleep for long term (mental) health.

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Molecular neuroanatomy of anorexia nervosa.

Publications

Molecular neuroanatomy of anorexia nervosa.

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