Dataset Information

Developmental stage-dependent relationships between ghrelin levels and hippocampal white matter connections in low-weight anorexia nervosa and atypical anorexia nervosa.

ABSTRACT:

Introduction

Disruptions in homeostatic and hedonic food motivation are proposed to underlie anorexia nervosa (AN) and atypical AN, restrictive eating disorders which commonly onset in puberty. Ghrelin, a neuroprotective hormone that drives hedonic eating is increased in AN and is expressed in the hippocampus. White matter (WM) undergoes significant change during puberty in regions involved in food motivation, particularly WM tracts connected with the hippocampus. The association between ghrelin and WM region of interest (ROI) with hippocampal connections in restrictive eating disorders, particularly in adolescence during key neurodevelopmental growth, is unknown.

Methods

We evaluated fasting plasma ghrelin and WM microstructure (measured by free-water corrected fractional anisotropy (FA-t)) in WM ROIs with hippocampal connections - the fornix and the hippocampal portion of the cingulum - in 56 adolescent females (age range: 11.9 - 22.1 y; mean: 19.0 y) with low-weight eating disorders including AN and atypical AN (N = 36) and healthy controls (N = 20).

Results

FA-t in the fornix or hippocampal portion of the fornix did not differ between groups. Ghrelin was higher in AN/atypical AN vs. HC and was positively correlated with puberty stage in the AN/atypical AN group, but not the HC group. The correlation between ghrelin and FA-t in the fornix was significantly different in females with AN/atypical AN compared to controls. In AN/atypical AN, pubertal stage moderated the relation between fasting plasma ghrelin and FA-t in the fornix: higher fasting ghrelin was associated with lower FA-t in the fornix in late-post-puberty, but was not associated with FA-t in the early to mid stages of puberty.

Conclusions

In post-pubertal females with low-weight AN/atypical AN, higher levels of ghrelin are associated with lower FA-t in the fornix. This relationship is not evident in the early to mid stages of puberty in AN/atypical AN or in HC, and may reflect a lack of possible neuroprotective effects of ghrelin in late-post puberty only. Understanding the effects of ghrelin on WM microstructure longitudinally and following recovery from AN/Atypical AN and how this differs across pubertal stages will be an important next step. These findings could ultimately inform treatment staging and aid in diagnosis and detection of AN/atypical AN.

SUBMITTER: Breithaupt L

PROVIDER: S-EPMC8629489 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportancePeople with anorexia nervosa often experience difficulties regulating their emotions. There is no longitudinal evidence as to whether these differences are already present in childhood or when they begin to emerge.ObjectiveTo investigate the association between emotion regulation trajectories from 3 to 7 years of age and symptoms of anorexia nervosa and atypical anorexia nervosa in adolescence.Design, setting, and participantsThis cohort study included all children with complete exposure data in the Millennium Cohort Study, a UK general population birth cohort. Data were acquired from June 2001 to March 2016 and analyzed from June to November 2020.ExposuresMothers reported on their children's emotion regulation skills at 3, 5, and 7 years of age using the Children's Social Behavior Questionnaire. Multilevel models were used to derive early childhood emotion regulation scores (ie, predicted intercept) and within-child changes in emotion regulation scores from 3 to 7 years of age (ie, predicted slope).Main outcome and measuresSymptoms consistent with a DSM-5 diagnosis of anorexia nervosa or atypical anorexia nervosa at 14 years of age, defined using a range of questions relative to body image, weight perception, and dieting behaviors (hereinafter referred to as broad anorexia nervosa). Univariable and multivariable logistic regression models tested the association between exposures and outcome. Regression models were adjusted for child and family sociodemographic and socioeconomic characteristics and mental health difficulties, prenatal and perinatal factors, child's cognitive development, and maternal attachment.ResultsA total of 15 896 participants (85.7% of total sample; 51.0% boys; 84.5% White individuals) had complete data on the exposure and were included in the main analyses. Among those with complete exposure and outcome data (9912 of the analytical sample [62.4%]), 97 participants (1.0%; 86 [88.7%] girls and 85 [87.6%] White individuals) had symptoms consistent with a diagnosis of broad anorexia nervosa at 14 years of age. No evidence suggested that children with lower emotion regulation ability at 3 years of age had greater odds of later reporting symptoms of broad anorexia nervosa (odds ratio [OR], 1.21; 95% CI, 0.91-1.63). However, children whose emotion regulation skills did not improve over childhood and who had greater problems regulating emotions at 7 years of age had higher odds of having broad anorexia nervosa at 14 years of age (OR, 1.45; 95% CI, 1.16-1.83).Conclusions and relevanceThese findings suggest that difficulties in developing age-appropriate emotion regulation skills in childhood are associated with experiencing broad anorexia nervosa in adolescence. Interventions to support the development of emotion regulation skills across childhood may help reduce the incidence of anorexia nervosa.