Tom Hildebrandt

Objective: Numerous publications utilize data from the Adolescent Brain and Cognitive Development (ABCD) Study. This review aimed to evaluate how data from the ABCD cohort contributes to understanding the pathophysiology of incipient eating disorders. Method: Searches were completed using PubMed and the ABCD Study research publications database. All available neuroimaging articles assessing prevalence and predictors of disordered eating/eating disorders were included. Results: Thirty‐eight articles met inclusion criteria, 10 of which presented neuroimaging results, all analyzing baseline brain data. The majority ( n = 9) assessed brain structure and function in children with binge eating (BE)/binge eating disorder (BED). Results were inconsistent across imaging modalities. Structural MRI studies included widespread increases in gray matter density and reductions in cortical thickness associated with eating pathology. Task‐based fMRI studies reported conflicting findings, with frontostriatal activation during reward processing in children with BE/BED reduced, increased, or not different compared to controls. Resting‐state fMRI analyses consistently identified reduced functional connectivity in key frontal circuits, although patterns differed when samples were stratified by sex or BMI. Non‐imaging studies showed positive associations between eating disorders/disordered eating and several sociodemographic, cognitive, behavioral, and biological correlates. Discussion: Alterations in brain structure and function associated with binge eating are identified in neuroimaging analyses of baseline scans from the ABCD cohort, with inconsistent results. One potential pattern suggests alterations in reward system function, although the direction and exact location of such alterations are unclear. Consistency in methodological approaches is necessary to allow patterns in neural alterations to be more clearly identified. There is significant and ongoing potential for the ABCD Study dataset to quantify developmental aspects of binge eating. Recommendations for future analyses as the sample progresses through puberty and eating disorder prevalence increases are also presented.

Background: Alzheimer’s disease (AD) exhibits sex differences in pathology and cognitive trajectories. Understanding how these differences manifest across the Alzheimer’s continuum can improve early detection, diagnostics, and interventions. We examined sex differences in the association between cerebrospinal fluid (CSF) pTau181/Aβ42 ratio changes and verbal memory decline across the preclinical and mild cognitive impairment (MCI) stages of AD. Methods: In this retrospective, longitudinal, observational study, data were extracted from 401 participants (age range: 55-87.8, 98% non-Hispanic White) of the Alzheimer’s Disease Neuroimaging Initiative cohort study who were classified as either preclinical AD (78 females, 73 males) or MCI (104 females, 146 males) at baseline and had CSF pTau181/Aβ42 ratio and cognitive assessment data at at-least two timepoints. Using regression models, we examined the relationship between changes in CSF pTau181/Aβ42 and verbal memory across all available time points and the moderating role of sex and AD stage over a mean follow-up period of 4 years. Verbal memory was represented by a composite z-score averaging Learning and Delayed Recall z-scores of the Rey Auditory Verbal Learning Test. Covariates included baseline age, education, and apolipoprotein E genotype. Results: A significant sex * diagnostic group * biomarker change interaction ( b =-17.47, 95%CI = 27.60 to -7.33, p = .001) indicated that sex differences in the relationship between changes in CSF pTau181/Aβ42 ratio and verbal memory differed by disease stage. While males in the preclinical AD stage showed steeper memory decline than females with increasing pTau181/Aβ42 ratios, this difference was not statistically significant. In contrast, in the MCI stage, a significant sex * biomarker change interaction ( b = 10.17, 95% CI = 4.94 to 15.40, p < .001) indicated that females exhibited significantly steeper memory decline associated with increasing pTau181/Aβ42 ratios compared to males. Conclusion: Sex differences in the relationship between AD biomarker levels and cognitive decline vary by disease stage. Although not statistically significant, females demonstrated resilience to memory decline in the preclinical stage, whereas, in the MCI stage, they experienced significantly steeper memory loss compared to males. Results suggest that accounting for sex in biomarker-based methods of disease detection and tracking can improve early detection and intervention in both sexes.

Background: Understanding the emotional context of feeding behavior may help identify causal mechanisms of food avoidance among individuals with anorexia nervosa. Although predominant food avoidance models assume fear of fat drives feeding behavior, disgust may be more theoretically and proximally relevant to moment‐to‐moment experiences of feeding. This study, therefore, aimed to examine affect and food avoidance using automated affect analysis from facial response by measuring time‐specific transitions in disgust during a laboratory eating paradigm. We hypothesized that phase transitions in disgust would distinguish temporally self‐initiated eating from food avoidance.Methods: Sixty‐three adolescents with anorexia nervosa or another low‐weight eating disorder (LWED) and 27 age‐ and sex‐matched controls were recruited as part of a larger study; 45 patients and 22 controls provided data on autonomous eating and facial affect during a laboratory meal. Dynamic structural equation models quantified moment‐to‐moment relationships between disgust and feeding behavior.Results: Self‐initiated eating was associated with greater increases in disgust, but not fear, intensity among those with LWED relative to control participants and greater disgust intensity predicted lower likelihood of self‐initiated eating.Discussion: Phasic transitions in disgust provide moment‐to‐moment evidence of affective influence on self‐initiated eating and lend credibility to the hypothesis that disgust contributes to food avoidance and initiation in individuals with LWED.

Objective: Conventional randomized controlled trials (RCTs) have long served as the foundation of research in clinical psychology; however, most treatments for eating disorders show only modest effects on reduction of symptoms and maintenance of long‐term remission. New options for psychotherapy treatment development research, beyond continuing to pursue additive or subpopulation approaches, are needed.Methods: One option is to apply dose–response designs, which are commonplace in studies of pharmacology, toxicology, and medical research, and characterized by the evaluation of the amount of exposure (dose) to an intervention, and the resulting changes in body function or health (response).Results: Eating disorder interventions are particularly well‐suited for dose–response treatment designs. The deadly nature of eating disorders makes it imperative that patients are not turned away for not being “ready” to engage with treatment. By identifying optimal doses, research will likely yield a more parsimonious course of treatment, which will lend itself to reduced costs, greater uptake, and reduced drop‐out.Discussion: Limited use of within‐subject designs in trials for patients with eating disorders has produced fast‐track efficacy studies and omitted key elements in the treatment development pathway. To decrease reliance on RCT's, dose–response methods should be applied as an alternative study design.Public Significance: Eating disorders are associated with medical and psychiatric comorbidities, poor quality of life, and high mortality. Access to evidence‐based services for patients with eating disorders is limited, and identifying additional effective treatment options can be difficult because of challenges inherent to randomized‐controlled trials. This manuscript describes an alternative trial methodology to maximize the information that can be gathered prior to utilizing a standard large‐scale efficacy design.