Andrea B. Goldschmidt, Ph.D. - US grants

? DESCRIPTION (provided by applicant): Loss of control (LOC) while eating (i.e., the sense that one cannot control what or how much one is eating) is prevalent among children and adolescents. LOC eating is associated with a range of physical and psychosocial health impairments, including obesity and the development of partial- and full-syndrome eating disorders. Early identification is thus critical for preventing or minimizing these adverse health outcomes. However, little is known about the development of LOC eating in children and, consequently, there is a paucity of effective interventions. Impairments in emotion regulation appear to be involved in the onset and maintenance of eating pathology in obese samples. To date, emotion regulation in youth with LOC eating problems is poorly understood, and research on underlying neurodevelopmental substrates is virtually nonexistent. The proposed research aims to characterize neurocircuitry involved in emotion regulation among 30 overweight children with LOC eating as compared to 30 overweight and 15 normal-weight controls without LOC. Participants will complete a cognitive reappraisal task whilst situated in an MRI scanner, the purpose of which is to characterize neural activity involved in reappraisal versus an emotion maintenance control condition. The proposed research aims to advance the field's understanding of the nature and correlates of LOC eating in overweight children so as to inform intervention development. The research also fits within the broader context of the applicant's career development goals. The candidate is an Assistant Professor of Psychiatry and Behavioral Neuroscience whose research program has focused on pediatric eating and weight disorders, particularly binge eating and its relationship with negative affect. The overarching goal of the 4-year training program is to establish the candidate as an independent investigator. Specific training activities will focus on gaining a sufficient understanding of neurocircuitry involved in emotion regulation across childhood and adolescence to be able to utilize a developmental neuroscience framework for the probing of dysregulated eating; and obtaining experience collecting, analyzing, and interpreting fMRI data. The mentorship team consists of internationally-known experts in developmental psychopathology, affective neuroscience, and pediatric eating and weight disorders who will provide conceptual oversight of the training plan and nurture the applicant's career trajectory. Research and training activities will be carried out at the University of Chicago's Department of Psychiatry and Behavioral Neuroscience and Brain Imaging Research Center. This Career Development Award will fill gaps in the candidate's training in order to broaden her expertise in pediatric obesity and eating disorders, ultimately guiding the research program towards the development of novel interventions for these problems, and facilitating her transition into an independent clinical investigator.

PROJECT SUMMARY/ABSTRACT Insufficient sleep and excess weight status contribute to adverse health outcomes across the lifespan, including risk for cardiometabolic disease. Cross-sectional data suggest that children with overweight/obesity are more likely to experience sleep disturbances than their non-overweight peers. Although the nature of this association may be bidirectional, prospective studies indicate that sleep impacts body weight regulation through multiple physiological and psychological pathways. In particular, insufficient sleep is related to greater energy intake and reduced diet quality in children. Although mechanisms explaining the association between sleep and eating behavior are poorly understood, sleep restriction has been found to impact brain processes related to reward valuation of food and self-regulation, the behavioral manifestations of which may increase susceptibility to suboptimal dietary behaviors and subsequent weight gain. A limitation of prior research on mechanisms is that much of it has been conducted in adults and in laboratory settings, thereby calling into question the ecological validity of the findings. Alternatively, studies on sleep restriction/extension in children?s natural environments have relied on retrospective reporting of eating behavior, included children across the weight spectrum, and had limited focus on underlying mechanisms, particularly neural substrates. A clearer understanding of momentary mechanisms involved in the sleep/eating association could improve development and/or refinement of sleep-related interventions, particularly those delivered in real time when risk for engaging in maladaptive eating is highest. The proposed R01 study will examine prospective associations among sleep, eating-related self-regulation, and eating behavior in the natural environment. Community-based children with overweight or obesity (n=120) will undergo a naturalistic protocol involving assessment of typical sleep and eating patterns (week 1), followed by sleep restriction or extension (weeks 2 and 3, separated by a 7-day wash-out), the latter occurring within a randomized crossover design. Assessment throughout the study period will involve daily actigraphy measurement of sleep patterns; repeated daily self-reports on eating behavior and behavioral assessment of eating-related self-regulation; and intermittent 24-hour dietary recalls informed by daily real-time food photography. Participants will complete fMRI-based assessment of neural activation during an eating-related self-regulation task after each week-long period of sleep restriction and extension. Overall aims are to assess short-term effects of sleep extension versus restriction on eating-related self-regulation (including behavioral and neural performance) and naturalistic eating behavior. These data will clarify timing and trajectory of changes in eating behavior and self-regulatory mechanisms as a consequence of sleep patterns. The proposed study has clear potential to advance scientific and clinical understanding of mechanisms involved in the prospective associations between inadequate sleep and maladaptive eating in youth and inform interventions to alleviate their cumulative personal and societal burden.

PROJECT SUMMARY/ABSTRACT Pediatric overweight and obesity continue to be major public health issues. Loss of control (LOC) eating is an obesity-related phenotype that affects approximately 30% of children and adolescents with overweight/obesity and may impede successful weight control. Both pediatric overweight/obesity and LOC eating are associated with relative deficiencies in executive functioning. In particular, our recently published data suggest that youth with LOC eating and concomitant overweight/obesity have poorer working memory (WM) than their overweight/obese and non-overweight peers. These decrements may inhibit their abilities to adaptively respond to environmental and internal cues related to eating. A limitation of prior research is that it has largely focused on individual differences in neurocognitive processes, thereby failing to inform our understanding of how these processes may drive eating behavior on a moment-to-moment basis and limiting development of interventions that can be delivered in real time when individuals are most at risk for engaging in LOC eating. This R03 application proposes to use ecological momentary assessment (EMA) and validated dietary assessment (Nutritional Database System for Research; NDSR) to assess eating behavior in the context of acute WM, and assess whether fluctuations in WM are related to LOC eating or excess energy intake in children (10-17 years) with LOC eating and overweight/obesity relative to their overweight/obese and non- overweight peers. The applicant is a current K23 recipient (DK-105234) whose program of research has focused on clarifying the etiology and maintenance of LOC eating in youth with overweight/obesity. The applicant's expertise in momentary assessment of affective and neurocognitive processes underlying eating- and weight-related disorders forms the basis of the current proposal. In particular, the applicant has extensive experience utilizing EMA to understand antecedents and consequences of maladaptive eating in near real time in the natural environment. EMA is ideal for investigating eating behavior in the context of WM as it allows for prospective, momentary assessment of within- and between-person variables of interest. In the proposed study, participants will monitor their eating behavior via EMA for 14 days, and dietary recalls completed on 3 randomly selected days during this same period. They will also complete EMA tasks of numerical and spatial WM. Data on potential covariates (e.g., mood) will also be collected via EMA. These data will clarify timing and trajectory of LOC eating and dietary intake in relation to WM performance. This study, which is the first to use EMA to clarify if momentary WM performance is related to eating behavior, has clear potential to advance scientific and clinical understanding of mechanisms that promote the occurrence of maladaptive eating in youth and inform interventions to alleviate their cumulative personal and societal burden. Furthermore, this proposal provides a clear pathway to independence for the investigator, and will enable her to pursue future R01 funding to understand the impact of WM training on eating- and weight-related outcomes.

PROJECT SUMMARY/ABSTRACT Pediatric overweight and obesity continue to be major public health issues. Loss of control (LOC) eating is an obesity-related phenotype that affects approximately 30% of children and adolescents with overweight/obesity and may impede successful weight control. Pediatric overweight/obesity and LOC eating frequently emerge during childhood and adolescence, and tend to follow a chronic and unremitting course if untreated. Both conditions are associated with relative deficiencies in executive functioning (EF), including working memory, planning, inhibitory control, and decision-making. These decrements may impair one?s ability to appropriately regulate weight and eating behavior. A limitation of prior research is that it has been primarily cross-sectional in nature, which inhibits understanding of the timing and direction of influence involved in the associations among EF, weight change, and eating pathology. Moreover, little is known about the domain specificity of relative EF deficits in youth with overweight/obesity and LOC eating, nor about their underlying neural substrates. An improved understanding of the nature and prospective outcomes of EF impairments in youth with overweight/obesity and LOC eating could inform intervention development by indicating whether treatments should focus on improving general and/or food-specific EF, as well as which neural pathways should be targeted to achieve the most robust and sustained effects on eating and weight. The proposed R01 study will examine prospective associations between EF performance and related neural substrates, and child weight change and LOC eating. Community-based children representing a spectrum of risk, including non- overweight/obese (n=60), overweight/obese (n=60), and overweight/obese with comorbid LOC eating (n=60), will provide repeated assessments of height/weight, LOC eating pathology, and general and food-specific EF every 6-12 months over 2 years of follow-up. A subset of participants from each risk category will complete a baseline and 18-month fMRI protocol assessing neural substrates of general and food-specific working memory. Specific aims are to investigate prospective associations between both general and food-specific EF, and their neural substrates, and trajectories of weight change and LOC eating (including remittance and persistence) over 2 years. These data will clarify timing and trajectory of weight change and LOC eating in relation to EF performance and its associated neural activation patterns. This study, which is the first to prospectively examine associations among general and food-specific EF, weight trajectories, and LOC eating, has clear potential to advance scientific and clinical understanding of mechanisms that promote the onset and maintenance of maladaptive eating in youth and inform interventions to alleviate their cumulative personal and societal burden. Furthermore, this application builds on the principal investigator?s programmatic line of research on neurocognitive factors involved in eating- and weight-related problems, and provides a clear pathway to future clinically and scientifically impactful studies.

PROJECT SUMMARY/ABSTRACT Anorexia nervosa (AN) is a serious psychiatric illness that affects ~1% of adolescents and is associated with high rates of morbidity and mortality. Family-based treatment (FBT), which involves empowering caregivers to take control of refeeding to restore the adolescent to a normative weight and eating trajectory, is postulated to operate via increasing caregiver self-efficacy related to refeeding, and decreasing adolescent distress through repeated exposure to eating- and weight-related stimuli. Although FBT is currently considered the ?first line? treatment for adolescent AN, it is underutilized in community settings and is unavailable to many families for a multitude of practical reasons (e.g., costs of treatment, limited availability of trained providers in many regions of the country), particularly those from underrepresented sociodemographic groups. Furthermore, a substantial subset of families do not optimally respond to FBT, which may be due to failure of newly acquired intervention skills to generalize outside of the (typically office-based) treatment context. Home-based treatment is an alternative to traditional office-based outpatient treatment that can reduce many pragmatic barriers to treatment uptake and engagement, and may enhance generalizability of treatment skills as it is delivered in multiple naturalistic settings where refeeding often occurs (e.g., home, school, community). Although home-based models have been successfully applied to other psychiatric conditions, home-based treatments for AN have never been tested. Moreover, FBT has undergone limited investigation in ?real world? settings outside of specialty academic and clinical environments dedicated to eating disorders. As a result, much of what is known about FBT is based on relatively homogeneous samples with limited representation from individuals from lower income and racial/ethnic minority backgrounds. Furthermore, it is unclear if putative FBT mechanisms apply in the effectiveness context. The proposed R34 pilot effectiveness trial will assess outcomes, implementation, and mechanisms of FBT for adolescent AN adapted for the home setting (FBT-HB), delivered in the context of two community-based behavioral health agencies that serve a primarily lower-income, racially and ethnically diverse clientele. Adolescents with AN-spectrum disorders (n=50) and their caregivers will be randomly assigned to either FBT-HB or home-based usual care (integrated family therapy approach). Caregivers and adolescents will provide data on weight, eating, and putative treatment mechanisms, including caregiver self- efficacy, adolescent distress, and generalizability of treatment skills. Implementation constructs will be measured among providers and participating families. Overall aims are to assess preliminary effects of FBT- HB on adolescent eating and weight outcomes; FBT-HB acceptability, appropriateness, feasibility, and fidelity; and caregiver- and adolescent-level mechanisms of change. The proposed study has clear potential to advance scientific and clinical understanding of the real-world effectiveness of FBT for AN, including whether adapting it for the home setting may improve its accessibility and effects on treatment outcome.