Leonard H. Epstein - US grants

Obese children are at an increased risk of becoming obese adults in comparison to their leaner peers. In addition, parental weight greatly increases the risk of becoming a heavy adult. A heavy child with a heavy parent is 2.5 times as likely of becoming an obese adult as a heavy child with thin parents. This proposal is designed to study factors that may contribute to this increased risk. These factors incluce child eating and exercise patterns, parent-child interaction patterns, food preferences, modeling and parent self-efficacy. The proposed study is a randomized controlled outcome evaluation of family-based treatment procedures in obese children with thin or heavy parents. Obese children will be stratified according to parent weight and then randomized to treatment or control group. Families will either be provided a 12 week general health education program or a parent management program focusing on changing eating and exercise habits. After this phase of treatment, children will be seen at months 6, 12 and 24 for follow-up. It is predicted that parents and obese children in families with thin or heavy parents will differ in their eating and activity patterns, their interaction patterns, and parental self-efficacy. In addition, it is predicted that children provided treatment will do better than controls over the 24 months of observation, and there will be an interaction of treatment with parent weight, so that children with thin parents will do better than children with obese parents.

The proposed study is designed to determine the effects of including mastery criteria for teaching eating and exercise behavior change as part of a family-based treatment program for childhood obesity. Behavioral programs for childhood obesity specify the target behavior to be changed and arrange reinforcement contingencies for these changes. However, there is still considerable variability in the extent to which children learn these new eating and exercise behaviors, and consequently considerable variability in the weight losses achieved. This study assesses the effects of introducing mastery criteria, in which a child and parent will progress through the program at the rate he/she has mastered the material, and demonstrated the desired behavior change. This Paced/Mastery program will be compared to a fixed-pace/Non-mastery Control group, which constitutes the conventional treatment protocol, and a Paced/Yoked Control group, in which progress through the program is dependent on the progress of a child or parent in the Paced/Mastery group. It is predicted that children and their parents that are provided with mastery criteria will show better learning and retention of the written material and the behavioral skills than subjects in the two control groups. In addition, weight losses in the three groups should be different, with the weight changes showing the same pattern of results as the behavioral skills.

Drugs such as cocaine, the opiates and nicotine lose much of their effectiveness--that is, show tolerance--after repeated administration. It was once thought that the development of drug tolerance depended exclusively only on exposure to the drug. However, it is now quite clear that learned associations with the environmental conditions within which drugs are taken, referred to as drug-related cues, can greatly influence this tolerance process. Dr. Caggiula and his colleagues have recently demonstrated that tolerance to both the analgesic and appetite- suppressant effects of nicotine are strongly influenced by learned associations with environmental cues signaling drug delivery. Administering the drug in the absence of these cues reverses the tolerance, and, renders the drug significantly more effective. Dr. Caggiula is now extending and complementing this work with more detailed learning analyses. The first series of studies focuses on pharmacological and learning variables that control the maintenance of tolerance, using rats that had previously been made tolerant to the anorectic effects of nicotine. The second series of experiments are investigating which factors that are responsible for the development of tolerance in drug-naive rats.

Obese children choose to be sedentary rather than active, and sedentary behaviors influence weight control since they compete with being active, and set the occasion for excess caloric intake. We recently demonstrated that reinforcing children for reducing sedentary behaviors resulted in superior weight control compared to children who were reinforced for being active, or reinforced for the combination of increasing active and reducing sedentary behaviors. All children showed similar improvements in fitness. Preference for being active was increased the most for children who were reinforced for reducing their sedentary behavior. These results suggest the relevance of targeting sedentary behaviors to improve childhood weight control. The proposed clinical and laboratory studies are designed to understand factors that influence the choice of sedentary versus active alternatives. The clinical outcome study assesses the parameters of the changes in sedentary or active behaviors associated with superior weight control observed when a decrease in sedentary behaviors rather than an increase in active behaviors is reinforced. Obese children will be randomized to one of four groups who are provided our standard family- based behavioral treatment program, varying the amount of leisure time sedentary behaviors allowed or the amount of exercise prescribed. Activity patterns, activity preference, intake, laboratory assessment of the relative reinforcing value of vigorous or sedentary activity and measures of decisional balance and perception of choice will be measured to understand how these variables influence weight change. The three laboratory studies provide direct tests of mechanisms for the clinical phenomena we have identified. The first study tests the importance of reinforcing a decrease in sedentary behaviors versus an increase in active behaviors; the second study tests the importance of targeting high or low preference sedentary behaviors; and the third study tests three alternative ways to decrease sedentary behavior. In each study free choice for active or sedentary alternatives will be assessed before and after multiple days in which the experimental procedures have been in effect.

DESCRIPTION (Taken from application) Obesity is an increasingly prevalent problem in childhood. There is a public health need to disseminate empirically validated treatments for childhood obesity. This proposal is designed to evaluated alternative methods for delivery of a family-based behavioral intervention for an empirically validated treatment of obesity in 8-12 year-old children and their parents. The family-based treatment was designed to maximize efficacy, and includes small groups, didactic teaching, and individual attention that is too labor intensive for widespread clinical and public health use. One of the first steps in development of an intervention for widespread dissemination would be to test a program that can be delivered to families in a more cost effective manner. Previous obesity studies have demonstrated that treatment outcome does not depend upon the intensity of therapist involvement. Research has demonstrated the efficacy and cost- effectiveness of non-didactic, large group interventions for child problems. The present study adapts the large group intervention to obesity treatment. The proposed experiment compares sixty obese children randomized to one of three groups: small group, individualized treatment: large group, non-individualized treatment, and non-treatment control. The primary outcome is the comparisons of changes in percent overweight between the three groups. This study provides the first experimental test of different methods for implementing family-based behavioral interventions for obese children.

DESCRIPTION: (Applicant's Description) Nicotine is a powerful addictive drug, and cessation is complicated by the positively and negatively effects of nicotine. The decision to stop smoking involves choosing a delayed positive benefit, improved health, over the immediately reinforcing effects of smoking. Research on other drugs of abuse has shown that drug abusers discount future positive benefits in relationship to current alternatives more than non-drug abusers, and this phenomena has recently been extended to smokers. This grant is designed to evaluate factors that may increase the reinforcing value of smoking, and thus increase the discounting of future benefits of not smoking. The first study is designed to examine the dose-response relationship between nicotine deprivation and discounting contrasting no deprivation with 24, 48 and 96 hours of deprivation. In the second study we will examine the relationship between nicotine dependence and discounting in three groups, chippers, light and heavy smokers, with the prediction that heavy smokers will discount future rewards at higher rates than light smokers, and light smokers will discount more than chippers. In addition, we will relate the absolute reinforcing value of smoking, as determined from responding on progressive ratio schedules of reinforcement, to discounting, with the prediction that thc higher the reinforcing value of smoking, the greater the rate of discounting future benefits. These studies are designed to identify determinants of discounting in smokers, and will provide a better understanding of factors that may be important for maintaining cessation.

DESCRIPTION: (adapted from Investigator's abstract) Food is a powerful primary and secondary reinforcer, and obese persons find food more reinforcing than nonobese persons. In addition, obese persons may find alternatives to food less reinforcing than nonobese persons, providing a mechanism to understand why obese persons consume excess calories. The food deprivation that is associated with a calorie reduced diet may increase the reinforcing value of food, paradoxically making it more difficult for some obese persons to maintain the decreased caloric levels needed for weight loss and maintenance. This study is designed to test an innovative program for pediatric obesity based on behavioral economic theory that provides reinforcement for obese children for alternatives to their usual high-fat/low nutrient density eating, reduces access to intake of high-fat foods, and teaches parents to reduce behaviors that may increase the reinforcing value of high-fat foods. One hundred twenty obese children will be randomized to one of two groups, an innovative experimental treatment based on behavioral economic principles, and our standard family-based behavioral intervention program. Children will be followed through 2 years after randomization. Dependent measures will include body mass index, changes in percent overweight, changes in the eating and activity environment, parent control and restriction of food intake, child perception of dietary restriction, caloric and nutrient intake, physical activity, and the reinforcing value of noneating alternatives to high-preference, palatable high-fat/low nutrient density foods. This study will yield important information on new ways to treat pediatric obesity, minimizing dietary restriction and maximizing children learning healthier eating habits.

DESCRIPTION (investigator's abstract): The increases in sedentary behaviors such as watching television, VCR and playing video games, have been associated with the increase in prevalence of pediatric obesity. Controlled laboratory and clinical research have shown that reducing these sedentary behaviors is associated with reduction in percent overweight in those who are obese and prevention of development of obesity in those at risk. The mechanisms for how reducing sedentary behaviors, including increased time to be physically active, reduced exposure to television advertising for high-fat, low nutrient density foods, and reduced exposure to cues associated with sedentary behaviors that prompt eating. The aim of this study is to provide detailed information on the influence of changes in physical activity and eating as a function of changes in targeted sedentary behaviors in obese children using an innovative within subject reversal design. Forty six obese children will be studied across three phases. The first phase will be a four-week baseline phase, designed to determine usual sedentary behavior. There will then be two four-week phases designed to increase and decrease sedentary behavior relative to baseline. We hypothesize that reducing sedentary behaviors will result in an increase in physical activity and a reduction in caloric intake in comparison to baseline, and physical activity will be reduced and caloric intake increased relative to baseline when sedentary behaviors are increased above baseline. Moreover, we hypothesize that the process of substitutability of active for sedentary behaviors will be related to the base rates of the targeted sedentary behaviors in relationship to physical activity. Likewise, changes in eating behavior as a function of changing sedentary behaviors will be related to the how often eating is associated with the targeted sedentary behaviors.

DESCRIPTION (provided by applicant): Television, computer games and the internet are common components of the home environments of most children. Sedentary behaviors such as watching television and movies and playing video games are associated with the increased prevalence of pediatric obesity. Controlled laboratory and clinical research has shown that reducing these sedentary behaviors is associated with reductions in percent overweight in those who are obese and decrease in rate of BMI increase in non-obese children. There has been no research designed to test the influence of reducing television watching and other sedentary behaviors on prevention of obesity or further weight gain in overweight or obese youth. The aim of this study is to test an innovative environmental intervention designed to modify the home television watching and computer game use environment in contrast to a control condition. Seventy-two overweight or obese 4-7 year-old boys and girls will be randomized to an environmental intervention that focuses on reduction of television and home movie watching and computer games versus a control intervention. The environmental intervention is designed to gradually reduce targeted sedentary behaviors to 50% of baseline levels. We hypothesize that reducing sedentary behaviors will result in a stabilization or smaller increase in BMI in comparison to an untreated control group followed over two years. In addition, we predict lower energy intake for those in the intervention versus control groups, and an increase in physical activity when sedentary behaviors are decreased for the intervention group, and a further decrease in physical activity as the children in the control group become older. We also predict that children who often eat in association with targeted sedentary behaviors will show the largest decreases in energy consumed when sedentary behavior is decreased, and that children with a high baserate of targeted sedentary behaviors and low baserate of physical activity will be more likely to increase physical activity when sedentary behaviors are reduced.

DESCRIPTION (provided by applicant): One of the basic properties of the nervous system to repeated stimulation is habituation. Eating involves the repeated presentation of food cues, which should lead to habituation. Basic animal and human research has shown that a variety of responses related to eating habituate over repeated food presentations. The habituated response can be dishabituated by presentation of novel food or by presenting an environmental event that requires allocation of processing resources. Habituation may help understand why food variety, and stimuli such as television watching are associated with increases in intake. All of the research with humans to date has been done with adults. The purpose of this grant is to extend this research to children. Six experiments are proposed in the grant. The first two experiments evaluate novel food and food variety as factors that influence habituation to repeated food cues. Experiments 3-5 evaluate the influence of non-food stimuli on habituation to food cues. Experiment 3 assesses differences in allocation of processing resources by comparing controlled and automatic search tasks on habituation. Experiments 4 and 5 assess the influence of two common distractors during eating on habituation, watching videos and reading. Experiment 6 evaluates whether food variety has similar effects on salivary habituation and changes in motivated responding to obtain and consume food. These studies will provide a theoretical basis for oral habituation and eating in children, and may provide behavioral mechanisms that influence eating and body weight in children which may be important in understanding methods to prevent obesity in youth.

DESCRIPTION (provided by applicant): Food is a powerful reinforcer and the reinforcing value of food may be a determinant of food intake. There are individual differences in food reinforcement, as obese find food more reinforcing and consume more food than non-obese. The reinforcing value of food is mediated in part by the dopaminergic system, and research suggests obesity is related to the density of dopamine D2 receptors. In previous research we found smokers with high food reinforcement who had the A1 allele of the dopamine D2 receptor had increased intake of snack foods in an ad libitum eating task. This polymorphism may influence dopaminergic activity by reducing the density of dopamine D2 receptors (DRD2). We have shown a similar pattern of energy intake in pilot research with non-smokers. In addition, these pilot data have shown differences in BMI in relationship to dopamine genotypes and that obesity and dopamine genotypes interact to influence food reinforcement. This application builds upon this research to examine relationships between food reinforcement, obesity, DRD2 genotypes. Three hundred sixteen participants of mixed ethnicity and race, including an equal number of obese and non-obese males and females will be studied. Participants will be genotyped for polymorphisms of the DRD2 genotype, ad lib eating and food reinforcement measured in separate laboratory sessions, and their usual energy intake assessed by repeated 24-hour food recalls. This application provides the opportunity to determine whether 1) the A1 allele of the DRD2 genotype is associated with greater BMI and more obesity;2) food reinforcement and presence of the A1 allele of the DRD2 genotype interact to predict BMI and obesity;3) obesity is associated with increases in food reinforcement;4) obesity and the A1 allele of the DRD2 genotype interact to influence food reinforcement;and 5) ad libitum food consumption and food reinforcement in the laboratory and are related to usual energy intake. This study provides important new information on a behavioral factors that may be related to excess energy consumption, and tests how food reinforcement and the DRD2 genotype may interact in obesity. The findings are relevant to a greater understanding of behavioral and genetic factors related to obesity, as well as providing ideas that may be relevant for treatment interventions for those high in food reinforcement.

DESCRIPTION (provided by applicant): In a series of studies we have shown that children and adults habituate, or show a gradual reduction in responding, to repeated presentations of olfactory, gustatory, or the combination of olfactory and gustatory food cues. The rate of habituation is inversely related to energy intake in a meal, and obese children and adults habituate slower than leaner peers and consume more food. Habituation is a basic form of learning that is observed in many response systems. We believe that habituation is an important process that mediates food regulation during a meal and across meals. However, there has been no research in children that translates basic research on habituation to food into clinical interventions. This center grant is a systematic attempt to translate basic research from our laboratory on habituation to food into effective clinical interventions for overweight children. In the first phase (Years 01-02) we will implement a series of laboratory studies to assess the effects of stimulus specificity and variety, and the simultaneous reduction of variety for high energy density foods while increasing the variety of low energy density foods on short (within meal) and long-term (across meal) habituation. The second phase (Years 02-03) is designed to implement a series of field studies that will extend basic research from the first phase as well as define the optimal interval for reducing variety to facilitate long-term habituation to high energy density foods in the natural environment. The third phase (Years 04-05) is designed to develop and pilot test a family-based behavioral intervention for children that incorporates findings from Phase 2 into a clinical intervention. RELEVANCE Habituation is a theoretically rich behavioral science area that is important to satiation and energy intake regulation. The proposed research will translate research on habituation to clinical interventions for overweight youth in a hierarchical structure, progressing from laboratory studies to controlled field studies to the development of clinical interventions. The translation of this basic science may have important implications for the treatment of pediatric obesity. (End of Abstract)

DESCRIPTION (provided by applicant): We recently found taxing less healthy (high calorie for nutrient) foods reduced energy intake and dietary fat purchased, and increased protein purchased, while subsidizing healthier foods (low calorie for nutrient) increased energy purchased with no change in distribution of macronutrients purchased. The goal of this application is to study whether income, body mass index (BMI), relative reinforcing value of food (RRV) and impulsivity moderate the effects of prices on energy and macronutrients purchased and diet quality in a large sample of 225 ethnically and economically diverse adults. Participants will complete five shopping sessions that vary whether selected snack foods are taxed by +12.5 and +25%, or fruits and vegetables and non- sweetened water are subsidized by -12.5% and -25% in comparison to shopping at reference prices. Specific Aim 1 will evaluate the effect of price changes on energy and macronutrients purchased, with the prediction that taxes will reduce energy and dietary fat purchased and improve diet quality, while subsidies will increase fruits and vegetables and energy purchased. Specific Aim 2 will assess income as a moderator of food purchases, with the prediction that lower income families will be more sensitive to taxes, and show greater reduction in energy and fat purchased and greater improvement in diet quality when these foods are taxed than higher income families. We predict that lower income families will be more responsive to subsidies for healthier foods. Specific Aim 3 will assess BMI as a moderator of food purchases, with the prediction that higher BMI participants will be less sensitive to taxes, and show less reduction in energy and fat purchased and greater improvement in diet quality when these foods are taxed than lower BMI participants. Lower BMI participants will be more responsive to subsidies in purchasing more fruits and vegetables. Specific Aim 4 will test RRV as a moderator of food purchases with the prediction that participants with greater RRV for less healthy items will be less responsive to effects of taxes on reducing energy and fat purchasing and improving diet quality, and conversely, those who have greater RRV for healthier foods will show a reduction in energy and fat purchased and improvement in diet quality as subsidies for fruits and vegetables and non-sweetened water are increased. Specific Aim 5 will assess impulsivity as a moderator of food purchases with the prediction that more impulsive participants will be less responsive to effects of taxes on reducing energy and fat purchasing and improving diet quality, and participants who find food reinforcing and are impulsive will show the smallest reductions in purchases of energy and fat and improvements in diet quality when snack foods are taxed. Conversely, those who are less impulsive will be more likely to show an increase in purchases of fruits and vegetables or non-sweetened water when the prices of fruits and vegetables and non-sweetened water are subsidized. PUBLIC HEALTH RELEVANCE: Project Narrative The proposed research will assess whether income, body mass index, the reinforcing value of food and behavioral impulsivity, moderate the influence of changing prices on energy intake, macronutrients purchased and diet quality. Examining the effects of individual difference factors that influence the effectiveness of price interventions to influence food purchasing will provide insight into public policy decisions that can use taxes or subsidies to influence population health.

DESCRIPTION (provided by applicant): Obesity develops due to positive energy balance, when energy intake exceeds energy expenditure. One factor that may influence energy intake is individual differences in the rate of habituation to food. The rates of salivary habituation or habituation of behavioral responding for food predict energy intake, with slower habituation related to greater energy intake. We have shown overweight or obese youth and adults habituate slower to repeated food cues than leaner youth and adults, but it is not known whether this is a result of being overweight, or whether slower habituation is a risk factor for zBMI gain. This can only be tested using prospective designs in which children who differ in their rate of habituation are studied prospectively to evaluate risk factors for zBMI increases. The goal of this application is to study individual differences in habituation of behavioral responding for food and salivary habituation as risk factors for zBMI and body fat changes over a three year period in 200 8 to 10 year-old non-overweight children. Mixed effects regression models will be used to study whether aggregate measures of baseline salivary habituation and/or habituation of behavioral responding for food (Specific Aim 1) or habituation to foods that differ on basic taste characteristics (sweet, savory, salty, Specific Aim 1a) are independent predictors of trajectories of zBMI and body fat, to assess the relationship between habituation of behavioral responding for food or salivary habituation and energy intake (Specific Aim 2), to assess developmental trajectories in habituation over time (Specific Aim 3), to test the relationship between reflexive, physiological (salivation) and behavioral (responding for food) measures of habituation (Specific Aim 4), and assess whether relative reinforcing value of food and eating in the absence of hunger are risk factors for child zBMI gain (Specific Aim 5).

DESCRIPTION (provided by applicant): Manipulating food prices is one of the most powerful ways to modify food purchasing. An alternative approach is by point of purchase nutrition information using nutrient profiling. The goal of this grant is to assess the independent and combined effects of 1) 25% taxes and subsidies on the least and most nutritious foods based on their nutrient profiles and 2) point of purchase nutrient profiling on nutrient density, energy, energy density and specific nutrients of foods purchased. The study will be undertaken in a sample of ethnically and income diverse adults who do the food shopping for their families. A 2 x 2 factorial design will be used to randomize 800 shoppers to 1) a control arm with usual nutrition information, 2) nutrient profiling information only on all foods in the grocery store, 3) taxes on the 20% lowest nutritional value foods plus subsidies on the 20% highest nutritional value foods only, and 4) nutrient profiling plus the differential taxes and subsidies. Nutrient profiling will be based on NuVal, a comprehensive nutrient profiling system that scores foods on a 1-100 scale based on an algorithm that takes in to account positive (fiber, vitamins, minerals, Omega 3 fatty acids, etc.) and negative aspects of food (trans fat, salt, sugar, etc,) as well as factors such as protein and fat quality, energy density, and glycemic load. NuVal scores predict health outcomes, including all-cause mortality, in a cohort study of 100,000 people, with higher scores (better nutritional value) associated with lower risk for a variety of diseases. Specific Ai 1 will assess the main and interactive effects of point of purchase nutrient profiling and price changes on average nutrient density/100 kcal of all foods purchased, and Specific Aim 1a will assess the main and interactive effects of nutrient profiling and/or price changes on total energy and energy density of foods purchased, average NuVal scores and average values of specific nutrients including fiber, added sugar, saturated fat and sodium, and the main and interactive effects on average NuVal scores and macronutrient composition of purchased foods. Specific Aim 2 will assess the main and interactive effects of nutrient profiling and/or price changes on cost to improve nutrient density/100 kcal. Specific Aim 3 will assess the whether income, body mass index or dietary restraint moderate the effect of nutrient profiling and price changes on nutrient density/100 kcal.

DESCRIPTION (provided by applicant): The prevalence of overweight/obesity in youth has increased 3-fold, so it is important to understand the mechanisms of why so many adolescents are becoming overweight. Normal weight youth may either better regulate energy intake and expenditure in the face of obesigenic experiences or experience fewer obesigenic pressures from social (parent and peer) influences. The discordant sibling methodology controls for an average of 50 percent of genetic variability and is an ideal design for determining whether normal weight and overweight/obese siblings experience non-shared behavioral responsivity and/or exposures to obesigenic environments. If a putative non-shared experience is associated with discordance in obesity then variability in the experience within siblings will be large relative to between families. This research studies the energy balance behaviors (usual eating, physical activity, sedentary) of discordant siblings and key putative non-shared experiences contributing to sibling differences in weight behaviors and thus their discordance in adiposity. Non-shared eating behaviors are likely primary risk factors for the discordance in sibling adiposity. Thus, one set of risk factors to be studied is differential sibling responsiveness to eating paradigms that test increased sensitivity to external eating cues and reduced sensitivity to internal satiety cues. Non-shared experiences affecting energy balance behaviors occur within the context of social influences. Thus, the second set of risk factors to be tested is social influences on eating and activity that occur within (parent influences on eating and activity, via questionnaires) and outside (peer influences on eating via dietary recalls and on physical activity via ecological momentary analysis) the family. 48 same- sex biologic adolescent sibling pairs (24 pairs of boys and girls, age 13 to 17 years) will be studied with an equal number of pairs (n=12) within each sex consisting of a younger-normal weight (BMI <70th percentile) and an older-overweight/obese (BMI > 85th percentile) adolescent, or of a younger-overweight/obese and an older- normal weight adolescent. Given the unique developmental stage of adolescence, their exposure to obesigenic experiences and responsivity to those experiences are likely different than for children or adults, but there are few experimental studies of the mechanisms of obesity in adolescents. The specific aims are to use intraclass correlations to determine adolescent discordant sibling resemblances for energy balance behaviors (Aims: 1a. usual eating, 1b. physical activity, 1c. sedentary behaviors), non-shared eating experiences (Aims: 2a. increased eating cue responsivity, 2b. reduced internal satiety cue sensitivity), and non-shared social influences on eating and activity within (Aim 3a. parent influences) and outside (Aim 3b. peer influences) of the family. This research will provide important information on the mechanisms of adolescent obesity and why youth are becoming overweight in our obesigenic environment.

? DESCRIPTION (provided by applicant): The prevention of Type 2 diabetes in an obese person with pre-diabetes requires developing a healthier lifestyle. The rational approach for someone with pre-diabetes would be to eat healthier, be more active, lose weight, and manage their comorbidities. However, preliminary research suggests that individuals with Type 2 diabetes discount the future and engage in behaviors that maximize current pleasure and short-term gain; thus, daily choices needed to improve future health are rare in this population. Delay discounting (DD) describes the choice of smaller immediate versus larger delayed rewards. This behavioral process is related to a wide variety of health choices, ranging from preventive health to behavioral and medical regimen adherence, including regimens used for Type 2 diabetes. We believe that DD provides a target for one type of self- regulation that can improve a wide variety of health behaviors and medical adherence. Research from our laboratories has shown that episodic future thinking (EFT), a form of prospection which reduces the bias towards immediate gratification, activates brain regions involved in planning and prospection such that future rewards have increased value and the extent of delay discounting is reduced. Cueing individuals to think about future events during inter-temporal decision-making reduces the rate of DD, eating in and outside of the laboratory, and smoking behavior. The overarching goal of this grant is to use an experimental medicine approach to translate basic research on DD and EFT into clinical interventions to prevent the transition from pre-diabetes to a diagnosis of Type 2 diabetes. We are using the grant mechanism RFA-RM-14-020, Science of Behavior Change: Assay Development and Validation for Self-Regulation Targets (UH2/UH3) as this provides for the opportunity to integrate observational, laboratory and field studies to assess relationships between DD and disease self-management, understand mechanisms of these relationships across multiple levels of analysis, and refine interventions in preparation for a clinical trial. e propose a series of observational, laboratory and field studies to identify DD as a behavioral target to improve behavioral and medical adherence and metabolic control in adults with pre-diabetes who are at high risk for development of Type 2 diabetes. Specific Aim 1 will examine the cross sectional relationship between DD, executive function, and fMRI-measured brain activation to predict adherence and metabolic control in persons diagnosed with pre-diabetes. Specific Aim 2 will assess the effects of EFT on DD, fMRI measured brain activation and energy intake in participants with pre-diabetes in the laboratory. Specific Aim 3 will assess the effects f EFT on DD and fMRI measured brain activation under simulations of poverty that increase discounting of the future. Specific Aim 4 extends the study of the effects of EFT on DD, executive function, health behavior change, medication adherence for comorbid conditions and glycemic control after a 6-month target engagement with EFT versus control in a field study for the UH3 component of this application.

? DESCRIPTION (provided by applicant): The inability to delay gratification is cross-sectionally and prospectively related to obesity, and the desire for immediate gratification is fundamental to the inability to delay gratification. People tend to devalue larger future rewards relative to smaller immediate rewards, with greater discounting of the future as the temporal distance between the immediate and delayed rewards increases. This pattern of temporal discounting is known as delay discounting (DD). A novel approach to reducing the bias towards immediate gratification is episodic future thinking (EFT), which can change the context of decision making by engaging the episodic memory to prospectively experience or simulate future events. Cueing individuals to think about future events during inter- temporal decision-making reduces DD. The overarching goal of this grant is to translate basic research on EFT into clinical interventions to treat pediatric obesity. We originally submitted this under grant mechanism PA-11- 063, Translating Basic Behavioral and Social Science Discoveries into Interventions to Improve Health-Related Behaviors as this provides for the opportunity to integrate basic and field studies to refine interventions that can be tested in a pilot clinical trial. We have demonstrated that EFT is associated with a reduction in DD in three samples of adults and one sample of children, that EFT has similar effects on DD in overweight/obese and non-overweight participants, and that EFT is associated with a reduction in energy intake in an ad lib eating task in adults and children. We have shown EFT effects in relation to a present thinking control task, as well as non-future and recent or past thinking control tasks. There has been no clinical research using EFT to modify DD in the treatment of obesity, but since EFT has been shown to decrease DD and energy intake in adults and children, it may be especially suited for a family-based treatment (FBT) of pediatric obesity. To translate EFT to a clinical intervention for pediatric obesity, we propose a series of laboratory, field and clinical studies for overweight/obese 8-12 year-old children and their parents. Specific Aims 1a-1b will assess the specificity of imagery, and process versus goal imagery on DD, energy intake and multiple measures of decision making. Specific Aim 2 is designed to determine the best dose of EFT (4, 8 or 12 weeks of training) to influence DD and energy intake, using the optimal EFT approach based on results of studies addressing Specific Aims 1a-b. Specific Aim 3 will use the optimal treatment package based on previous studies to assess the effects of adding EFT to evidence-based behavioral obesity treatment to evaluate the added benefits of EFT training. Developing effective ways to reduce discounting the future and improve delay of gratification may have important benefits in the treatment of pediatric obesity.

DESCRIPTION (provided by applicant): Family-based treatment (FBT) is a behavioral weight control intervention that targets children who are overweight/obese and their parents, and has the capacity to improve the weight status of non-targeted family members such as siblings. FBT has significant positive effects on body weight in children for up to 10-years of follow-up, and a robust relationship is observed between child and parent outcomes. FBT's concurrent care of two generations of obesity in the family is more efficacious and cost-effective than if family members are treated by their separate health care providers. Despite its recognized efficacy, FBT is mainly available in specialty clinics and many children fail to receive this guideline-based level of treatment, as recommended by the U.S. Preventive Services Task Force. Primary care offers an optimal setting for delivery of FBT by capitalizing on the established relationship between primary care providers and families. Using interventionists co-located within the primary care setting overcomes barriers posed by fragmentation of care, and lack of provider time and training. One of the challenges to integrating childhood obesity treatment into primary care is optimizing limited health care resources. In behavioral weight loss programs, some individuals learn diet, physical activity, and behavior change information quickly, while others learn more slowly. Individuals also differ in their ability to implement treatment recommendations due to individual differences, such as problems with delaying gratification. FBT accommodates these individual differences by using a personalized system of instruction, or a mastery model, in which the content and dose of treatment is calibrated to the needs of the family, ensuring that treatment effort is consistent with need. This multi-site, clinical trial aims to evaluate over a to year period the effectiveness of FBT delivered by a trained interventionist co-located within primary care plus enhanced usual care delivered by the primary care provider (FBT+EUC) compared to enhanced usual care alone (EUC). Participants will be a representative sample of 528 families with a 6-12 year-old child and a parent who are both overweight/obese. Weight changes in approximately 228 siblings who are overweight/obese and between 2-18 years of age will also be studied. This study will test between group differences in child (Primary Specific Aim 1A) and parent (Primary Specific Aim 1B) weight change, as well as weight change in siblings who are overweight/obese (Secondary Aim 1), changes in parent and child delay of gratification, and how changes in delay of gratification are related to parent and child weight changes (Secondary Aim 2), participant level predictors of treatment success (Secondary Aim 3), and how provider attitudes toward evidence-based treatment and perceptions of FBT may relate to their intention to use co- located FBT in their practices in the future (Exploratory Aim 1). Establishing that FBT can be effectively implemented within real world settings is crucial to creating a system by which children and their families who suffer from obesity can be treated in a centralized primary care setting.

ABSTRACT Obesity is a disorder of positive energy balance in which energy intake exceeds energy expenditure. The motivation to eat is a basic human need, which is present at birth. One factor that may lead to increased energy intake is the imbalance between the motivation to eat and the motivation to engage in other behaviors. The motivation to eat versus engaging in other behaviors can be operationalized as the relative reinforcing value of eating versus alternative behaviors. A strong motivation to eat instead of engaging in alternative behaviors has been related to increased energy intake in adults. The motivation to eat is cross-sectionally and prospectively related to obesity in children, adolescents, and adults, and cross-sectionally related to weight status in infants. Shifting the balance from high motivation to eat to increased motivation to engage in alternative behaviors can reduce energy intake, and may be protective against weight gain. We have recently shown that a structured program to enhance music engagement in infants who are strongly motivated to eat can shift their choice from food to music. The goal of this study is to expand on this preliminary research and examine long-term effects of this intervention in infants who are highly motivated to eat. We are proposing to randomize 92 healthy infants who are high in food reinforcement to a music enhancement program versus an attention placebo play date and assess changes in food/non-food reinforcement, infant energy intake, weight for length z-score, and enriched home environment, and follow the development of these infants over a 24 month period. We predict that the music program, in comparison to the control play date, will result in a shift in choice from a motivation to eat to a motivation to engage in alternatives to eating (Specific Aim 1) and thus reduce energy intake (Specific Aim 1a), lower weight for length z-score (zWFL) (Specific Aim 2), and create a more enriched home environment (Specific Aim 3) at each measurement interval. We propose that enhancing the motivation to engage in alternatives to eating represents a novel approach to obesity prevention, and these interventions are easily implemented and scalable.

ABSTRACT The reinforcing value of food, or how hard someone will work to gain access to a specific food,1 is one potential mechanism for weight gain and obesity in children and adults. The reinforcing value of food is cross-sectionally related to obesity in infants,2 children3 and adults,4 and prospectively related to weight gain in children,5 adolescents6 and adults.7 While food reinforcement predicts weight gain, not everyone high in food reinforcement gains weight. One potential protective factor against weight gain is a strong reinforcing value for alternatives to food.4 Lean children find alternatives to food more reinforcing than food, while obese children find food more reinforcing than alternatives.3 Environments in which children grow up differ in terms of access to a variety of alternative reinforcers, such as reading8 and musical instruments.9 The lack of access to alternatives to food reinforcers may be a particular concern for children who grow up in families with low socioeconomic status (SES), who are at increased risk for becoming obese.10-12 We have shown in adults that the relative reinforcing value of food mediates the relationship between educational level or income level and BMI in adults.13 The overall goal of this grant is to study individual differences in food and alternatives to food reinforcement in the home environment as risk and protective factors for child weight gain. We will study 230 6- 9 year-old children who vary in food reinforcement, parental education and alternatives to food reinforcement, and carefully assess the home environment and leisure time activities. Specific aims are to test the hypotheses that the independent effects of food reinforcement and alternative reinforcers, and the relative balance of food reinforcement to alternative reinforcers, predicts weight gain (Specific Aim 1), that a home environment with opportunities for participation in, enjoyment of and access to a variety of leisure and physical activities is related to high reinforcing value of alternatives to food (Specific Aim 2), that a home environment with greater availability of unhealthy foods is related to high reinforcing value of food (Specific Aim 3), that the relative reinforcing value of food mediates the relationship between low parental education and increased risk of obesity in children (Specific Aim 4), and that parental relative reinforcing value of food predicts child relative reinforcing value of food (Specific Aim 5).