Pamela Keel - US grants

The purpose of this study is to determine if amount of food consumed is clinically meaningful in defining binge-eating episodes within bulimia nervosa.-purging subtype (objective bulimia nervosa-OBN) and women who would meet DSM-IV criteria for bulimia nervosa-purging subtype except that their perceived binge episodes do not involve an objectively large amount of food (subjective bulimia nervosa-SBN). Based on previous research and a pilot study, it is hypothesized that women with OBN and SNB will not differ in levels of Axis I psychopathology or eating pathology. However, women with OBN are predicted to have significantly higher levels of impulsiveness and Axis II, Cluster B Personality disorders compared to women with SBN. Structural clinical interviews and questionnaire assessments will be completed with 40 subjects with OBN and 40 subjects with SBN in order to test the proposed hypotheses. Subjects will be reassessed at 6-month follow-up to determine the predictive validity of distinctions between OBN and SBN in women. Understanding whether size matters in defining binge-eating episodes within bulimia nervosa is crucial in refining the definition and clarifying risk factors of bulimia nervosa.

The long term objectives of this study are to explore the utility of defining binge-eating episodes in bulimia nervosa by the amount of food consumed and to reveal factors that contribute to the development or maintenance of bulimic symptoms. An additional objective is to improve the recognition of an alternative symptom cluster that resembles bulimia nervosa-purging subtype, except that perceived binge episodes do not involve objectively large amounts of food. Recent research indicates that a substantial number of young women suffer from this alternative symptom cluster (subjective bulimia nervosa-SBN) suggesting that SBN represents a significant public health concern. One specific aim of this study is to test the hypothesis that, like women with DSM-IV bulimia nervosa, women with SBN demonstrate clinically significant levels of distress and impairment. A second aim is to demonstrate that SBN is distinct from DSM-IV bulimia nervosa and thus should not be combined with this syndrome within one diagnostic category. The study proposes to extend preliminary data suggesting that women with bulimia nervosa have higher levels of impulsiveness compared to women with SBN. In addition, this study proposes a novel examination of whether, compared to women with SBN, women with bulimia nervosa demonstrate lower levels of satiety and blunted cholecystokin (CCK) release following a rest meal. The study will include 30 women with DSM-IV bulimia nervosa-purging subtype, 30 women with SBNm and 30 non-eating disordered control females. Subjects will complete psychological assessments including structured clinical interviews and standardized questionnaire assessments of depression, anxiety, impulsiveness, and social and occupational functioning. Subjects will also participate in assessments of post-prandial satiety and CCK release. This study will test a model of bulimia nervosa in which deficient satiety signals fail to decrease the impulse to eat which, combined with poor impulse control, increases the liability to experience objectively large binge-eating episodes by the amount of food consumed and reveal etiologic or maintaining factors for objectively large bing episodes in bulimia nervosa. Further, this study has the potential to identify a new subtype of eating disorder that is worthy of study, treatment, and inclusion in nosological schemes.

DESCRIPTION (provided by applicant): Very little is known concerning the secular and longitudinal trends associated with bulimic syndromes. This study offers a unique opportunity to 1) examine rates of bulimia nervosa (BN) and eating disorders not otherwise specified (EDNOS) across 1982, 1992, and 2002 in college students, 2) examine and compare the longitudinal courses of BN and EDNOS at 10- and 20-year follow-up, and 3) evaluate secular trends, longitudinal course, and prognostic utility of eating disorder-related variables such as weight, body image disturbance, dieting, and disordered eating behaviors. Thus, this investigation could provide much needed data for a significant source of psychiatric morbidity among young adult women. In the springs of 1982 and 1992, a total of 2400 Harvard undergraduates (1600 women and 800 men) were randomly sampled to participate in a study of weight, body image disturbance, dieting, disordered eating behaviors, and BN. In 1992, participants in the 1982 study were contacted to participate in a follow-up study. In the spring of 2002, this study proposes to collect data from a new cohort of undergraduates (800 women and 400 men) and to contact participants from the 1992 and 1982 cohorts (1189 women and 511 men) for 10- and 20-year follow-up evaluations, respectively. The investigation will be conducted in two phases: a survey phase and an interview phase. The survey phase will replicate methods employed for data collection in 1982 and 1992 in order to insure comparability of results. Surveys include items about demographic background, height and weight; concerns about dieting, body weight, and shape; 5 scales of the Eating Disorders Inventory (Buhrnia. Drive for Thinness, Maturity Fears, Perfectionism, and Interpersonal Distrust); and BN symptoms. In addition, surveys will include the Eating Disorder Diagnostic Scale for termination of DSM-IV symptoms of anorexia nervosa, BN, and binge eating disorder. On the basis of self-report survey data, all subjects diagnosed with BN or EDNOS and controls matched to these subjects on age, sex, race, ethnicity, and SES will be recruited for participation in the interview phase of the study. Interviews will establish the validity of survey assessments, as well as provide data on psychosocial function, comorbidity, and treatment history for a nonclinical sample of individuals with eating pathology. The long-term goals of this study are to capture the changing epidemiology of bulimic disorders; to evaluate the long-term correlates and consequences of bulimic syndromes that support meaningful distinctions between BN and its subthreshold forms; and to identify contributants to the development, maintenance, and outcome of BN.

binge eating disorder; bulimia nervosa; satiations; cholecystokinin; impulsive behavior; behavioral /social science research tag; clinical research; human subject; female;

The Integrated Clinical Neuroscience (ICN) Training Program, operating in the Psychology Department at Florida State University for the past four years, seeks to train the next generation of investigators to become leaders in translational research who will make major advances across several areas of psychopathology characterized by dysregulated (?disinhibited?) behaviors including eating disorders, suicidality, trauma-related disorders, and aggression. These problems are associated with significant psychological and medical morbidity, elevated mortality, and high economic burden, underscoring the need for research that translates the neural mechanisms that underlie normal and abnormal behavior in animals into clinical studies of the causes and treatment of mental disorders. However, segregation of doctoral training in Clinical Psychology and Neuroscience, with separate course requirements, lab experiences, and exposure to outside speakers, impedes new scientists' preparation to undertake translational approaches in their own research. The ICN Training Program was designed to break down these barriers. Here, we seek continued funding to provide integrated instruction, research experience, and mentorship to 4 predoctoral ICN trainees earning Ph.D.s in Clinical Psychology and Neuroscience through several components: 1) cross-area courses, 2) cross-area lab rotations to conduct collaborative, cross-area research, 3) a Special Speaker Series in which trainees present their ongoing research to national scholars conducting translational science, and these scholars present their work to trainees, ICN training faculty, the Department, and community, 4) presentation of research at conferences and in published papers, and 5) instruction in grant writing. Predoctoral trainees apply for the ICN Training Program by describing research they plan to conduct in collaboration with their primary advisor and cross-area mentor, classes they will complete, and how the ICN Training Program will contribute to their career development as translational scientists. ICN training faculty come from the Clinical and Neuroscience programs based on cross-area connections in research addressing dysregulated behaviors. Trainees are appointed at the beginning of their 2nd through 4th year to ensure selection of the most promising trainees who have completed basic program requirements and have established research interests in their primary advisor's lab that they can extend through work in a cross-area lab rotation. The duration of support is 2 years. Our training model has produced a highly accomplished first cohort of ICN trainees, two of whom are now in prestigious postdoctoral positions. Training faculty continue to excel in securing grant funding and training students for productive research careers with strong publication records. Continuation of the ICN Training Grant for an additional five years will build upon our accomplishments and ensure that a second cohort of Ph.D. students is ideally positioned to initiate cutting-edge translational research as they develop independent programs of research to address mental disorders characterized by dysregulated behaviors.

Bulimic syndromes (BN-S) are characterized by large out-of-control binge episodes, span the three DSM-5 eating disorder categories of anorexia nervosa-binge purge subtype (ANbp), bulimia nervosa (BN), and binge eating disorder (BED), and vary considerably in illness severity and course. Our long-term objectives are to identify biobehavioral predictors of illness trajectory in BN-S so that treatments may be developed to address key factors influencing the severity and course of binge eating. The specific aims of this study are to test a model in which weight suppression (WS) leads to deficient circulating leptin, which contributes to blunted postprandial glucagon-like peptide 1 (GLP-1) response, which causes alterations in the RDoC core constructs of approach motivation and sustained responsiveness to reward, which then contribute to BN-S severity and maintenance. WS (the difference between an individual's highest weight and current weight) has emerged as one key predictor of severity and maintenance of BN-S, and investigators have posited a biobehavioral mechanism for this association. Yet, no study has evaluated how the biological consequences of WS may contribute to alterations in RDoC core constructs proposed to contribute to binge eating. Our model posits that the same set of physiological consequences of WS contribute to binge eating by 1) increasing drive/motivation to consume food (approach motivation), and 2) decreasing ability for food consumption to lead to a state of satiation/satisfaction (sustained responsiveness to reward). Approach motivation will be measured both behaviorally as breakpoint on progressive ratio tasks for food and non-food reinforcers and by self-report. Sustained responsiveness to reward (satiation) will be measured both behaviorally as food intake in an ad lib meal and by self-report. Participants (N=320) with BN-S and non-eating disorder controls, ranging in BMI from 16 to 35 kg/m2, will be assessed for WS, leptin, GLP-1 response to a fixed meal, approach motivation, ability to achieve satiation in an ad lib meal, self-report measures of core constructs, and binge eating at baseline, 6-, and 12-month follow-up, to produce the first study of biobehavioral predictors of illness trajectory in BN-S transdiagnostically. Examining the integration of approach motivation and satiation through the same set of physiological mechanisms represents a major innovation as it translates cutting-edge research in basic science to understand clinical phenomena in BN-S. If differences in illness trajectory across ANbp, BN, and BED are attributable to the underlying dimension of WS, this will fundamentally alter conceptualization of BN-S from three eating disorder categories to one eating disorder. If findings support biobehavioral distinctions across the BMI range, this would provide important information in what treatments would work in whom. Moreover, our focus on factors that are modifiable via behavioral and pharmacological interventions increases the public health significance of this work by facilitating novel treatment approaches to ameliorate distress, disability, and death in syndromes accounting for an important segment of those suffering from eating disorders.

Very little is known about how the prevalence of eating disorders (EDs) has changed across generations or the trajectory of EDs over the course of adult development. This study offers a unique opportunity to 1) examine ED point prevalence and mean scores on dimensional ED measures across 5 cohorts of college students randomly sampled from the same university population in 1982, 1992, 2002, 2012, and 2022, 2) examine the longitudinal course of eating pathology from late adolescence to midlife (18 to 62+ years), and 3) identify predictors of course focusing on factors unique to adulthood. This project will offer new insights into how generation impacts gender differences in EDs and how both gender and generation impact longitudinal trajectory. This project builds on a study initiated in 1982 and replicated with the addition of new cohorts and extended with follow-up of well-characterized, established cohorts every 10 years since its inception. In the spring of 2022, 1600 undergraduates (800 women and 800 men) will be randomly sampled to complete surveys of weight, height, body image disturbance, dieting, disordered eating behaviors, and EDs. In addition, participants who completed these assessments in college will be sought for 10-, 20-, 30-, and 40-year follow- up. We project collecting 20-year follow-up data in over 1,700 adults (>70% retention), including nearly 500 men and over 400 participants from ethnic/racial minority groups. These data will allow us to examine generation X age effects to determine whether course of eating pathology differs across Baby Boomers (1982 cohort), Generation X (1992 cohort), and Millennials (2002 cohort). The investigation will be conducted in two stages: a survey phase and an interview phase. The survey phase will replicate methods employed for data collection in all prior waves to ensure comparability of data. Surveys include detailed items about demographic background; height and weight; dieting, body image, and exercise; 5 scales of the Eating Disorders Inventory (Bulimia, Drive for Thinness, Maturity Fears, Perfectionism, and Interpersonal Distrust); and symptoms of anorexia nervosa, bulimia nervosa, binge-eating disorder, and permit DSM-5 ED diagnosis and diagnoses of their partial and subthreshold variants. In addition, beginning in the 3rd wave, surveys included the Eating Disorder Diagnostic Scale which is included as a core ED assessment for the NIMH. On the basis of self-report survey data, all subjects diagnosed with an ED and controls matched to these subjects on age, sex, race, and ethnicity will be recruited for participation in the interview phase of the study. Interviews will establish the validity of survey assessments, as well as provide data on psychosocial function, suicidality, comorbidity, and treatment history for a nonclinical sample, similar to their use in the 3rd wave, 20 years ago. The long-term objectives of this project are to evaluate whether we are making progress in reducing the public health burden associated with EDs, determine the adult developmental course of EDs, and identify predictors of ED trajectory that can be translated into targets for intervention, including what to modify, in whom, and when.