Jennifer E. Wildes, Ph.D. - US grants

DESCRIPTION (provided by applicant): Considerable research suggests that major depression (MD) is common in women with bulimia nervosa (BN). Yet, despite more than two decades of research, the precise relationship between these forms of psychopathology remains unknown. This project aims to examine the depressive symptoms and cognitive correlates of MD, BN, and comorbid MD and BN. It is hypothesized that the depression experienced by individuals with comorbid MD and BN will differ from that experienced by individuals with "pure" MD and that evidence for a depressive subtype of BN (i.e., depressive bulimia) will be illuminated. Approximately 100 women meeting one of four diagnostic criteria (MD, BN, comorbid MD and BN, and asymptomatic control) will be recruited for the study. Proposed methods include diagnostic interviews, self-report questionnaires, and information processing tasks designed to assess: (1) depressive and bulimic symptoms, (2) depressogenic cognitive biases, (3) dysfunctional attitudes regarding needs for achievement and approval, and (4) dysfunctional attitudes and cognitive biases regarding weight, shape, and food. The results of this project are expected to illuminate important symptomatic and cognitive distinctions between MD and depressive bulimia. Such findings will have significant implications for the classification of MD and BN and will inform treatment protocols for both forms of psychopathology.

[unreadable] DESCRIPTION (provided by applicant): This Mentored Research Scientist Development Award application describes training and research plans designed to qualify the candidate for a career as an independent mental health researcher with expertise in the implications of co-morbid psychopathology for the etiology, classification and treatment of eating disorders. Unrecognized systematic heterogeneity within the population of individuals with eating disorders may produce inconsistent findings across studies (e.g., if heterogeneous subgroups are entered in different proportions in different studies) and obscure clinically relevant information about etiology, prognosis and treatment response. In this application, the research plan focuses on understanding how heterogeneity in patterns of co-morbid mood and anxiety psychopathology is related to treatment response in patients with anorexia nervosa (AN). To this end, the underlying structure of mood and anxiety disorder co-morbidity will be examined in 150 AN patients using dimensional measures of psychiatric symptomatology and temperament. Participants will be assessed 1-2 weeks after admission for acute (i.e., inpatient or day hospital) treatment at a large, well established specialty care program and then followed closely for 12 months after discharge to determine whether co-morbidity subtypes have utility for identifying predictors of treatment response in AN. Guided by an interdisciplinary team of mentors, advanced training in 1) clinical and etiologic factors relevant to research with AN patients; 2) dimensional approaches to the study of psychopathology; and 3) data analytic techniques for identifying clinical subgroups and modeling longitudinal outcomes will facilitate the candidate's goal of establishing an independent research career focusing on the psychopathology and treatment of AN. Information about differences among AN patients with respect to mood and anxiety disorder symptoms and personality traits will promote treatment development initiatives by identifying potential targets for novel interventions. Further, a better understanding of factors related to negative outcome during the period immediately following discharge from acute treatment may lead to the development of more effective treatments and relapse prevention programs. Finally, understanding robust differences in symptom patterns among patients with AN may provide clues that will promote research on the complex causes of this pernicious disorder. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Anorexia nervosa (AN) in adults is a serious and often refractory psychiatric illness, yet little is known about underlying mechanisms that might serve as targets for the development of novel interventions. One challenge in advancing research on the pathophysiology of AN relates to the substantial within-group heterogeneity that characterizes the illness. For example, the Diagnostic and Statistical Manual of Mental Disorders includes two subtypes of AN - restricting (AN-R) and binge-eating/purging (AN-BP) that differ with respect to the presence of binge eating or purging (i.e., self-induced vomiting or the misuse of laxative, diuretics or enemas) episodes. Although there is some evidence that AN-R and AN-BP are distinct, the mechanisms that separate these groups remain elusive. Moreover, similarities and distinctions between AN-BP and bulimia nervosa (BN) underscore the need to identify processes that are shared by and unique to AN-R, AN-BP and BN. Accordingly, the overall goal of this study is to test a conceptual model linking heterogeneity in symptom presentation across the AN-BN spectrum to variations in the salience of two facets of cognitive inflexibility - attentional set-shifting (i.e., the ability to shift attention between two abstract stimulus dimensions) and reversal learning (i.e., the ability to alter behavior in response to changes in reinforcement contingencies). Importantly, attentional set-shifting and reversal learning are neurobiologically distinct, with correlates in the ventrolateral prefrontal cortex/anterior cingulate cortex and orbitofrontal cortex/ventral striatum, respectively. Cognitive inflexibility has received much attention as a putative biomarker of AN, but previous studies have relied primarily on multidimensional clinical neuropsychological measures that do not map on well to underlying neural mechanisms, and findings have been mixed. This study is guided by the hypothesis that heterogeneity in AN can be elucidated by identifying distinct aspects of altered function in fronto-cingulate circuitry mediating attentional set-shifting and fronto-striatl circuitry mediating reversal learning. Thus, this study will use both behavioral tasks outside of the scanner (i.e., Intradimensional/Extradimensional shift task from the Cambridge Neuropsychological Test Automated Battery and a probabilistic reversal learning task) and functional magnetic resonance imaging with conceptually-relevant neurocognitive probes to assess and separate behavioral and neural facets of attentional set-shifting and reversal learning across the AN-BN spectrum. Four groups of participants aged 18-55 years will be recruited: 1) AN-R with no history of binge eating or purging (n = 30); 2) AN-BP (n = 30); 3) BN with no history of AN (n = 30); and 4) psychiatrically healthy controls (n = 30). This study is innovative and significant as the first effort to examine the separate contributions of attentional set-shifting and reversal learning to phenotypic heterogeneity across the AN-BN spectrum. Findings will have important implications for neurobiological models of eating disorders and the development of novel interventions designed to target subgroup-specific pathophysiological processes.