Ayelet Meron Ruscio - US grants

The proposed research program aims to begin to test whether anxiety is categorical or dimensional in nature. In years 1 and 2 of the research program, a series of investigations will empirically evaluate the structural nature of three anxiety disorders: generalized anxiety disorder, posttraumatic stress disorder, and social phobia. Each disorder will he examined in large clinical and analogue samples using sophisticated taxometric procedures designed to test latent structures. Follow-up analyses will inspect the overlap between the three disorders to increase understanding of their frequent comorbidity. In years 3 and 4, a therapy outcome investigation will assess the efficacy of a classification scheme (either categorical or dimensional) derived from taxometric analysis of generalized anxiety disorder. The investigation will compare this classification scheme to traditional DSM-IV diagnosis on the relative ability to predict prognosis, treatment response, and functional outcome following a brief clinical intervention for chronic worry. Results of the proposed research are expected to enhance scientific understanding of the nature of anxiety, with important implications for the conceptualization, assessment, investigation, and treatment of the anxiety disorders.

[unreadable] DESCRIPTION (provided by applicant): This revised application for a Mentored Research Scientist Development Award (K01) outlines a 5-year training plan that will prepare the candidate for an independent research career focusing on the study of emotional disorders and their comorbidity. The candidate's career goal is to investigate the latent boundaries that separate the mood and anxiety disorders from one another and from normal emotions and to use this knowledge to enhance the classification and assessment of emotional disturbance. However, while the candidate has a strong background in the anxiety disorders and in Meehl's taxometric method, she requires skills in 4 additional areas to achieve her long-term goals: (1) proficiency in the statistical techniques of classification research beyond the taxometric method; (2) in-depth knowledge of the mood disorders; (3) understanding of variables beyond symptom data (i.e., neurobiological, personality, genetic) that are important for the classification of emotional disorders; and (4) experience with psychiatric epidemiology, the field traditionally enlisted to refine nosological systems. These gaps in knowledge will be addressed by: (1) didactic training in statistics, mood disorders, neurobiology, personality, and genetic epidemiology; (2) clinical training in emotional disorders and their comorbidity; (3) training in psychiatric epidemiology through research apprenticeships on two major surveys designed to inform revisions for ICD-11 and DSM-V; and (4) the conduct of a mentored research project. The research project will integrate the methods of structural and epidemiological research with the aims of (i) delineating the full latent structure of 6 commonly co-occurring mood and anxiety disorders in epidemiological samples, (ii) evaluating the epidemiological consequences of modifying diagnostic criteria and thresholds based on information about latent structure, and (iii) examining epidemiological correlates of pure and comorbid emotional disorders classified using information about their latent structure. This project is expected to inform the development of an R01 proposal to support further research into mood-anxiety comorbidity and to round out the candidate's ability to conduct productive, independent research in this area. The project is also expected to yield results with considerable relevance for public health, with the potential to lead to more valid and useful diagnostic assessments, better detection of individuals in need of services, and more effective prevention and treatment of emotional suffering. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Anxiety and mood disorders co-occur at levels far greater than chance and are considerably more severe, persistent, and disabling in the comorbid than the noncomorbid form. However, although comorbidity is vitally important for efforts to understand, prevent, and treat emotional suffering, it is poorly understood. A promising starting point for explaining comorbidity is the relationship between generalized anxiety disorder (GAD) and major depressive disorder (MDD). Evidence that GAD and MDD share nearly all of their genetic risk hints at the existence of common processes that increase vulnerability for both disorders-processes which may represent potent targets for research and treatment. However, no one has yet attempted to determine just what is inherited by persons at risk for these disorders, nor what accounts for the presence of anxiety or depression in persons vulnerable to both. The central aim of this project is to evaluate 3 biobehavioral mechanisms that are hypothesized to contribute to GAD (threat sensitivity), MDD (reward responsiveness), or their comorbidity (perseverative thought). These candidate mechanisms will be studied in 4 groups-GAD, MDD, comorbid GAD-MDD, and healthy controls-that allow specific predictions to be tested about the relations of mechanisms to disorders. Mechanisms will be assessed on-line as they occur naturally in response to threat and reward experiences in the laboratory (using experimental paradigms) and in daily life (using ecological momentary assessment). Three studies will characterize the mechanisms in the disorder groups, address unresolved questions about the form of their disruption in GAD and MDD, and explore pathways through which they interact with the environment to maintain emotional disturbance. Discoveries resulting from this work are expected to inform interventions that, by targeting common as well as disorder-specific processes with increased precision, have the potential to improve outcomes for comorbid disorders. This would represent a significant step forward in addressing anxiety-mood comorbidity and its associated burden. PUBLIC HEALTH RELEVANCE: The burden of anxiety and depression is not distributed evenly in the population but is concentrated in a subset of individuals who suffer from multiple disorders. The current project seeks to isolate and characterize risk mechanisms that are specific to, and shared by, anxiety and depression. This represents an important step toward improved prediction, prevention, and treatment of comorbid disorders and their associated burden.