Amy Pinkham, PhD - US grants

DESCRIPTION (provided by applicant): The present application is in response to Strategy 3.2 of the NIMH strategic plan, which requests the development of standardized measures of functional outcome that can be utilized in clinical assessment and intervention studies. This goal will be met by achieving a consensus definition of crucial social cognitive domains and developing psychometrically sound measures that can be used to assess these domains in various types of treatment research involving people with schizophrenia. Social cognition is a set of cognitive processes that are involved in how individuals understand and respond to social information. The social cognitive abilities of individuals with schizophrenia have been strongly linked to functional, real-world social outcomes, and social cognition is increasingly seen as a viable treatment target. It is therefore imperative that sensitive and psychometrically sound measures be developed for accurate assessment. The first phase of the proposed project will conduct an extensive survey of experts in the field to identify the core domains of social cognition and current tasks that assess each domain (Specific Aim 1). A carefully selected smaller group of expert panelists will then convene to evaluate each identified domain and task using consensus attainment procedures previously developed by the RAND Corporation and used in previous large-scale mental health assessment studies. The panel will reach a consensus on the most relevant domains of social cognition and select the most promising tasks within each domain for further study and development (Specific Aim 2). These candidate measures will then be compiled into a comprehensive battery and administered to a large sample of individuals with schizophrenia and healthy controls at two different sites (University of Miami and Southern Methodist University). Data will be utilized to assess the reliability and validity characteristics of each task (Specific Aim 3). Data from this psychometric study will be shared with a scientific advisory group to evaluate the results. Otherwise promising candidate measures that show inadequate characteristics will then be modified and pilot tested to ensure the success of the modifications (Specific Aim 4). Finally, a three-site validation study (to increase the generalizability of the findings) will then be conducted to determine the psychometric properties of the final measures (Specific Aim 5). Data from this portion of the project will also be used to systematically examine the relationship between these refined social cognition measures and aspects of functional outcome. The findings of this project will yield a uniform definition of social cognition that will guide future research and develop psychometrically sound measures of social cognition that will be valuable in assessing the effectiveness of psychosocial and biomedical interventions. PUBLIC HEALTH RELEVANCE: Schizophrenia is a complex brain disorder that includes significant impairments in the ability to function in everyday settings that are clearly related to social cognitive deficits. Empirically based and sound instrumentation is key to assessing the outcomes of interventions targeted to ameliorate social cognitive impairments. The goal of the proposed study is to identify and improve the best existing measures of social cognition so that they can be suitably applied in large-scale treatment studies. This project will develop consensus on the critical elements of social cognition, identify the best existing measures of social cognition, collect new data to evaluate the psychometric characteristics of these measures, modify them to optimize their utility, and collect additional data to determine the psychometric properties of the final measures based on a large and diverse sample, while focusing continuously on real-world functional outcomes and the role of social cognition, as compared to neurocognition and social competence, for the prediction of real-world functioning

Project Summary The present application is in response to Strategies 1.3 and 2.2 of the NIMH strategic plan, which respectively call for the identification of brain circuits that contribute to various aspects of mental function and dysfunction and the identification of clinically useful biomarkers and behavioral indicators that predict change across illness trajectories. We propose to contribute to these goals by applying the Research Domain Criteria (RDoC) approach to the symptom of paranoia and attempting to identify a neurobehavioral mechanism for paranoid ideation. Paranoia is a distressing and debilitating psychotic symptom that is both transdiagnositic and dimensional in that it is experienced by individuals across a wide range of psychiatric diagnoses and is commonly experienced by individuals in the general population. The current proposal conceptualizes paranoia as lying at the intersection of two Domains: Social Processes (specifically, Perception and Understanding of Others and Reception of Facial Communication) and Negative Valence Systems (specifically, Sustained Threat). Existing knowledge links each of these constructs to function of the amygdala, and our pilot work demonstrates that paranoia is associated with increased baseline activity of amygdala and related neural circuits. We therefore hypothesize that increased tonic, or baseline, activity of social process and negative valence neural circuits will constitute a neurobehavioral mechanism for paranoia across the continuum from healthy to pathological. To test this hypothesis, data will be collected across three RDoC Units of analysis ? circuits (baseline and stimulus-related neural activity), behavior (judgments of trustworthiness and emotion from facial stimuli), and self-report (paranoia and social functioning rating scales). These data will be used to test longitudinal associations between our proposed mechanism and paranoid ideation (Aim 1), determine if experimentally induced paranoia yields predicted changes in the proposed mechanism (Aim 2), and establish how our proposed neurobehavioral mechanism varies dimensionally across the paranoia continuum (Aim 3). The findings of this project will not only contribute to new classification strategies that utilize neurobiological measures but also to the identification of novel treatment targets and biologically-based predictors of illness trajectory.

Project Summary The present application is in response to Strategy 3.1 of the NIMH strategic plan, which calls for the identification and validation of new targets for treatment development that underlie disease mechanisms. We propose that introspective accuracy (IA) represents a critical novel target for intervention and will therefore meet this goal by comprehensively examining IA in individuals with schizophrenia and individuals with bipolar disorder. Both disorders are characterized by significant social dysfunction, which impairs quality of life and impedes independent living and employment. IA, a term referring to one's ability to evaluate his or her own decisions as correct or incorrect (i.e. to know what one knows and what one does not know), is impaired in individuals with severe mental illness, and our pilot work indicates that impairments in IA are better predictors of functional outcome than are cognitive or functional abilities themselves. This suggests that targeting impaired IA in treatments may lead to improved day-to-day function and quality of life. By assessing IA across the functionally-relevant domains of neurocognition, social cognition, social competence, and functional capacity, we will test the overarching hypotheses that IA is a critical determinant of real-world functioning (Specific Aim 1), that IA is distinct from other forms of self-awareness and uniquely contributes to outcomes (Specific Aim 2), and that within individuals, mood and psychotic symptoms dynamically influence both the degree and direction of introspective deficits (Specific Aim 3). Our study design will allow for the assessment of IA at both inter- and intra-individual levels by utilizing Ecological Momentary Assessment (EMA) to obtain longitudinal data on IA and symptoms. The findings of this project will yield the most thorough understanding of IA to date spanning multiple domains and broadly sampled across two diagnostic constructs. Results will identify a novel treatment target and provide a foundation for the development of psychosocial and neurobiological interventions.