This is an NIMH Exploratory/Developmental Research Grant Program (R21) proposal entitled, ?Characterization of Variability in Motivation and Reward in Psychosis.? Motivational deficits are a hallmark of schizophrenia and related disorders and are associated with poor community outcomes and reduced treatment adherence and efficacy during behavioral interventions such as cognitive remediation. Motivation and reward are not unitary constructs but are comprised of measurable and separable domains, as delineated in the RDoC Positive Valence Systems Domain, which may be differentially associated with illness traits, outcomes, and treatment response. However, characterization of dysfunction across the PVS domain using multiple measures across units of analysis has not been undertaken in psychosis, and whether profiles of deficits emerge and are differentially associated with clinical and community functioning or predictive of treatment outcomes has not yet been tested. In the present proposal we aim to measure multiple constructs across the PVS Domain using a multivariate battery across units of analysis in a cross-diagnostic sample of patients with psychosis (n=200) and healthy controls (n=50), and examine the structure of this domain using principal components analysis. We will use emergent factors to then a) examine associations between factors and clinical, cognitive, and community functioning measures, and with motivated behaviors using validation measures; and b) identify groups of patients who share similar PVS factor profiles using cluster analysis. Similar approaches have successfully uncovered meaningful groupings previously obscured by group-level means comparisons (5, 8) using such techniques, permitting the examination of profiles of patients along constructs of interest map more closely to outcomes and neurobiological correlates than do heterogeneous groupings like diagnosis (6,7). Findings from this project will position us to examine biological mechanisms that underpin these factors (3), and ? critically ? guide treatment efforts toward targeting these specific processes in our ongoing program of research. The PI is an early stage investigator and K23 Awardee with a career focus on characterization of the nature and course of multidimensional symptom domains such as cognition and PVS symptoms across the psychosis spectrum, and treatments such as cognitive remediation to target these deficits.

Public Health Relevance

Motivational deficits in psychosis are core and related to poor community outcomes and poorer response to behavioral interventions such as cognitive remediation. Because there are many aspects of motivation, not all of which show abnormalities in all patients, we aim to carefully characterize this symptom domain, examine associations amongst symptom factors and clinical, cognitive, and community outcomes, and identify different profiles of motivation/reward characteristics in order to group people with shared motivational characteristics. Clarification of this key domain across diagnoses will improve our ability to develop effective interventions to target this central and disabling symptom dimension.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Adult Psychopathology and Disorders of Aging Study Section (APDA)
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Morris, Sarah E
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Mclean Hospital
United States
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Lewandowski, Kathryn E; McCarthy, Julie M; Öngür, Dost et al. (2018) Functional connectivity in distinct cognitive subtypes in psychosis. Schizophr Res :
Lewandowski, Kathryn E (2018) Hastening treatment development in bipolar disorder: Evaluation of consensus-based recommendations for cognition trials. Bipolar Disord 20:70-71
Lewandowski, Kathryn E; Ongur, Dost; Keshavan, Matcheri S (2018) Development of novel behavioral interventions in an experimental therapeutics world: Challenges, and directions for the future. Schizophr Res 192:6-8