Brain-Behavior Mechanisms of Social Cognition in First-Episode Psychosis

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PROJECT SUMMARY Psychotic disorders are serious illnesses that lead to significant functional impairment, even during the early course of illness (i.e., first-episode psychosis; FEP). Social cognition is a strong predictor of key functional outcomes in psychosis (i.e., social and occupational functioning) and among social cognitive domains, mentalizing – the ability to infer and reason about the mental states of other people – is most robustly impaired and simultaneously most predictive of outcomes. However, existing interventions addressing social cognitive dysfunction in psychosis are minimally effective in improving real-world outcomes. Further, though psychosis studies have revealed abnormal function in brain areas comprising the mentalizing network (MN; e.g., medial prefrontal cortex and temporoparietal junction), the vast majority of existing studies have utilized fMRI paradigms that use non-human or non-interactive stimuli that may limit ecological validity and further fail to examine associations between neural function and real-world outcomes. Collectively, social cognition is a critical factor in psychosis that remains poorly understood. Thus, the proposed study will combine neural, behavioral, and real- world functioning measures to delineate brain-behavior mechanisms of social cognition in FEP. The study will enroll 45 FEP individuals and 45 matched non-clinical controls (NCC) and assess their neural (i.e., fMRI) and behavioral (i.e., validated laboratory-based measures) social cognitive function as well as their real-world social and occupational behavior. Data from this study will allow for an innovative investigation of whether MN dysfunction is associated with social cognitive performance on validated behavioral tasks both across and within FEP and NCC participants (Aim 1), and how these brain-behavior measures of social cognitive performance relate to laboratory-based measures of social and occupational functioning (Aim 2). The current study will also examine the extent to which MN function predicts real-world social and occupational functioning assessed via ecological momentary assessment (Aim 3). This proposal concurrently provides an excellent opportunity to receive mentor-directed, hands-on training in several key areas necessary to refine the candidate’s knowledge and skill-sets. Though the candidate has extensive clinical research experience in FEP and has completed foundational fMRI training, she proposes a training plan focused on three new domains: 1) advanced social- cognitive neuroscience and fMRI task development, 2), linking of fMRI to behavioral constructs of social cognition and functional outcome, and 3) translation of fMRI and behavioral constructs to psychosis. The proposed study coupled with completion of the training plan will effectively launch the candidate toward her long-term goal of an independent career in the translational neuroscience of social-cognitive dysfunction in early psychosis, and will lay the foundation for future, high-impact R01 studies focused on refined identification and targeting of biobehavioral factors influencing social and functional outcomes.