Nicole Karcher
Assistant Professor
Department of Psychiatry
Washington University School of Medicine
Psychotic-like experiences (PLEs), including unusual thoughts and perceptual experiences, represent transdiagnostic markers of later diagnosable mental health concerns. Dr. Karcher’s research program focuses on identifying the genetic, cognitive, neural, and environmental mechanisms underlying PLEs, with the goal of clarifying pathways of vulnerability and resilience. Leveraging large-scale longitudinal datasets, including the Adolescent Brain Cognitive Development (ABCD) Study, this research applies advanced analytic approaches, such as machine learning and structural equation modeling, to characterize patterns of symptoms and risk factors over time. Findings to date demonstrate that PLEs are associated with widespread impairments across domains, including elevated polygenic liability for schizophrenia, cognitive deficits, and structural and functional neural alterations. Additionally, PLEs are strongly linked to environmental exposures, such as trauma life events, underscoring the multifactorial etiology of these experiences. Importantly, this research highlights that PLEs that are both persistent and distressing are associated with greater impairments across risk domains, pointing to a subset of youth at heightened risk for adverse outcomes. Taken together, this research advances understanding of the developmental origins of psychosis spectrum symptoms and provides a foundation for identifying targets for early detection and intervention efforts in youth.
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