6.4 Structural and Functional Brain Abnormalities Associated With Distinct Dimensions of Subthreshold Psychosis in Youth

Abstract

Abstract Background: Neuroimaging in population-based studies of youth can help identify neurodevelopmental abnormalities associated with psychosis-spectrum symptoms and risk. To date, little work has examined specific dimensions of psychosis spectrum symptoms in this population, a gap we sought to address here in the large Philadelphia Neurodevelopmental Cohort (PNC). Methods: In the PNC, ~20% of youth were categorized as psychosis spectrum (PS) based on elevations in positive or negative/disorganized symptoms. Baseline multimodal imaging data were acquired from 1601 youth from the PNC, aged 8–23 years, 452 of whom were identified as PS. Dimensional subclinical positive and negative/disorganized were derived from factor analysis of a structured clinical interview; cognition was measured with the Penn Computerized Neurocognitive Battery. Results: Subthreshold positive and negative symptom severity was moderately correlated (r = .37); reduced cognitive performance was modestly associated with both positive (r = −.14) and negative (r = −.17) domains. These 3 domains showed distinctive associations with functional and structural imaging. In the working memory fMRI task, PS showed reduced activation in executive control circuitry, which correlated with cognitive deficits (r = .32) but not positive or negative symptoms. During emotion identification fMRI, PS demonstrated elevated amygdala responses to threatening facial expressions, which correlated selectively with positive symptom severity (r = .16). Structural imaging revealed gray matter volume reductions in hippocampus associated with positive symptom severity (r = −.15). In contrast, unmodulated gray matter density was selectively reduced in the bilateral nucleus accumbens in association with negative symptom severity (r = −.16). Conclusion: These findings extend support for the continuum view of psychosis by demonstrating that specific circuit–symptom correlations found in schizophrenia are also evident in youth with subthreshold symptoms. Complementing the more common categorical focus, dimensional examination of specific illness domains may identify neurodevelopmental abnormalities within key brain circuits. This in turn can help parse clinically-relevant heterogeneity within the at-risk population and facilitate the development of early diagnostic and prognostic tests and novel treatments designed to target-specific symptom domains.