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Longitudinal Trajectories of Cognition and Neural Metrics as Predictors of Persistent Distressing Psychotic-Like Experiences Across Middle Childhood and Early Adolescence

Karcher, N. R.; Dong, F.; Johnson, E. C.; Paul, S. E.; Kilciksiz, C. M.; Oh, H.; Schiffman, J.; Agrawal, A.; Bogdan, R.; Jackson, J. J.; Barch, D.

2025-01-22 neuroscience
10.1101/2025.01.20.633817 bioRxiv
Show abstract

ObjectivesPsychotic-like experiences (PLEs) may arise from genetic and environmental risk leading to worsening cognitive and neural metrics over time, which in turn lead to worsening PLEs. Persistence and distress are factors that distinguish more clinically significant PLEs. Analyses used three waves of unique longitudinal Adolescent Brain Cognitive Development Study data (ages 9-13) to test whether changes in cognition and structural neural metrics attenuate associations between genetic and environmental risk with persistent distressing PLEs. MethodsMultigroup univariate latent growth models examined three waves of cognitive metrics and global structural neural metrics separately for three PLE groups: persistent distressing PLEs (n=356), transient distressing PLEs (n=408), and low-level PLEs (n=7901). Models then examined whether changes in cognitive and structural neural metrics over time attenuated associations between genetic liability (i.e., schizophrenia polygenic risk scores/family history) or environmental risk scores (e.g., poverty) and PLE groups. ResultsPersistent distressing PLEs showed greater decreases (i.e., more negative slopes) of cognition and neural metrics over time compared to those in low-level PLE groups. Associations between environmental risk and persistent distressing PLEs were attenuated when accounting for lowered scores over time on cognitive (e.g., picture vocabulary) and to a lesser extent neural (e.g., cortical thickness, volume) metrics. ConclusionsAnalyses provide novel evidence for extant theories that worsening cognition and global structural metrics may partially account for associations between environmental risk with persistent distressing PLEs.

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