Structural and Functional Neuroimaging Biomarkers as Predictors of Psychosis Conversion in Ultra-High Risk Individuals: A Systematic Review

Background: Approximately 20–30% of ultra-high risk (UHR) individuals transition to psychosis within 2–3 years. Neurobiological markers predicting conversion remain critical for precision prevention strategies. Objective: To systematically identify and evaluate structural and functional neuroimaging biomarkers at UHR baseline that predict subsequent conversion to psychosis. Methods: Following PRISMA 2020 guidelines, we searched five databases from January 2000 to February 2025. Two independent reviewers screened studies and assessed quality using the Newcastle–Ottawa Scale. Eligible studies examined baseline neuroimaging measures (structural MRI, functional MRI, diffusion tensor imaging, magnetic resonance spectroscopy) as predictors of psychosis conversion in UHR cohorts. Results: Twenty-five studies comprising 2436 UHR individuals (627 converters, 25.7%) were included (80.0% high quality). Reduced baseline gray matter volume in medial temporal structures (hippocampus: Cohen’s d = −0.45 to −0.68; parahippocampal gyrus: d = −0.52 to −0.71) and prefrontal cortex (d = −0.41 to −0.68) consistently predicted conversion. Progressive gray matter loss in superior temporal gyrus distinguished converters (d = −0.72). Reduced prefrontal–temporal functional connectivity predicted conversion (AUC = 0.73–0.82). Compromised white matter integrity in uncinate fasciculus (fractional anisotropy: d = −0.47 to −0.71) and superior longitudinal fasciculus predicted transition. Elevated striatal glutamate predicted conversion (d = 0.52–0.76). Thalamocortical dysconnectivity showed large effects (Hedges’ g = 0.66–0.88). Multimodal imaging models achieved 78–85% classification accuracy. Conclusions: Neuroimaging biomarkers, particularly medial temporal and prefrontal structural alterations, functional dysconnectivity, and white matter abnormalities, demonstrate moderate-to-large effect sizes in predicting UHR conversion. Multimodal approaches combining structural, functional, and neurochemical measures show promise for individualized risk prediction and early intervention targeting in precision prevention strategies.