ArticleBiological psychiatry global open science2026
Developmental Brain Network Trajectories Differentiate Resilience and Vulnerability to Psychosis in 22q11.2 Deletion Syndrome.
Article in Biological psychiatry global open science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Disrupted maturation of functional brain networks has been increasingly linked to elevated risk of psychosis, but the spatiotemporal characteristics of these deviations remain unclear. We used longitudinal connectome fingerprinting and jointly analyzed the functional connectivity (FC) and intraclass correlation coefficient (ICC) to obtain age-dependent trajectories of functional brain organization in 22q11.2 deletion syndrome (22q11DS), a high-risk model for psychosis. Methods: Resting-state functional magnetic resonance imaging from 62 individuals with 22q11DS and 63 control participants (ages 8-30 years, 2-5 visits) were analyzed. Patients were stratified by the presence or absence of positive psychotic symptoms (PPSs) [PPS(+), PPS(-)]. The FC and ICC characterization of connectome fingerprints were projected onto a joint principal component (PC) space, yielding 3 orthogonal axes of maturation: PC1 (sensory-association axis), PC2 (emotional-cognitive balance), and PC3 (executive-sensory control). Longitudinal trajectories along these axes characterized the directionality and coordination of connectome maturation. Results: Control participants showed a clear decrease in identifiability and stability during adolescence, followed by recovery into adulthood, reflecting coordinated, direct maturation along all 3 axes. PPS(-) individuals exhibited a partial decrease and subsequent recovery, preserving adaptive reorganization along PC3. In contrast, PPS(+) participants displayed disorganized and irregular trajectories in the PC space and a decline in PC3, indicating disrupted temporal coordination of network maturation and fragmented executive-sensory integration. Conclusions: Loss of developmental synchrony in FC was associated with psychosis vulnerability in 22q11DS. PC analysis-based multiaxis mapping revealed that resilience and vulnerability are determined by the direction and synchrony of brain maturation rather than by stability alone, highlighting a novel marker for tracking neurodevelopmental risk across psychiatric disorders.
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