Longitudinal Analysis of Brain Function-Structure Dependencies in 22q11.2DS and Psychotic Symptoms.

BACKGROUND:Understanding how brain function and structure relate to one another, compared to conventional unimodal analysis, opens a new biologically-relevant assessment of neural mechanisms. However, how function-structure dependencies evolve throughout typical and abnormal neurodevelopment remains elusive. The 22q11.2 deletion syndrome (22q11.2DS) offers an important opportunity to study the development of function-structure dependencies and their specific association to the pathophysiology of psychosis. METHODS:Previously, we used graph signal processing to combine brain activity and structural connectivity measures in adults, quantifying functional-structural dependency (FSD). Here, we combined FSD with longitudinal multivariate partial least squares correlation (PLS-C) to evaluate FSD alterations across groups and among patients with and without mild to moderate positive psychotic symptoms (PPS). We assessed 391 longitudinally repeated resting-state functional and diffusion-weighted magnetic resonance imaging from 194 healthy controls and 197 deletion carriers (age span 7-34, data collected over a span of 12 years) RESULTS: Relative to controls, patients with 22q11.2DS showed a persistent developmental offset from childhood, with regions of hyper- and hypo-coupling across the brain. Additionally, a second deviating developmental pattern showed an exacerbation during adolescence, presenting hypo-coupling in frontal and cingulate cortex and hyper-coupling in temporal regions for patients with 22q11.2DS. Interestingly, the observed aggravation during adolescence was strongly driven by the PPS+ group. CONCLUSIONS:These results confirm a central role of altered FSD-maturation in the emergence of psychotic symptoms in 22q11.2DS during adolescence. The FSD deviations precede the onset of psychotic episodes and thus offer a potential early indication for behavioral interventions in individuals at risk.