Twelve Year Longitudinal Trajectories Of Neuroanatomy, Functional Connectivity And Neuropsychological Function In 22Q11.2 Deletion Syndrome: Prediction To Psychosis

Abstract We conducted a twelve-year longitudinal study of neuroanatomic, neurofunctional and neuropsychological development in youth with 22q11.2 deletion syndrome (22q11DS). Participants, consisting of 88 youth with 22q11DS, 33 unaffected siblings, and 32 community controls, were recruited to our academic medical center from throughout North America, and were followed every three years for four timepoints. Mean age in years at the first timepoint was 11.9; second timepoint, 15.1; third timepoint, 18.1; fourth timepoint, 21.2. High resolution MRI scans and standard neuropsychological measures were administered at all timepoints. Trajectories of cortical thickness and surface area were measured with FreeSurfer, V.5.1. Functional connectivity (at the fourth timepoint only) was measured with the Functional Connectivity Toolbox (CONN) in Matlab. Positive symptoms of psychosis were measured with the Positive Symptom Subscale of the Structured Interview for Prodromal Symptoms (SIPS). Longitudinal linear mixed model regression analyses were conducted, and results were corrected for multiple comparisons. Relative to controls, probands displayed significantly slower rates of longitudinal change in cortical thickness of the superior parietal lobule and precuneus (p-values