Longitudinal development of thalamocortical functional connectivity in 22q11.2 deletion syndrome

Abstract

Background22q11.2 Deletion Syndrome (22qDel) is a genetic Copy Number Variant (CNV) that strongly increases risk for schizophrenia and other neurodevelopmental disorders. Disrupted functional connectivity between the thalamus and somatomotor/frontoparietal cortex has been implicated in cross-sectional studies of 22qDel, idiopathic schizophrenia, and youth at clinical high risk (CHR) for psychosis. Here, we use a novel functional atlas approach to investigate longitudinal age-related changes in network-specific thalamocortical functional connectivity (TCC) in 22qDel and typically developing (TD) controls. MethodsTCC was calculated for nine functional networks derived from resting-state functional magnetic resonance imaging (rs-fMRI) scans collected from n=65 22qDel participants (63.1% female) and n=69 demographically matched TD controls (49.3% female), ages 6 to 23 years. Analyses included 86 longitudinal follow-up scans. Non-linear age trajectories were characterized with general additive mixed models (GAMMs). ResultsIn 22qDel, TCC in the frontoparietal network increases until approximately age 13, while somatomotor and cingulo-opercular TCC decrease from age 6 to 23. In contrast, no significant relationships between TCC and age were found in TD controls. Somatomotor connectivity in 22qDel is significantly higher than TD in childhood, but lower in late adolescence. Frontoparietal TCC shows the opposite pattern. Conclusions22qDel is associated with aberrant development of functional network connectivity between the thalamus and cortex. Younger individuals with 22qDel have lower frontoparietal connectivity and higher somatomotor connectivity than controls, but this phenotype may normalize or partially reverse by early adulthood. Altered maturation of this circuitry may underlie elevated neuropsychiatric disease risk in this syndrome.