Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome

Abstract

22q11.2 deletion syndrome (22q11.2DS) is a geneticneurodevelopmental disorder that represents one of thegreatest known risk factors for psychosis. Previous studies inpsychotic subjects without the deletion have identified a dopaminergic dysfunction in striatal regions, and dysconnectivityof striatocortical systems, as an important mechanism in theemergence of psychosis. Here, we used resting-state functional MRI to examine striatocortical functional connectivity in 22q11.2DS patients. We used a 2 × 2 factorial designincluding 125 subjects (55 healthy controls, 28 22q11.2DSpatients without a history of psychosis, 10 22q11.2DS patients with a history of psychosis, and 32 subjects with ahistory of psychosis without the deletion), allowing us toidentify network effects related to the deletion and to thepresence of psychosis. In line with previous results from psychotic patients without 22q11.2DS, we found that there wasa dorsal to ventral gradient of hypo- to hyperstriatocorticalconnectivity related to psychosis across both patient groups.The 22q11.2DS was additionally associated with abnormalfunctional connectivity in ventral striatocortical networks,with no significant differences identified in the dorsal system.Abnormalities in the ventral striatocortical system observedin these individuals with high genetic risk to psychosis maythus reflect a marker of illness risk.