Structural Covariance Reveals Alterations in Control and Salience Network Integrity in Chronic Schizophrenia

Schizophrenia (SCZ) is recognized as a disorder of distributed brain dysconnectivity. While progress has been made delineating large-scale functional networks in SCZ, little is known about alterations in grey matter integrity of these networks. We used a multivariate approach to identify the structural covariance of the salience, default, motor, visual, fronto-parietal control, and dorsal attention networks. We derived individual scores reflecting covariance in each structural image for a given network. Seed-based multivariate analyses were conducted on structural images in a discovery (n = 90) and replication (n = 74) sample of SCZ patients and healthy controls. We first validated patterns across all networks, consistent with well-established functional connectivity reports. Next, across two SCZ samples, we found reliable and robust reductions in structural integrity of the fronto-parietal control and salience networks, but not default, dorsal attention, motor and sensory networks. Well-powered exploratory analyses failed to identify relationships with symptoms. These findings provide evidence of selective structural decline in associative networks in SCZ. Such decline may be linked with recently identified functional disturbances in associative networks, providing more sensitive multi-modal network-level probes in SCZ. Absence of symptom effects suggests that identified disturbances may underlie a trait-type marker in SCZ.