Revealing Changes in Linear and Nonlinear Functional Connectivity After Psilocybin and Escitalopram Treatment in Patients with Depression
bioRxiv (Cold Spring Harbor Laboratory) March 10, 2025 Shaun K.l. Quah, Cameron Glick, Leor Roseman et al. preprint
People with major depression who responded to either psilocybin or escitalopram showed distinct changes in brain network connectivity compared to non-responders. Responders had increased linear connectivity within the ventral attention network and greater nonlinear connectivity within the default mode and ventral attention networks. Psilocybin responders showed enhanced coordination between higher-order networks, while escitalopram responders showed reduced connectivity within networks linked to self-referential thought and salience processing. These patterns suggest the two antidepressants work through different mechanisms, with nonlinear connectivity analyses revealing effects not captured by traditional linear measures.