Differential Neural Dynamics in Psychomotor Retardation and Agitation of Depression

Psychomotor disturbances like agitation and retardation are key symptoms of major depressive disorder (MDD). Despite their clinical significance, the underlying neural mechanisms, for example, motor or psychomotor, remain yet elusive. This study aimed to investigate whether psychomotor agitation and retardation in MDD are associated with alterations in brain dynamics. A total of 119 patients with MDD and 94 HCs were recruited and undertaken fMRI testing. Brain dynamics was measured by the time delays, the lag propagation of global to somatomotor network (SMN) resting state functional connectivity (FC, e.g., lag propagation). Lag propagation of global to SMN FC was delayed in retarded MDD compared to both agitated MDD (t = 3.256, pFDR = 0.006) and HC (t = 2.493, pFDR = 0.041). Further, we observed a significant correlation of the severity of agitation and retardation, measured by the Hamilton depression scale, with global to local SMN's time delays, respectively (agitation: r = -0.19, p = 0.04; retardation: r = 0.32, p = 0.03). Finally, early global to SMN delays predicted a close association of agitation and anxiety levels (F = 5.18, p = 0.025). In contrast to these results in global-to-SMN dynamics, no significant delay changes were observed in the local intra-network SMN dynamics. Together, our findings show distinct neural dynamics in MDD psychomotor retardation, for example, delayed, and agitation, for example, early in global to local SMN functional connectivity. This supports the psychomotor over the motor model of psychomotor retardation which carries major implications for clinical diagnosis and therapy.