Temporal dysregulation of the somatomotor network in agitated depression

Agitated depression (A-MDD) is a severe subtype of major depressive disorder, with an increased risk of suicidality and the potential to evolve into bipolar disorder. Despite its clinical significance, the neural basis remains unclear. We hypothesize that psychomotor agitation, marked by pressured speech and racing thoughts, is linked to disruptions in brain dynamics. To test this hypothesis, we examined brain dynamics using time delay estimation and edge-centre time series, as well as dynamic connections between the somatomotor network (SMN) and the default mode network in 44 patients with A-MDD, 75 with non-agitated MDD (NA-MDD), and 94 healthy controls. Our results revealed that the neural co-activity duration was shorter in the A-MDD group compared with both the NA-MDD and controls (A-MDD versus NA-MDD: t = 2.295; A-MDD versus controls: t = 2.192, all P < 0.05). In addition, the dynamic of neural fluctuation in SMN altered in the A-MDD group than in the NA-MDD group (t = -2.616, P = 0.011) and was correlated with agitation severity (beta = -0.228, P = 0.011). The inter-network connection was reduced in the A-MDD group compared with the control group (t = 2.102, P = 0.037), especially at low-amplitude time points (t = 2.139, P = 0.034). These findings indicate rapid neural fluctuations and disrupted dynamic coupling between the SMN and default mode network in A-MDD, potentially underlying the psychomotor agitation characteristic of this subtype. These insights contribute to a more nuanced understanding of the heterogeneity of depression and have implications for differential diagnosis and treatment strategies.