Network homeostasis: functional brain network alterations and relapse in remitted late-life depression

In this study, we aim to identify neurobiological factors that predict relapse risk in late-life depression (LLD). We recruited 145 older adults (age ≥ 60): 102 recently remitted LLD participants and 43 healthy comparisons. Participants underwent baseline MRI and evaluation of depression symptoms/status for up to 2 years. We evaluated intrinsic network connectivity for 111 participants (39 healthy comparisons, 47 stable remitted, 25 relapsed). LLD participants had lower connectivity primarily within and between the default mode (DMN), somatomotor, and visual networks and higher connectivity between the DMN and executive control network. Lower connectivity of DMN to somatomotor and salience networks was associated with relapse. Notably, the network structure of relapsed participants was more similar to healthy comparisons than stable remitted. These findings indicate that remission is associated with persistent functional network alterations while vulnerability to relapse may be associated with a failure to establish a new stable homeostatic functional network structure.