Distinct antidepressant therapies act on a common brain network

Depression disorder is a global health crisis, due to its high prevalence. Yet clinical treatments are inadequate. Uncovering the neural correlates of depression remission is a vital step toward developing effective therapies. Using a method termed therapeutic network mapping, we performed secondary analyses on the data of 16 longitudinal experiments and found that the network of the amygdala was commonly modulated by three antidepressant therapies (pharmacotherapy, electroconvulsive therapy, and magnetic seizure therapy). This therapeutic network was i) validated by two independent treatment datasets of patients with depression and a prospective preclinical experiment on male rats, ii) associated with networks of depression-related genes, neurotransmitters, and cognitions, and iii) also the target network of deep brain stimulation and repetitive transcranial magnetic stimulation (rTMS). Finally, a longitudinal rTMS experiment indicated that strengthened therapeutic network connectivity is associated with higher depressant alleviation. Taken together, our findings demonstrate that distinct antidepressant therapies act on a common network with potential targets for developing effective therapies.