Transcranial focused ultrasound as a possible treatment for major depression.

Antidepressants are currently used as initial therapies for major depressive disorder (MDD). However, despite the remarkable increase in medications validated as effective in MDD, treatments are still plagued by inadequate responses in part of MDD patients. For MDD with inadequate responses to medications, brain stimulation methods such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS) have been used as alternative strategies for treatment of depression, although each of these modalities has an indication for MDD treatment resistance and suffers from a limitation or weakness. Thus, development of new strategies based on novel theories of MDD may help to develop faster and more effective treatments for MDD. Recent studies have suggested that decreased brain brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of MDD. Moreover, increasing brain BDNF and adult hippocampal neurogenesis have been implicated in some of the therapeutic mechanisms of antidepressants. Transcranial focused ultrasound (tFUS), a novel technique to deliver highly focused acoustic energy to a small brain region, has been used for targeted drug delivery by increasing blood-brain barrier permeability, and it can noninvasively focally modulate human cortical function. Recent animal studies have demonstrated that tFUS stimulation can increase BDNF and neurogenesis in mice. Furthermore, the increase blood-brain barrier (BBB) permeability may increase delivery of serum BDNF to the brain. From the above evidence, tFUS can increase brain BDNF levels and neurogenesis in the hippocampus, suggesting it could be an alternative strategy for the treatment of MDD. Further investigations into the frequency and duration of tFUS stimulation are needed to verify the efficacy of this intervention in depressive disorders.