Treating Depression with Transcutaneous Auricular Vagus Nerve Stimulation: State of the Art and Future Perspectives

Jian Kong, Jiliang Fang, Joel Park, Shaoyuan Li, Peijing Rong, Jian Kong, Jiliang Fang, Joel Park, Shaoyuan Li, Peijing Rong

Abstract

Depression is a highly prevalent disorder, and its treatment is far from satisfactory. There is an urgent need to develop a new treatment for depression. Although still at its early stage, transcutaneous auricular vagus nerve stimulation (taVNS) has shown promising potential for treating depression. In this article, we first summarize the results of clinical studies on the treatment effect of taVNS on depression. Then, we re-analyze a previous study to identify the specific symptoms taVNS can relieve as indicated by subscores of the 24-item Hamilton Depression Scale in patients with depression. We found that taVNS can significantly reduce multiple symptoms of depression patients, including anxiety, psychomotor retardation, sleep disturbance, and hopelessness. Next, we pose several hypotheses on the mechanism of taVNS treatment of depression, including directly and indirectly modulating the activity and connectivity of key brain regions involved in depression and mood regulation; inhibiting neuro-inflammatory sensitization; modulating hippocampal neurogenesis; and regulating the microbiome-brain-gut axis. Finally, we outline current challenges and lay out the future directions of taVNS treatment of depression, which include (1) intensively comparing stimulation parameters and "dose effect" (treatment frequency and duration) to maximize the treatment effect of taVNS; (2) exploring the effect of taVNS on disorders comorbid with depression (such as chronic pain disorders, cardiovascular disorder, and autism) to provide new "two-for-one" treatment approaches for patients with these disorders; and (3) applying multiple scale methods to explore the underlying mechanism of taVNS.

Keywords: anti-inflammation; brain network; depression; transcutaneous auricular vagus nerve stimulation; transcutaneous vagus nerve stimulation; vagus nerve.

Figures

Figure 1
Figure 1
(A) Transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the brain network associated with the neuropathology of depression and inhibit inflammation response. Stimulation of the auricular branch of the vagus nerve (VN, indicated in red), which projects to the nucleus tractus solitari (NTS), continuing to the locus coeruleus and parabrachial nucleus. From the parabrachial nucleus, it propagates to various brain regions involved in depression (39, 40). taVNS may inhibit inflammation response to relieve stress and depressive symptoms. HTh, hypothalamus; PBN, parabrachial nucleus; LC, locus coeruleus; NTS, nucleus tractus solitary; DMNV, dorsal motor nucleus of the vagus nerve. (B) Auricular acupuncture points used for treating depression and other mental disorders at area with VN distribution.

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