Overall Focus
Major depressive disorder is one of the primary causes of disability worldwide with abnormalities in stress response circuitry and central autonomic brain circuitry. Many of these regions are sexually dimorphic and related to sex differences in mood and hypothalamic-pituitary-adrenal (HPA) axis modulation, the dysregulation of which is associated with increased cardiovascular risk.
Stimulation of the vagus nerve has emerged as a promising neuromodulatory technique with beneficial effects on regulating depressed mood, cardiovascular dysfunction, and inflammation. Non-invasive stimulation of the vagus nerve can be accomplished by transcutaneous stimulation (tVNS).
Our group has enhanced the effect by synchronizing the stimulation to respiration. This novel intervention may have significant effects in major depression, however, the mechanisms of action and neural pathways implicated are still unclear.
This study will identify the sex-dependent impact of non-invasive, respiratory-gated stimulation of the auricular branch of the vagus nerve on the modulation of stress response circuitry alterations and physiological dysregulation of recurrent depression.
Specific Aims
Aim 1
Identify the effects of respiratory-gated tVNS on modulation of brain stress circuitry in recurrent major depression.
Aim 2
Characterize effects of respiratory-gated tVNS on modulation of mood, vascular reactivity, cardiac autonomic and neurovascular function, HPA-axis activity and pro-inflammatory immune profile in recurrent major depression.
Aim3
Characterize the impact of sex on brain and physiological responses to respiratory-gated tVNS.
Our Senior Team
Key Discoveries by Our Group
Demonstrated sex-dependent alterations of the stress response circuitry associated with dysregulation of the HPA axis and cardiac autonomic physiology in subjects with major depression. (Garcia et al. 2020) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298013/)
Demonstrated that stimulation of the auricular branch of the vagus nerve gated to the exhalatory phase of the respiratory cycle results in enhanced modulation of vagal nuclei in the medulla such as nucleus of the tractus solitarii (NTS) and nucleus ambiguus (nAmb).
(Garcia et al. 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517046/)
(Sclocco et al 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592731/)
(Sclocco et al. 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931850/)
Found beneficial effects of respiratory-gated tVNS on modulation of depressed mood, anxiety symptoms and cardiac autonomic function in subjects with major depression and regulation of blood pressure levels in subjects with hypertension.
(Garcia et al. 2021, https://pubmed.ncbi.nlm.nih.gov/34365067/)
(Staley et al. 2020 https://pubmed.ncbi.nlm.nih.gov/33018534/