Major Depressive Disorder (MDD) affects up to 17% of the population and is not treated effectively in up to 40% of individuals. There is evidence that negative emotions are related to decreased activity in the parasympathetic nervous system (PNS) as measured by vagal tone. Both yoga practices and vagal nerve stimulation (VNS) can increase PNS activity by increasing vagal tone. Both yoga treatments and VNS have been shown to improve symptoms in depression and epilepsy. Using magnetic resonance spectroscopy (MRS), brain gamma-aminobutryic acid (GABA) levels have been shown to be low in subjects with MDD and epilepsy, and when the same subjects are treated with pharmacologic agents, GABA levels increase and symptoms decrease. Using MRS, our group has shown that thalamic GABA levels rise after a 60-minute yoga session and that increases in GABA levels are associated with improved mood. Our hypothesis is that low activity in the PNS and GABA systems is associated with depressive symptoms, and that a yoga intervention will stimulate the PNS afferents to brain stem nuclei, such that associated increases in GABA levels and decreased depressive symptoms will be observed. A dosing and feasibility study will be conducted prior to beginning the project. Aims: 1: To measure and compare baseline GABA levels in MDD and non-depressed healthy subjects (ND) in three anatomic structures, the thalamus, insula and hippocampal/amygdala complex. 2: To obtain four MRS scans in MDD subjects: Baseline (Scan 1); After 12- week yoga or walking interventions (Scan 2); Immediately after Scan 2, subjects will complete a 60-minute intervention (yoga or walking); Followed by Scan 3, and again two days after Scans 2 & 3 (Scan 4). 3: To measure changes in mood using psychological instruments and PNS activity using respiratory sinus arrhythmia (RSA) over the course of the study. Hypotheses: I: Baseline GABA levels will be lower in the MDD group compared to the ND group in all ROIs (i.e., thalamus, insula and hippocampal/amygdala complex). IIa & IIb: There will be a within-group change in tonic GABA levels (Scan 2-Scan 1) in the MDD subjects assigned to the yoga group. There will be a between-group difference in tonic GABA levels when comparing the MDD yoga group with the MDD walking group. IIIa & IIIb: There will be a within-group change in acute GABA levels (Scan 3-Scan 2) in the MDD yoga group. There will be a between-group difference in acute GABA levels when comparing the MDD yoga group with the MDD walking group. IV: There will be no change in recovery GABA levels (Scan 4 - Scan 2). V & VI: GABA levels, mood scales and RSA obtained at the time of scanning will be correlated, such that increasing GABA levels are associated with improved mood, decreased depression and decreased anxiety. VII: There will be a greater improvement in mood over the course of the interventions in the yoga group compared to the walking group.
NIH ExPorter
NIH ExPorter