A Randomized Control Trial Treating Depression With Yoga and Coherent Breathing Versus Walking in Veterans

Overview The study tests the hypothesis that an imbalance in the autonomic nervous system
with to much sympathetic tone (Fight or Flight) and to little parasympathetic tone (rest,
renewal and social engagement) and associated low activity in the neurotransmitter gamma
aminobutyric acid (GABA) is associated with negative emotional states and may be a crucial
underlying link between negative emotions and poor health such that the correction of these
imbalances will be associated with decreased depressive symptoms in Veterans with Major
Depressive Disorder (MDD). Study Design: This is a Phase 2, longitudinal, efficacy,
randomized controlled trial. Veterans with MDD will be evaluated for eligibility and
randomized to 12-week intervention providing two-sessions per week of either an intervention
of yoga and coherent breathing at five breaths per minute or walking at 2.5 miles an hour,
such that the groups are matched for metabolic demand, interaction with research staff and
group effect. Depression scales will be collected at baseline and weeks 4, 8, and 12. Mood
scales and RSA will be collected at baseline and pre and post interventions at weeks 4, 8,
and 12. Magnetic resonance spectroscopy (MRS) data for thalamic GABA levels will be collected
at baseline (Scan 1), after the 12-week intervention (Scan 2) which is immediately followed
by the assigned intervention and Scan 3. The primary outcome measure is depression symptoms
assessed using established rating scales. The secondary outcome measure is the thalamic GABA
levels. The tertiary outcome measure is Respiratory Sinus Arrhythmia (RSA), a measure of high
frequency Heart Rate Variability and a marker of parasympathetic tone. Evaluations are
designed to address changes over the course of the study, and acute changes before and after
interventions at week 4, 8, and 12 evaluations. Instruments: Depression scales include the
Hamilton Rating Scale for Depression-17 (HDRS) and the Beck Depression Inventory II (BDI-II).
Mood scales include the Spielberger State -Trait Anxiety Inventory (STAI) and the Exercise
-Induced Feeling Inventory (EIFI). Post Traumatic Stress Disorder (PTSD) scales include the
Clinician Administered Posttraumatic Stress Scale (CAPS) and the PTSD Check List - Civilian
(PCL-C). Inclusion Criteria: The study will include 18 to 65 year old males and females
Veterans with a current diagnosis of MDD who have a HDRS scores to 14 at screening. If
subjects have been taking a stable dose of antidepressants that target a monoamine system for
at least three months with no anticipated changes during the study, they will be allowed to
continue their medication. Exclusion Criteria: The following are not allowed: history of
psychosis or bipolar illness; history of suicidal ideation with intent in the last year;
current mind-body practice (e.g., yoga, Tai Chi, Qigong, breathing practices, or meditation);
more than three current criteria for Alcohol or Substance Use Disorder using DSM-V criteria;
a current Substance Use Disorder, a neurologic or medical condition that could compromise
subject safety or the integrity of the study. Blinding: Individuals scoring the depression
scales, or analyzing the MRS and RSA data will be blind to group assignment. Hypothesis: I.a:
The yoga group but not the walking group will show decreased in depressive symptoms on the
HDRS and BDI-II from screening to week 12. 1.b: Subjects who are still depressed at baseline
despite treatment with a stable dose (> 3 months) of antidepressants treatment will show
decreased depressive symptoms in the yoga but not the walking group. 1.c: If present at
baseline, there will be a greater decrease in PTSD symptoms on the CAPS in the yoga compared
to the walking group. 2: There will be an increase in GABA levels over the course of the
three scans in the yoga but not the walking group. 3: Over the course of the intervention and
from pre to post-intervention at weeks 4, 8, and 12 there will be an improvement in the mood
scales (STAI and EIFI), and increase in RSA in the yoga but not the walking group.

Inclusion Criteria:

- Fluent in English

- Understands the risks and benefits of the study as listed in the Post Consent Quiz

- Females must agree to use an acceptable form of birth control [Human Subjects]

- Females are not pregnant and do not intend to become pregnant during the study

- Meets criteria for MDD on the MINI

- Hamilton Rating Scale for Depression (HDRS) scores to 14 at screening

- If subjects have been taking antidepressants that target a monoamine system, the dose
has been stable for at least three months with no anticipated changes during the study

- If subjects have been in a stable form of psychotherapy for three months, with no
anticipated changes in their psychotherapy during the study (this would exclude
time-limited manual-driven therapies such Cognitive Behavioral Therapy)

- Reliable contact information provided

- Has completed all required screening instruments and evaluations

Exclusion Criteria:

- History of psychosis

- History of bipolar illness

- History of suicidal ideation with intent and or a suicide attempt in the last year

- Desire to be treated for MDD with a new treatment during the study such as
pharmacotherapy, somatic therapy or psychotherapy

- Current mind-body practice defined as more than 6 one-hour sessions in the last 6
months

- yoga

- Tai Chi

- Qigong

- breathing practices, or meditation

- Participates in physical exercise > 5 hours/week that is equivalent to or greater than
6 metabolic equivalents (METs) in intensity

- Has been treated psychotropic medications such as mood stabilizers

- Valproic Acid

- Carbamazepine

- Lithium

- Benzodiazepines or pain medication other than Non Steroidal Anti-Inflammatory Drugs
(NSAIDS) in the last three months except for procedure related pain management

- dental procedures

- Has more than three current criteria for Alcohol or Substance Use Disorder using DSM-V
criteria

- Has a neurologic or medical condition that in the opinion of the PI could compromise
subject safety or the integrity of the study

- In the opinion of the PI, would not be expected to complete the study, or their
participation would be jeopardized subject safety or the integrity of the study

- Has an Axis-I diagnosis, other than depression except as listed, that in the opinion
of the PI would interfere with the subject's participation in this study

- Anxiety disorders with current symptoms that would impair participation in the study

- Obsessive Compulsive Disorder (OCD) or agoraphobia that would prevent
intervention attendance

- Post Traumatic Stress Disorder with dissociation or flashbacks that could be
triggered by the yoga intervention

- Claustrophobia that would prevent scanning

- Traumatic Brain Injury (TBI) with greater than 30 minutes loss of consciousness

- Must have a period of 48 hours of no alcohol use and 24 hours of no nicotine use on
TLFB to participate in scanning given the effects of tobacco smoke and alcohol
consumption on the GABA system