Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder.
ABSTRACT A theory is proposed to explain the benefits of yoga practices in diverse, frequently comorbid medical conditions based on the concept that yoga practices reduce allostatic load in stress response systems such that optimal homeostasis is restored. It is hypothesized that stress induces (1) imbalance of the autonomic nervous system (ANS) with decreased parasympathetic nervous system (PNS) and increased sympathetic nervous system (SNS) activity, (2) underactivity of the gamma amino-butyric acid (GABA) system, the primary inhibitory neurotransmitter system, and (3) increased allostatic load. It is further hypothesized that yoga-based practices (4) correct underactivity of the PNS and GABA systems in part through stimulation of the vagus nerves, the main peripheral pathway of the PNS, and (5) reduce allostatic load. Depression, epilepsy, post traumatic stress disorder (PTSD), and chronic pain exemplify medical conditions that are exacerbated by stress, have low heart rate variability (HRV) and low GABAergic activity, respond to pharmacologic agents that increase activity of the GABA system, and show symptom improvement in response to yoga-based interventions. The observation that treatment resistant cases of epilepsy and depression respond to vagal nerve stimulation corroborates the need to correct PNS underactivity as part of a successful treatment plan in some cases. According to the proposed theory, the decreased PNS and GABAergic activity that underlies stress-related disorders can be corrected by yoga practices resulting in amelioration of disease symptoms. This has far-reaching implications for the integration of yoga-based practices in the treatment of a broad array of disorders exacerbated by stress.
- SourceAvailable from: Kenneth G Walton[show abstract] [hide abstract]
ABSTRACT: Stress has been implicated in both somatic and mental disorders. The mechanisms by which stress leads to poor health are largely unknown. However, studies in animals suggest that chronic stress causes high basal cortisol and low cortisol response to acute stressors and that such changes may contribute to disease. Previous studies of the Transcendental Mediation® (TM) technique as a possible means of countering effects of stress have reported altered levels of several hormones both during the practice and longitudinally after regular practice of this technique. In this prospective, random assignment study, changes in baseline levels and acute responses to laboratory stressors were examined for four hormones—cortisol, growth hormone, thyroid-stimulating hormone and testosterone—before and after 4 months of either the TM technique or a stress education control condition. At pre- and post-test, blood was withdrawn continuously through an indwelling catheter, and plasma or serum samples were frozen for later analysis by radioimmunoassay. The results showed significantly different changes for the two groups, or trends toward significance, for each hormone over the 4 months. In the TM group, but not in the controls, basal cortisol level and average cortisol across the stress session decreased from pre- to post-test. Cortisol responsiveness to stressors, however, increased in the TM group compared to controls. The baselines and/or stress responsiveness for TSH and GH changed in opposite directions for the groups, as did the testosterone baseline. Overall, the cortisol and testosterone results appear to support previous data suggesting that repeated practice of the TM technique reverses effects of chronic stress significant for health. The observed group difference in the change of GH regulation may derive from the cortisol differences, while the TSH results are not related easily to earlier findings on the effects of chronic stress.Psychoneuroendocrinology 06/1997; · 5.14 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Yoga teachers and students often report that yoga has an uplifting effect on their moods, but scientific research on yoga and depression is limited. To examine the effects of a short-term Iyengar yoga course on mood in mildly depressed young adults. Young adults pre-screened for mild levels of depression were randomly assigned to a yoga course or wait-list control group. College campus recreation center. Twenty-eight volunteers ages 18 to 29. At intake, all participants were experiencing mild levels of depression, but had received no current psychiatric diagnoses or treatments. None had significant yoga experience. Subjects in the yoga group attended two 1-hour Iyengar yoga classes each week for 5 consecutive weeks. The classes emphasized yoga postures thought to alleviate depression, particularly back bends, standing poses, and inversions. Beck Depression Inventory, State-Trait Anxiety Inventory, Profile of Mood States, morning cortisol levels. Subjects who participated in the yoga course demonstrated significant decreases in self-reported symptoms of depression and trait anxiety. These effects emerged by the middle of the yoga course and were maintained by the end. Changes also were observed in acute mood, with subjects reporting decreased levels of negative mood and fatigue following yoga classes. Finally, there was a trend for higher morning cortisol levels in the yoga group by the end of the yoga course, compared to controls. These findings provide suggestive evidence of the utility of yoga asanas in improving mood and support the need for future studies with larger samples and more complex study designs to more fully evaluate the effects of yoga on mood disturbances.Alternative therapies in health and medicine 01/2004; 10(2):60-3. · 1.77 Impact Factor
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ABSTRACT: Using 1H spectroscopy, we measured occipital lobe GABA levels serially in 18 patients enrolled in an ongoing open label trial of vigabatrin. Brain GABA levels were elevated twofold in patients taking vigabatrin (3 to 4 g/d) compared with nonepileptic subjects. Serial measurements suggested that brain GABA rose in proportion to vigabatrin dose up to 3 g/d. Doubling the dose from 3 to 6 g/d failed to increase brain GABA further. Serial measurements on three patients taking 6 g/d showed a gradual decrease in brain GABA in two patients over 1 to 2 years of treatment. These observations suggest that GABA synthesis may decrease at high GABA levels.Neurology 06/1996; 46(5):1459-63. · 8.25 Impact Factor
Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and
allostasis in epilepsy, depression, and post-traumatic stress disorder
C.C. Streetera,⇑, P.L. Gerbargb, R.B. Saperc, D.A. Cirauloa, R.P. Brownd
aDepartment of Psychiatry, Boston University School of Medicine, Boston, MA, United States
bDepartment of Psychiatry, New York Medical College, Vahlia, NY, United States
cDepartment of Family Medicine, Boston University School of Medicine, Boston, MA, United States
dDepartment of Psychiatry, Columbia University, College of Physicians and Surgeons, NY, United States
a r t i c l e i n f o
Received 29 November 2011
Accepted 10 January 2012
a b s t r a c t
A theory is proposed to explain the benefits of yoga practices in diverse, frequently comorbid medical
conditions based on the concept that yoga practices reduce allostatic load in stress response systems such
that optimal homeostasis is restored. It is hypothesized that stress induces (1) imbalance of the auto-
nomic nervous system (ANS) with decreased parasympathetic nervous system (PNS) and increased sym-
pathetic nervous system (SNS) activity, (2) underactivity of the gamma amino-butyric acid (GABA)
system, the primary inhibitory neurotransmitter system, and (3) increased allostatic load. It is further
hypothesized that yoga-based practices (4) correct underactivity of the PNS and GABA systems in part
through stimulation of the vagus nerves, the main peripheral pathway of the PNS, and (5) reduce allostat-
ic load. Depression, epilepsy, post traumatic stress disorder (PTSD), and chronic pain exemplify medical
conditions that are exacerbated by stress, have low heart rate variability (HRV) and low GABAergic activ-
ity, respond to pharmacologic agents that increase activity of the GABA system, and show symptom
improvement in response to yoga-based interventions. The observation that treatment resistant cases
of epilepsy and depression respond to vagal nerve stimulation corroborates the need to correct PNS
underactivity as part of a successful treatment plan in some cases. According to the proposed theory,
the decreased PNS and GABAergic activity that underlies stress-related disorders can be corrected by
yoga practices resulting in amelioration of disease symptoms. This has far-reaching implications for
the integration of yoga-based practices in the treatment of a broad array of disorders exacerbated by
? 2012 Elsevier Ltd. All rights reserved.
A unifying theory is proposed to explain the effects of yoga in
medical conditions with overlapping pathophysiologies based on
the principle that yoga practices reduce allostatic load in stress re-
sponse systems and restore optimal homeostasis. It is hypothe-
sized that stress induces: (1) imbalance of the autonomic
nervous system (ANS) with decreased parasympathetic nervous
system (PNS) increased sympathetic nervous system (SNS) activity,
(2) underactivity of the inhibitory neurotransmitter, gamma ami-
no-butyric acid (GABA) and (3) increased allostatic load. It is fur-
ther hypothesized that yoga practices (4) correct underactivity of
the PNS and GABA system in part through stimulation of the vagal
nerves and (5) reduce allostatic load resulting in symptom relief.
Depression, epilepsy, post traumatic stress disorder (PTSD), and
chronic pain exemplify conditions that are exacerbated by stress,
have low PNS and low GABA system activity, respond to pharmaco-
logic agents that increase activity of the GABA system, and improve
in response to yoga-based interventions. It is proposed that as
yoga-based interventions support the return towards optimal bal-
ance in the PNS and GABA system, function improves in regions of
the brain that regulate response to threat, such as threat percep-
tion, interoception, fear processing, emotion regulation, and defen-
sive reactions. As central regulatory systems become more
balanced and flexible, allostatic load is reduced leading to health
Neurophysiological foundations and evidence
The brain determines what is threatening and therefore stress-
ful. Stress response involves two-way communication between the
0306-9877/$ - see front matter ? 2012 Elsevier Ltd. All rights reserved.
⇑Corresponding author. Address: Boston University School of Medicine, 85 E.
Newton St., M912E, Boston, MA 02118, United States. Tel.: +1 617 638 6422; fax: +1
617 638 8008.
E-mail address: firstname.lastname@example.org (C.C. Streeter).
Medical Hypotheses 78 (2012) 571–579
Contents lists available at SciVerse ScienceDirect
journal homepage: www.elsevier.com/locate/mehy
brain and the cardiovascular, immune, metabolic and other sys-
tems via the nervous system, endocrine system and hypotha-
lamic–pituitary–adrenal (HPA) axis . Homeostasis refers to the
mechanisms that keep the parameters of an organism’s internal
milieu within the ranges necessary for survival . In this discus-
sion, optimal homeostasis is considered to be the state in which
meeting the immediate needs of the organism incurs the least pos-
sible long-term costs. McEwen (2007) proposes that allostasis is
the adaptive process of maintaining stability during conditions
that are outside of the usual homeostatic range . Allostatic load
is the cost to the body for maintaining this stability during devia-
tions from the usual homeostatic range, often reflected in patho-
physiological conditions and disease progression . Physiologic
systems activated by stress can both protect the body in the short
term and damage the body in the long term , especially when
stress becomes chronic and an allostatic load is incurred. For exam-
ple, increased SNS activity with elevated blood pressure and heart
rate in response to real or perceived threat is beneficial in the short
term for survival, but sustained high SNS activity incurs harmful
long term effects such as hypertension, atherosclerotic disease
and cardiac morbidity .
Stress activated systems and disorders
The proposed theory states that stress from psychological,
physically external and physically internal sources results in allo-
static load, which can be reduced by yoga-based practices that shift
regulatory systems towards optimal homeostasis. This theory can
encompass allostatic load on the following stress activated sys-
tems: ANS, neuroendocrine, HPA axis, cardiovascular, metabolic
and immune . Overactivity or underactivity of stress responsive
systems is associated with increased symptoms in a wide range of
disorders including: psychiatric disorders such as depression, anx-
iety, PTSD [5,6], alcohol and other substance dependence ; neu-
rologic disorders such as epilepsy  and chronic pain ;
cardiovascular disorders such as hypertension, vascular disease
and myocardial infarction [10,11]; metabolic disorders such as
metabolic syndrome, diabetes, and obesity ; and immune dis-
orders such as infection, cancer and asthma . These stress-
exacerbated disorders include four of the major causes of mortality
in the U.S., heart disease, cancer, stroke and diabetes , plus
three major causes of morbidity, depression, anxiety disorders,
and chronic pain . The above disorders improve in response
to yoga-based therapies underscoring the far-reaching implica-
tions of the proposed theory .
The rationale for the proposed theory will be developed by
focusing on the effects of stress-induced allostatic load on the
autonomic and GABA systems and the reduction of allostatic load
by yoga-based practices in the treatment of epilepsy, major
depressive disorder (MDD), PTSD, and chronic pain. These four se-
lected disorders have the following common characteristics: exac-
erbation by stress; low parasympathetic tone as measured by low
heart rate variability (HRV); low GABAergic activity; improvement
when treated with pharmacologic agents that increase activity of
the GABA system; and improvement in response to yoga based
therapies [8,17–35]. According to the proposed theory ANS imbal-
ance with decreased PNS activity and increased SNS activity is
important in the pathogenesis of epilepsy, MDD, PTSD, and chronic
pain. This ANS imbalance is also associated with underactivity in
the GABA system. Furthermore, stimulation of the vagus nerves
by yoga-based practices corrects PNS underactivity leading to cor-
rection of GABA underactivity. Although reduction of overactivity
of the SNS by yoga contributes to balancing the stress response
systems, this discussion will focus on the PNS. The term ‘GABAer-
gic’ indicates activity of the GABA system detectable by various
methods of measurement. For the purpose of this paper the term
‘yoga’ is used to encompass ancient and modern mind–body tech-
niques, including all forms of yoga and other traditions that incor-
porate postures, meditation, chanting or breathing techniques.
Anatomy of the autonomic nervous system
The ANS is comprised of the SNS and the PNS. The main periph-
eral pathways of the PNS are within the vagus nerves . Each va-
(transmitting signals from the central nervous system (CNS) to
the body) and three afferent fiber groups (transmitting information
from the body to the CNS). The first group of vagal efferents, unmy-
elinated General Visceral Efferent (GVE) fibers, originates in the
dorsal motor nucleus (DMN) and predominately innervates tho-
racic and abdominal viscera. DMN fibers regulate subdiaphrag-
matic organs, but do not play a significant role in cardiac
function . The second group of vagal efferents, myelinated Spe-
cial Visceral Efferent (SVE) fibers originating in the nucleus ambig-
uous (NA) innervate the pharynx, larynx, lungs, heart, and other
viscera . SVE fibers deliver inhibitory input to the sinoatrial
node, slowing the heart rate .
The majority of afferent vagal fibers are General Visceral Affer-
ents (GVA) that carry information from the pharynx, larynx, tra-
chea, and viscera of the thorax and abdomen to the nucleus
tractus solitarius (NTS) . The second group of afferent fibers,
General Somatic Afferents (GSA), carries sensations from the skin
in the auditory meatus and taste receptors to synapse in the spinal
trigeminal tract . The third group of afferent fibers, Special Vis-
ceral Afferents (SVA), carries sensory taste information to the NTS
. As the main terminus for GVA fibers, the NTS is an important
relay station providing the brain with information about the body’s
internal milieu [37,39]. The NTS has connections to autonomic,
reticular and limbic structures via projections to the parabrachial
nucleus (PBN), periacqueductal grey, central nucleus of the amyg-
dala (CEA), hippocampus, hypothalamus, and thalamus . The
PBN sends projections to the thalamus, CEA, basolateral nucleus
of the amygdala (BLA), hypothalamus, anterior insula, and prefron-
tal cortex . Craig describes these neural connections as convey-
ing information from the vagus nerves to the structures that
mediate interoceptions (perceptions of the internal state of the
body), threat perceptions and affective states . Through this
network, vagal activity influences emotional states and thought
processes as well as their somatic expression (See Fig. 1).
Polyvagal theory and heart rate variability (HRV)
The polyvagal theory described by Porges identifies three phy-
logenetic developments in neural regulation of the ANS . The
oldest part, the unmyelinated visceral vagus, responds to threat
by depressing metabolic activity. The next developmental stage,
the SNS, is capable of increasing metabolic output and mobilization
behaviors necessary for ‘fight or flight’. The third and most ad-
vanced pathway, the myelinated vagus, promotes calm states con-
sistent with the metabolic demands of growth, repair, and
restoration. The myelinated vagus, found only in mammals, sup-
ports social engagement and engenders feelings of safety. Myelin-
ated vagal efferent fibers from the NA serve as the vagal brake,
which enables rapid control of heart rate (HR) by increasing vagal
tone to reduce HR and blood pressure or decreasing vagal tone to
accelerate heart rate . Heart rate variability (HRV) refers to
changes in the heart’s beat-to-beat intervals. Vagal control allows
more rapid adjustments in HR and thus greater HRV than does
SNS control, which takes longer to turn on and longer to turn off
C.C. Streeter et al./Medical Hypotheses 78 (2012) 571–579
. Accordingly, high HRV implies vagal dominance and is a sign
that the stress response system has greater flexibility to respond to
challenges . Conversely, low HRV, indicating more restricted
responsiveness, is associated with increased risk of all-causes of
mortality related to cardiac disease . An organism’s response
to internal and external challenges is limited by the need to main-
tain stability. When stability is maintained through allostasis, flex-
ibility of the system declines and leads to pathological states and
damage to the organism.
of the ANS, which affords the greatest flexibility of response. When
cruited to regulate metabolic output in response to stress . This
calm, resting, reparative, anti-inflammatory state when the threat
has ceased . Thus underactivity of the PNS, manifested by de-
dependence on sympathetic excitation of the cardiovascular and
sion, hyperarousal, and over reactivity .
The role of the vagus in social interactions in polyvagal theory is
extended in the neurovisceral integration model of affect regula-
tion described by Thayer, which proposes that dysfunctional psy-
chological states are rooted in an impaired vagal inhibitory
mechanism associated with low HRV [44,45]. Neurovisceral inte-
gration suggests that ANS imbalance, particularly with underactiv-
ity of the PNS, may be the final common pathway between
negative emotions and poor health .
How yoga increases PNS activity
Although there are many kinds of yoga practices, the relation-
ship between yoga and PNS activity is most easily demonstrated
by yogic breathing. Emotional states affect respiratory rate, depth
and pattern. Conversely, voluntary changes in the pattern of breath
can account for 40% of the variance in feelings of anger, fear, joy
and sadness . Breathing is controlled by voluntary and involun-
tary mechanisms. Voluntarily controlled breathing patterns can af-
fect the ANS and HRV [47,48].
The neurophysiologic model for the effects of yoga breathing
Brown and Gerbarg describe a neurophysiologic model for the
effects of yoga breathing in which stretch receptors in the alveoli,
baroreceptors, chemoreceptors, and sensors throughout the respi-
ratory structures send information about the state and activity of
the respiratory system through vagal afferents and brainstem relay
stations to other CNS structures where they influence perception,
cognition, emotion regulation, somatic expression, and behavior
[49–52]. The fact that breathing is the only autonomic function
that can easily be voluntarily controlled provides a portal through
which specific selected breathing patterns can be used to send
messages through PNS, SNS and interoceptive systems to affect
how the brain perceives, interprets, and responds to stress or
threat. Because breathing is vital to survival, information from
the respiratory system must be noticed and attended to immedi-
ately. Therefore, their model suggests that signals from vagal affer-
ents carrying information about changes in the rate, depth, or
pattern of breathing receive the highest priority and have rapid,
widespread effects on brain functions. Brown and Gerbarg have re-
viewed the evidence that yoga-breathing interventions increase
HRV, improve sympatho-vagal balance, and promote stress resil-
ience [49–51]. For example, Coherent Breathing and Resonant
Breathing, using a fixed rate of three and a half to six breaths per
minute (bpm), increase HRV and PNS activity [53–55]. Ujjayi
(Ocean Breath) is one form of resistance breathing that uses laryn-
geal contracture and partial closure of the glottis to impede the
flow of air. Resistance breathing techniques increase intrathoracic
pressure, baroreceptor stimulation, respiratory sinus arrhythmia
(RSA), and HRV . Using breath-holds with Ujjayi further in-
crease PNS activity . The ancient ‘Om’ chant involves slow
Fig. 1. Neuroanatomic Connections of Parasympathetic Nervous System with GABA System.
C.C. Streeter et al./Medical Hypotheses 78 (2012) 571–579
breathing, airway resistance (contracting the vocal cords to gener-
ate sound), which increase vagal tone and physiologic relaxation
. Using fMRI, Kalyani, Gangadhar, and colleagues showed sig-
nificant limbic system deactivation with ‘OM’ chanting .
Experienced Qigong trainees have higher HRV than age-matched
sedentary controls . Increases in HRV have been documented
with an Iyengar yoga intervention compared to a walking control
. The pattern of slow resistance breathing with longer periods
of exhalation than inhalation occurs during chanting, singing, and
mind–body practices in many traditions. Bernardi suggested that a
respiratory rate of 6 bpm augments 10-s (6/min) Mayer waves and
increases the effect of respiratory sinus arrhythmia (RSA), a mea-
surement correlated with HRV . Bernardi also found that reci-
tation of the rosary prayer in Latin at 6 bpm increased HRV and
baroreflex sensitivity . The appearance of similar respiratory
rates in breathing, chanting, and meditative practices across cul-
tures supports the theory that these techniques reduce imbalances
in the ANS leading to improved mood, decreased anxiety and im-
proved health [49–51].
Yoga practices associated with decreased cortisol
Cortisol levels and brain GABA levels are biologic markers of
stress [62,63]. Elevated corticotrophin releasing factor and cortisol
levels found in depression, PTSD and epilepsy indicate increased
HPA axis activity [5,6,64]. These three disorders also show evi-
dence for decreased activity in the GABA system [23–25]. De-
creased cortisol levels have been reported after interventions
using yoga postures and meditation [65–68]. In a study of Tran-
scendental Meditation (TM), participants with 3–5 years of experi-
ence had significantly greater decreases in cortisol levels than
novices with 3–4 months of TM experience . Symptoms of epi-
lepsy and depression can be ameliorated with either yoga inter-
ventions or pharmacologic agents that increase activity of the
GABA system directly (e.g. anti-epileptic drugs) or indirectly (e.g.
Selective Serotonin Reuptake Inhibitors—SSRIs) [27,31–35,69,70].
The proposed theory that stress-induced allostatic load is associ-
ated with increased symptoms in depression, PTSD, and epilepsy
is buttressed by evidence of increased HPA axis activity and de-
creased GABAergic activity. Studies also suggest that yoga practices
reduce stress-induced allostatic load in three stress reactive sys-
tems: the ANS, the HPA axis, and the GABAergic system (see Fig. 3).
Vagal nerve stimulation (VNS) addresses low PNS and GABA activity
VNS has been approved by the Federal Drug Administration for
treatment resistant epilepsy and depression [36,71]. VNS provides
an evidential link between peripheral stimulation of the vagus
nerve and activation of brain regions that are modulated by GABA.
Functional imaging studies show that VNS activates brain regions
involved in cognition, emotion and affect. In epileptic and normal
subjects respectively, VNS and transcutaneous vagal nerve stimu-
lation (t-VNS) via GSA fibers in the auditory meatus were associ-
ated with functional changes in the thalamus, amygdala, insula,
hippocampus, parahippocampal gyrus and prefrontal regions
[40,72,73]. It is plausible that the beneficial effects of VNS in treat-
ment resistant epilepsy and depression are mediated in part by
normalization of an ANS imbalance that was not corrected by prior
Vagal nerve stimulation (VNS) and neurotransmitters
VNS increases neurotransmitter levels in systems implicated in
the treatment of epilepsy and depression: GABA, norepinephrine
(NE), and serotonin . Vagal afferents influence the noradrener-
gic locus ceruleus (LC), the serotonergic dorsal raphe nuclei, and
GABA release via the NTS [36,74]. The antiepileptic effect of VNS
is thought to be in part due to widespread release of GABA in the
brainstem and cortex . Gamma-vinyl-gamma-aminobutyric
acid (GVG), an irreversible inhibitor of GABA transaminase, in-
creases GABA levels by reducing the metabolism of GABA. The
injection of GVG into the thalamus, hypothalamus and bulbar re-
gions blocks pentylenetetrazol (PTZ) induced seizures . PTZ in-
duced seizures are also blocked by VNS . Yoga-based therapies
have been associated with increased PNS activity, increased GABA
levels, and reduced symptoms in epilepsy and MDD [31,32,75].
These observations are consistent with the theory that VNS and
yoga-based therapies could decrease seizures and depressive
symptoms by increasing PNS activity that in turn increases GABA
Stress, medial temporal lobe, GABA and hypothalamic–pituitary–
adrenal axis (HPA)
Neural circuits that mediate effects of the ANS and HPA axis
converge in the hippocampus, a component of the limbic system.
Vagal nerve projections to the NTS are relayed to the amygdala di-
rectly as well as indirectly via the PBN . Through connections in
the LC, PBN input reaches the hippocampus . Embedded in the
medial temporal lobe, the amygdala and hippocampus are vital for
memory function, emotion processing, mediation of psychological
stress, and modulation of HPA response to stress [1,38,77]. The hip-
pocampus is essential for declarative memory while the amygdala
is essential for threat perception and emotional memory . To-
gether they contribute to the retention and influence of significant
memories . The hippocampus plays a major role in the percep-
tion of threat, the experience of stress, and memory functions via
its interactions with the PNS, HPA axis and GABA systems. Individ-
uals with PTSD have been shown to have impaired declarative
memory and reduced hippocampal volume . Within the hippo-
campus the presence of high concentrations of both mineralocorti-
coid and glucocorticoid receptors is indicative of its role in stress
experience and threat perception . The HPA axis response to
stress begins when the paraventricular nucleus (PVN) of the hypo-
thalamus secretes corticotrophin-releasing hormone (CRH) carried
via the portal system to the anterior pituitary lobe where it binds
to CRH receptors and stimulates secretion of adrenocorticotrophic
hormone (ACTH), which induces the adrenal glands to release min-
eralocorticoids and glucocorticoids . CRH receptors are also
found in the hypothalamus, amygdala, hippocampus, basal nucleus
of the striatum (BNST), central gray area, locus ceruleus (LC), par-
abrachial nucleus (PBN), dorsal vagal nucleus, prefrontal cortex
and anterior cingulate gyrus [5,80]. Chronic stress results in
Fig. 2. Mean thalamic GABA levels in subjects with Major Depressive Disorder
(MDD) and low back pain (LBP) (n = 2) compared to normal subjects (n = 19) before
(Scan 1) and after (Scan 2) a 12-week yoga intervention.
C.C. Streeter et al./Medical Hypotheses 78 (2012) 571–579
prolonged increases in glucocorticoid levels . High levels of cir-
culating glucocorticoids provide negative feedback that reduces
PVN synthesis of CRH, but activates CRH release in the central nu-
cleus of the amygdala (CEA) . The action of CRH in the amygdala
constitutes an additional mechanism for mediating autonomic and
behavioral responses to stress including the promotion of anxiety,
fear-based behaviors, and defensive reactions [5,7]. Stress is asso-
ciated with neuronal pruning and volume reduction in the hippo-
campus, which results in prolongation of HPA axis response to
stress [1,79]. In contrast, stress leads to increased dendritic branch-
ing in the amygdala . In summary, lesions of the hippocampus
increase HPA axis response, whereas lesions in the medial amyg-
dala decrease HPA axis response. Accordingly, there is a reduction
in hippocampal function, reflected in decreased declarative mem-
ory, and an amplification in amygdala activity evidenced by in-
creased fear response to behavioral stress .
Stress is associated with decreased hippocampal GABA levels
. Used as a model for depression, inescapable shock is associ-
ated with decreased hippocampal GABA levels . The same
behavior seen after inescapable shock can be produced by injec-
tions of the GABAAantagonist, bicuculline . As cortisol levels
rise, the frequency of GABA receptor mediated synaptic events de-
clines . In contrast GABAAagonists, such as benzodiazepines,
that increase GABAergic activity, are used to reduce anxiety. The
benzodiazepine, alprazolam, inhibits the activity of the HPA by
blunting increases in CRH, ACTH and cortisol [84,85]. A cholecysto-
kinin-tetrapeptide (CCK-4) challenge induces panic attacks in pa-
tients with panic disorder and in healthy volunteers . CCK-4
panic attacks are associated with increased ACTH and cortisol lev-
els. Subjects pre-treated with the GABA agonists, alprazolam and
vigabatrin, before a CCK-4 challenge showed decreased symptoms
of panic and blunted response of ACTH and cortisol [86,87]. These
studies are consistent with the proposed theory, that increased
activity in the GABA system associated with yoga-based practices
would decrease anxiety and stress reactivity.
HPA axis abnormalities, as indicated by higher CRH levels in
cerebrospinal fluid (CSF), have been found in PTSD subjects .
Compared to normal controls, individuals with PTSD can have low-
er PNS tone, higher cardiac SNS activity, and decreased activity in
the GABA system [19–21]. In humans low plasma GABA levels after
a traumatic event predict the development of PTSD . Trans-
magnetic stimulation studies of individuals with PTSD revealed
bilateral decreases in the GABAAsystem activity . Functional
imaging studies of PTSD subjects have documented decreased ben-
zodiazepine-GABAAreceptor binding in the prefrontal cortex (PFC),
hippocampus, amygdala, and thalamus, the same regions that are
affected by VNS, suggesting an association between the GABA
and ANS systems [25,40,72,73,90].
Decreases in benzodiazepine binding in regions of the brain
known to support emotions and affect are consistent with abnor-
malities seen in imaging studies of individuals with PTSD. Positron
Emission Tomography (PET) studies of PTSD subjects show de-
creased activation of the medial PFC and increased activation of
the amygdala in response to the reading of trauma related scripts
and threatening faces . A similar pattern is seen in individuals
with a genetic predisposition to depression, who show increased
left amygdala activation in response to threatening faces .
Yoga treatment for epilepsy
Stress is associated with increased seizure frequency . Most
adults with poorly controlled seizures have complex partial sei-
zures with a temporal lobe focus . As part of the limbic system,
medial temporal lobe structures including the amygdala, hippo-
campus and entorhinal cortex are considered to be an anatomical
link between emotional stress and its neurophysiological conse-
quences [10,94]. Eggers theorized that resonator neurons, which
process information from sensory stimuli and other neurons, are
at increased risk for epileptogenic discharge during psychological
stress due to inputs from the circuit of emotion which includes
the hippocampus, amygdala, entorhinal cortex and dorsal raphe
nucleus . Evidence that stress can increase seizure frequency
is consistent with the hypotheses that stress-induced allostatic
load leads to pathological conditions such as increased seizure
activity. According to the neurovisceral integration theory, stress
is associated with impaired vagal tone, decreased HRV, and poor
health. Furthermore, studies show that individuals with epilepsy
have low HRV, greater risk of sudden death, and increased morbid-
ity . Therefore, the reduction of seizure frequency by yoga prac-
tices may be attributable to increased vagal tone and GABA
activity, reduced stress reactivity, and diminished allostatic load.
A search of the literature between 1994 and 2009 through Pub
Med using the words ‘yoga’ and ‘epilepsy’ identified five controlled
studies in adults who had continued to have seizures despite treat-
ment with antiepileptic drugs [27,32–35]. All five studies reported
significant decreases in seizure frequency in groups treated with
yoga. In addition, one study documented concurrent decreases in
biological markers of stress: galvanic skin response, blood lactate,
and urinary vinyl mandelic acid [35,95]. In normal subjects, the
practice of Iyengar yoga is associated with increased PNS activity,
improved mood, decreased anxiety and increased thalamic GABA
levels, all of which could contribute to decreased seizure frequency
[60,75]. Thus reduction in stress, increased PNS activity and in-
creased brain GABA levels associated with yoga-based interven-
tions would all contribute to improved seizure control.
Yoga treatment for depression
Controlled studies have found yoga-based interventions to be
effective in treating depression ranging from mild depressive
symptoms to major depressive disorder (MDD) . The yoga-
based interventions have included Sudarshan Kriya Yoga (empha-
sizing breath practices), Iyengar Yoga, and Resonance Breathing
[54,96,97]. Iyengar yoga has been shown to decreased depressive
symptoms in subjects with depression . Iyengar yoga is associ-
ated with increased HRV, supporting the hypothesis that yoga
breathing and postures work in part by increasing PNS tone .
The success of yoga-based therapies in alleviating depressive
symptoms is consistent with the proposed neurophysiological
mechanisms: yoga breathing induces increased parasympathetic
tone which increases GABAergic activity associated with improved
mood and anxiety reduction.
Fig. 3. Stress related imbalance corrected by yoga-based practices.
C.C. Streeter et al./Medical Hypotheses 78 (2012) 571–579
Yoga treatment for stress, anxiety disorders, and PTSD
Controlled studies have demonstrated that yoga practices de-
creased symptoms in PSTD, Obsessive Compulsive Disorder, Gener-
alized Anxiety Disorder, Panic Disorder, and anxiety after natural
disasters [29,30,98–100]. For example, a controlled study of 183
survivors of the 2004 Southeast Asia tsunami found that within
one week, an eight-hour yoga breathing intervention resulted in
a 60% decline in scores on the Post-traumatic Stress Disorders
Checklist (PCL-17) and a 90% drop in scores on the Beck Depression
Inventory (BDI). These improvements were sustained at 6-week
and 6-month follow-up. In comparison, no significant change oc-
curred in PCL-17 or BDI scores between baseline and 6-weeks in
the wait-list control group . These findings indicate that co-
morbid symptoms of depression and PTSD were decreased by a
yoga breath-based intervention. Yoga practices also reduce stress
and anxiety in subjects without a psychiatric diagnosis, suggesting
that the beneficial effects of yoga are generalizable to larger popu-
lations [101,102]. Evidence that yoga-responsive anxiety disorders,
including PTSD, Generalized Anxiety Disorder, and Panic Disorder,
have low HRV and low GABA activity is in accord with the theory
that imbalances in the ANS and GABA systems constitute an allo-
static load that can be reduced by yoga-based therapies [19–
Correcting ANS and GABA abnormalities decreases PTSD symp-
toms. The interactions of the prefrontal cortex (PFC), hippocampus
and amygdala in conjunction with inputs from the ANS and GABA
system provide a network through which yoga-based practices
may decrease symptoms. In response to stressful tests, for exam-
ple, subjects with PTSD show a pattern of decreased PFC activation
and increased amygdala activation consistent with failure of the
PFC to inhibit the amygdala . In response to emotionally laden
cues, PFC activity decreases in PTSD subjects, a group known to
have reduced PNS activity, as opposed to the increased PFC activa-
tion seen in subjects with higher PNS activity . Compared to
subjects with low HRV, subjects with high HRV had faster reaction
time and fewer errors on a continuous performance task that re-
quires the support of the PFC . In addition, subjects with high
HRV had lower cortisol levels after a cognitive test compared to
subjects with low HRV, implying that high HRV is associated with
a decrease in perceived stress . To summarize, subjects with
PTSD have low HRV, decreased activation of the prefrontal cortex,
and increased activation of the amygdala.
The PFC exerts tonic inhibitory control over the amygdala via
GABA projections . Under conditions of uncertainty and threat,
the PFC can become hypoactive  leading to a failure to inhibit
overactivity of the amygdala with emergence of PTSD symptoms
such as hyperarousal and re-experiencing. This could represent a
neural correlate of the failure of extinction of fear reactions over
time as seen in PTSD . PFC activation associated with increased
PNS activity could improve inhibitory control over the amygdala
via PFC GABA projections, decreasing amygdala overactivity and
reducing PTSD symptoms.
The insular cortex also sends inhibitory GABAergic projections
to the Central Extended Amygdala (CEA) . From the CEA, GAB-
Aergic neurons project to the PBN and dorsal vagal complex .
The insular cortex is located deep in the Sylvian fissure between
the temporal and frontal lobes. Sensory information from the envi-
ronment and interoceptive information about the internal homeo-
static condition of the body are conveyed by the PNS via the NTS to
the insular cortex where, according to Craig’s neuroanatomical
theory, a map of the internal state of the body is maintained
. While activation of the amygdala is necessary for energy
mobilization, over activation of the amygdala as seen in PTSD re-
flects allostatic load associated with the hypervigilant condition
(excessarousal) .According to our proposedtheory,
restoration of strong tonic GABAergic inhibition of the amygdala
would result in decreased output from the CEA to the hypothala-
mus and brainstem nuclei, reducing symptoms of hyperarousal,
over reactivity, and re-experiencing in PTSD . Psychological
states such as anxiety, depression, and PTSD, associated with PFC
hypoactivity and lack of inhibitory control, are characterized by
poor habituation to novel neutral stimuli, pre-attentive bias for
threat information, deficits in working memory and executive
function, and poor affective information processing and regulation
. The presence of GABA neurons in the thalamus, insular cortex,
amygdala, and hippocampus as well as GABA projections from
both the insular cortex and the PFC to the amygdala completes
the pathways that would constitute an anatomical substrate for
the effects of ANS balance and imbalance on emotion regulation
and cognitive function (see Fig. 1).
Empirical data-yoga treatment for chronic pain and depression
Chronic pain is associated with ANS abnormalities . In hu-
mans, the antinociceptive effect of VNS may rely on central inhibi-
tion rather than alterations of peripheral nociceptive mechanisms
. The NTS sends projections to the periacqueductal grey
(PAG), a pontine structure containing GABA neurons which is
important in behavioral responses to threat, stress and pain
. Stimulation of the PAG increases HRV and decreases pain
. GABA receptors in the thalamus are implicated in pain con-
trol . Following a 60-min yoga posture session, a 34% increase
in thalamic GABA levels has been shown in experienced yoga prac-
titioners and a 15% increase in novices with 12 weeks of yoga pos-
ture training [75,118]. Back pain and depression are frequently
comorbid and have both been successfully treated with yoga-based
interventions in randomized controlled studies [31,119,120]. Two
studies are discussed in detail as a foundation for empirical data
not presented elsewhere on the effects of a 12-week yoga interven-
tion in two depression subjects with chronic low back pain.
Yoga and walking (YW) study
Normal subjects with no prior yoga experience were random-
ized to either a 12-week Iyengar yoga intervention (n = 19) or a
12-week metabolically matched walking intervention (n = 15).
Both groups were scanned by magnetic resonance spectroscopy
(MRS) before (Scan 1) and after (Scan 2) the 12-week interventions.
After completing Scan 2, the yoga subjects performed a 60-min
yoga session followed immediately by Scan 3. After completing
Scan 2, the walking group subjects performed a 60-min walking
session followed immediately by Scan 3. In both groups of normal
subjects there were no significant increases in tonic GABA levels
(Scan 2–Scan 1) over the 12-week study. However, there was an
acute increase in thalamic GABA levels immediately after the 60-
min yoga session (Scan 3–Scan 2). These increases in thalamic
GABA levels in the yoga group were positively correlated with im-
proved mood and decreased anxiety. There were no significant
changes in GABA levels in the walking group. The yoga group also
showed a significant improvement in mood and decreased anxiety
during the 12-week intervention compared to the walking group.
Such observations support the hypothesis that part of the effect
of yoga is vagal afferent activation by slower breath rates often
used during yoga posture techniques, but not during walking.
Chronic low back pain (CLBP) study
In a randomized controlled trial, a 12-week Hatha yoga inter-
vention designed for treatment of chronic low back pain was com-
pared to usual care . Subjects in the yoga intervention showed
significantly greater reduction in pain scores compared to subjects
C.C. Streeter et al./Medical Hypotheses 78 (2012) 571–579
receiving standard care. Two subjects with comorbid chronic low
back pain and MDD were recruited from the CLBP Study so that
GABA levels before and after the 12-week Hatha yoga intervention
could be obtained using the same acquisition sequence used in the
Iyengar yoga is a branch of Hatha yoga. Review of the two
manualized 12-week interventions, Iyengar yoga from the YW
study and Hatha yoga from the LBP study showed that the two
12-week interventions were comparable, thus allowing compari-
son of MRS data from subjects from the LBP study with the normal
subjects from the YW study [75,121]. The depression module of the
Patient Health Questionnaire 9 (PHQ-9) was used to measure
depressive symptoms . PHQ-9 scores P 10 have 88% specific-
ity and 88% sensitivity for the diagnosis of MDD . Subjects had
PHQ-9 scores of 22 (severe depression) and 20 (moderately severe
depression) at the beginning of the yoga intervention and scores of
7 (mild depression) and 4 (not depressed enough to be considered
MDD) respectively at the end of the study. The depressed subjects
with chronic low back pain had mean thalamic GABA levels of
0.039 ± 0.004 GABA/Creatine ratios (GABA levels) before the 12-
week yoga intervention (Scan 1) and mean GABA levels of
0.049 ± 0.010 after the intervention (Scan 2) for a change of
0.014 ± 0.006. The normal subjects had mean GABA levels of
0.065 ± 0.021 for Scan 1, and 0.061 ± 0.021 for Scan 2, for a change
of ?0.004 ± 0.017 (see Fig. 2). There were no significant changes in
tonic GABA levels over the 12-week intervention in the normal
subjects (t = ?1.01, df = 18, p = 0.33), presumably because they
had been screened to not to have any disorders associated with
low GABA levels such as depression, anxiety or chronic pain. In
contrast the chronic low back pain group showed a greater in-
crease in GABA levels over the course of the study. Although the
small number of low back subjects (n = 2) precludes statistical
analysis, their lower GABA levels at baseline increased after the
yoga intervention towards the level seen in the normal group. Both
subjects had been unresponsive to pharmacologic treatments with
agents known to increase the activity of the GABA system. Subject
#1 was taking duloxetine, atomoxetine, clonazepam and eszopi-
clone; Subject #2 was taking fluoxetine. Medications were taken
at the same time prior to each scan to reduce any acute effect of
the medications on GABA levels. The results from these two sub-
jects are consistent with the proposed theory that predicts (1)
the lower GABA levels found in subjects with depression or low
back pain, (2) an increase in GABA levels towards those of normal
subjects after a 12-week yoga intervention, (3) improved mood in
association with increased GABA levels, (4) subjects remained
symptomatic with low GABA levels until they received the yoga
intervention that presumably corrected their PNS imbalance, after
which GABA levels increased and depressive symptoms decreased,
(5) the comorbidity frequently seen in depression and chronic pain
can be explained by imbalances in the PNS and GABA systems seen
in both disorders.
The autonomic nervous system plays a central role in the re-
sponse to stress. The imbalances that develop under conditions
of stress can be traced to decreased PNS activity and increased
SNS activity. Stress exacerbates symptoms in disorders associated
with low GABA activity, such as epilepsy, depression, PTSD, and
chronic pain. These stress exacerbated disorders are marked by
PNS underactivity as indicated by low HRV, increased HPA Axis
activity as indicated by increased cortisol, and reduced GABAergic
activity in the CNS (see Fig. 3).
Stressand its consequence,
symptoms of epilepsy, depression, PTSD, chronic pain and other
disorders that are impacted by stress reactive systems. The thera-
peutic effects of yoga can be understood in part through its direct
effects on the autonomic nervous system and indirect effects on
the GABA system. Evidence suggests that interventions such as
VNS and yoga, which increase PNS and GABA activity, may be
effective in treatment resistant subjects who failed to respond to
pharmacologic agents that increase activity in the GABA system
. Accordingly in some cases, correction of ANS imbalance
may be a necessary factor that allows for the improvement of
GABA function, and possibly in other systems as well.
The components of the proposed theory will need further test-
ing and refinement using controlled studies, larger sample sizes,
brain imaging, and other emerging technologies. The model pre-
sented may be of heuristic value as a framework for the integration
of new research information about the pathophysiology and inno-
vative treatment of conditions with significant morbidity and
Summary and future implications
An explanatory framework is presented that attributes the ben-
efits of yoga to the reduction of allostatic load in frequently comor-
bid conditions. Neurophysiological, neuroanatomical, and clinical
evidence converge in support of the proposed theory of shared
pathogenesis and responsiveness to treatments, such as yoga, that
stimulate an under active parasympathetic nervous system and in-
crease the inhibitory action of a hypoactive GABA system in brain
pathways and structures that are critical for threat perception,
emotion regulation, and stress reactivity. Furthermore, yoga prac-
tices can be used as non-invasive probes to explore dynamically
the body’s stress response and regulatory systems. The insights
gained from such studies could be utilized to develop a lexicon
of specific mind–body practices for prevention and treatment of
a wide range of neuropsychiatric and stress-related medical
Conflict of interest
C.C. Streeter reports no conflicts of interest. P.L. Gerbarg reports
no conflicts of interest. D.A Ciraulo reports no conflicts of interest.
R.B. Saper reports no conflicts. R.P. Brown reports a possible con-
flict with a pending patent, Confirmation No. 9891, using 7-keto
DHEA for the treatment of Post Traumatic Stress Disorder.
This paper was supported, in part, by Grants from the National
Institute of Complementary and Alternative Medicine (R21
AT004015 to C.C.S., and K07 AT002915 to R.B.S.), the National Insti-
tute of Drug Abuse (DA50038 to D.A.C.), the National Institute on
Alcohol Abuse and Alcoholism (K23AA13149 to C.C.S., and
AA013727 to D.A.C), the National Center for Research Resources
(M01RR0533) and the Gennaro Acampora Charity Trust to the Divi-
sion of Psychiatry, Boston Medical Center. We would like to thank
Stephen W. Porges, Ph.D. for his assistance with the development
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