Yoga has been gaining popularity ever since the declaration of the International Day of Yoga by the United Nations (UN) in 2015. This declaration was preceded by a steep rise in yoga research through 2010 threefold in the next decade. PubMed annually recorded 640 articles from 2017–2021 against 180 earlier 2007–2011.
A search for the term yoga therapy, too, yielded a similar rise after 2010 though not as steep. The application value of yoga in health is the net benefit to the health sector. The recent COVID pandemic witnessed such effect of employing yoga in public health.[2,3]
Textbooks have come up for reference work illustrating yoga’s role in clinical medicine.[4-8] The National Medical Commission has also allowed an elective posting in Indian Systems of Medicine including Yoga during the internship (Notification number No. UGMEB/NMC/Rules & Regulations/2021/dated 18th November 2021; https://ncismindia.org/Ayush%20Module%20Internship%20Electives%20for%20MBBS.pdf.
Clinicians, however, continue to express the caution to remain objective and demand ‘evidence’ for the application of yoga for ‘therapy’. Thus, yoga has been put to test in clinical medicine to build evidence. There, however, are challenges, for example, blinding (as in double-blind) is one such challenge. There is also no ‘placebo’ that is appropriate in clinical yoga research and the other aspect is difficulty in ‘randomization’. People seeking help in traditional yoga centers/hospitals accept it with faith and may not think it needs research. Likewise, in modern hospitals, patients may not expect that yoga as a service exists and is under research. Despite these challenges, clinicians have explored yoga intervention in several disorders. The available data have been examined using meta-analysis when there are more studies. Psychiatric disorders treated with yoga have attracted research. Some examples include depression, schizophrenia, anxiety, obsessive–compulsive disorder (OCD), somatoform pain, addiction, mild cognitive impairment, and elderly and childhood disorders.
Depression is among the widely studied condition. In the meta-analysis, Cramer (2013) reported that yoga offers better benefits for depression as compared to treatment, as usual, relaxation, or aerobic exercise. In these analyzed studies, yoga was an add-on treatment. Yoga alone too produced significant benefits and was even comparable to standard treatment for depression. A similar finding was also earlier reported in a randomized controlled trial (RCT) comparing yoga along with imipramine and electro-convulsive therapy (ECT). ECT produced the best results. Both yoga and imipramine produced comparable improvements. In a more recent study, but not an RCT, yoga alone produced significant benefits in depression. One of the treatment guidelines (CANMAT 2016) has included yoga as an add-on treatment for depression.
A couple of meta-analyses examining yoga in anxiety disorders found positive effects albeit of small magnitude.[15,16] Treatment of post-traumatic stress disorder includes attention control and yoga. A meta-analysis demonstrated the superiority of yoga. The comparable benefit of yoga over no treatment was strong. The effect size was close to one, favoring yoga in that comparison. The yoga breathing technique as an intervention in the Tsunami disaster helped reduce PTSD symptoms. The therapeutic effects of yoga on OCD were examined in a case series and then subsequently in a randomized clinical trial (Unpublished PhD Thesis by Bhat, 2022). The study had 20 patients in the yoga group and 22 in the control. Yoga was an add-on intervention over ongoing drug treatment for 4 weeks. The addition of yoga produced a nearly 30% reduction in obsession symptom scores. The reduction in the group that did not receive yoga was marginal. The difference favored yoga addition in OCD. In earlier studies Shannahoff-Khalsa et al.[20,21] demonstrated the benefits of Kundalini yoga in OCD.
Schizophrenia outpatients on maintenance anti-psychotic medicines continue to have some residual negative symptoms. There are also associated functional and social cognition deficits in these patients. Independent studies have demonstrated the benefits of yoga over exercise or waitlisting. Yoga reduced negative symptoms, improved social cognition, and also improved social functioning.[22-27] One of the treatment guidelines (NICE) in 2014 included yoga as an add-on treatment in the management of psychosis.
Subjects undergoing detoxification for alcohol dependence in the wards were offered Sudarshan kriya with conventional treatment or the latter alone without yoga. The addition of yoga was significantly beneficial. More recently, yoga was provided to patients with opiate dependence. The patients obtained benefits with respect to improvement in the quality of life and reduction in withdrawal symptoms following yoga intervention.[30,31] Somatoform pain disorder is another condition where yoga has proven useful. Patients lose symptoms following yoga. Yoga has produced improvements in cognitive function in elderly subjects who have symptoms of mild cognitive impairment. This was a randomized trial comparing a waitlisted group. Similar benefits of yoga have been recorded in other measures when offered to elderly subjects.
In children with autism, adding yoga practices reduces symptoms. Yoga also reduced symptoms of attention deficit hyperactivity disorder (ADHD) in inpatients. However, this was not a comparison trial.
These studies are conducted on patients reaching treatment centers (except in the study with the elderly). Apart from these, yoga’s effects on several mental states such as memory, dysphoria, attention, and sleep have been documented in a healthy population. Clinicians, however, accept study results in clinical populations for application; even better, if that such effects can be documented from the inpatients.
Clinical trials versus case series
Case reports alone suggesting a therapeutic effect of an intervention can merely hint at a possibility of application.
Case series documenting the beneficial effects of an intervention in a diagnostic group would have a better weight.[19,38-40] Though the evidence may encourage others to use the intervention, the same will not get an ‘official’ sanction. Clinical trials strengthen the evidence for or against its use.
Clinical trials in yoga therapy
Although this oration is not the place to provide the details of the trial methods; it is clear that barring double-blind trials, other methods have been used in yoga research, albeit with challenges.
Randomized versus non-randomized
Yoga, by way of its long-term public use, has not been questioned. The naïve public may even be surprised that it is now being ‘tested’ for its efficacy in a given condition. Those approaching yoga centers for expecting benefits from yoga for their condition may not be clinically diagnosable. In contrast, patients reaching modern medicine service centers may not expect competency in yoga therapy in these centers. At the same time, their preference will be for modern medicine. Randomization of patients/subjects to yoga or other group and informed consent are the challenges. The studies hence could be on self-selected subjects or pre-post comparison or crossover ones. The limitations of all three are known. The waitlisted control group may include a group that receives medicines alone or perhaps other usual treatments such as psychotherapies for mental disorders.
For stronger evidence, randomization should be into intervention and control groups. The latter include no treatment, treatment as usual, or similar non-medicine active interventions such as exercise. In modern hospitals, patients almost always receive conventional medicines (for example, anti-depressants, anti-psychotics, etc.). This brings in yet another factor. Intervention such as yoga is being tested as an add-on. Therefore, the clinical effects of modern medicine may mask any benefits of yoga intervention. In this background, a suitable placebo for yoga is much awaited. The nearest has been exercise though this too has substantial benefits, even biological.
In psychiatric practice (so also in other conditions) there is a need to blind the treatment in RCTs. Blinding is also needed to avoid rating bias from the clinician. This has posed a serious challenge. To blind the patient from the intervention, one needs to have a “similar-looking intervention that is expected not to have therapeutic properties. Such interventions shall also have other ethical concerns. The best alternative is to blind the rater who has to consciously avoid referring to the treatment and also the care that the patient has to take not to divulge the intervention. Some of these challenges have been recognized in clinical trials of yoga with psychiatric patients.
BIOMARKERS OF YOGA
To overcome these challenges and generate objective and compelling evidence for yoga in psychiatric disorders, one can examine biomarkers that are specific to yoga and even better, markers relevant to psychiatric disorders.
Are there specific biomarkers for each yoga procedure? For that matter, this is investigated poorly. This is further complicated by the fact that specific biomarkers (that can be altered) in psychiatric disorders are not available. The research into biological markers in yoga has elucidated changes in healthy subjects. In such yoga interventions, the researchers used a module that had different yoga components such as Asana (posture), pranayama, and meditation (Dhyana). Isolating the effects of each of these is difficult. One attempt has been made in the past. In a yoga protocol called Sudarshan Kriya Yoga, the investigators dropped one of the components for the ‘control’ group. There was a non-significant loss of benefit by a such deletion in depressed patients. More such work is needed as no biomarker was examined in this study.
Among the different biomarker effects of yoga in healthy subjects are those observed in the brain. Neuroprotection by yoga is evident in the findings of cross-sectional studies[42-44] that examined a population that had regularly practiced yoga for several years and compared this group with those that had not. Researchers measured the volume of gray matter in the brain. Age-dependent loss of gray matter was seen in the group that had not practiced yoga. In chronic yoga practitioners, such gray matter loss was not detected. This suggests that regular yoga practice ‘protected’ subjects from neuro-senescence. Similar findings have been shown in long-term meditators. Different mechanisms have been implicated in neuroprotection from yoga. Lowered oxidative stress and lowering of the levels of stress-hormone cortisol are examples. It is of interest to note this latter mechanism of yoga bears relevance to depression and some cognitive disorders (including dementias). Similar biomarkers that may be relevant to other psychiatric disorders merit attention. The remaining review/oration relates to demonstrating such relevant neurobiological markers of yoga in psychiatric disorders. For this purpose, two disorders are chosen in which the yoga benefits have been demonstrated with a strength that demanded the inclusion of yoga in some treatment guidelines. Depression and schizophrenia are the psychiatric conditions that benefit from yoga intervention as presented earlier in this oration. Biomarker studies that relate to these conditions are described below.
Neurology of depression
Limbic hyperactivity and frontal cortex hypoactivity (perhaps casual/reciprocal) are associated with depression. This has been the basis of deep brain stimulation (DBS) of a limbic structure to deactivate the region and produce therapeutic benefit thereof. DBS is a treatment (though invasive) limited to depressive illness when the latter fails to respond to conventional treatments, including ECT.
Limbic hyperactivity may also be caused by lowered brain GABA (gamma-aminobutyric acid), an inhibitory transmitter. Lowered GABA levels have been demonstrated in individuals with depressive disorders. The limbic hyperactivity in depression is also associated with dis-inhibition of the hypothalamic–pituitary–adrenal (HPA) axis as demonstrated by elevations of cortisol in these patients. This is also associated with resistance to suppression by exogenous dexamethasone. Brain-derived neurotrophic factor (BDNF) is low in depression, perhaps as a consequence of elevated cortisol levels. BDNF levels are also mooted to be state-dependent and potentially diagnostic in depression. The net effect of these biological changes in depression is the associated loss of gray matter in select regions of the brain in those who have chronic depression.
Biomarkers of yoga in depression
The neuroprotective effects of yoga may also have these pathways when used as a treatment for depression. We have a lead, though not from research on depression. One of the yoga practices, OM chanting, was associated with limbic deactivation in healthy subjects. The authors demonstrated that OM chanting in comparison to a non-OM expiratory hiss (Sssss), produced deactivation in certain brain structures including the limbic system. OM changing is a part of most of the yoga modules used. Yoga is associated with elevations in brain levels of GABA as demonstrated using magnetic resonance spectroscopy. The authors demonstrated similar GABA elevation in depressed subjects treated with yoga. It remains to be established if this GABA elevation following yoga is an associated/result of limbic deactivation in these interventions. More recently, using a physiological model, Jakhar et al., observed lower functional activity of GABA in depression. The authors also examined the change following yoga intervention. The comparison group had walking as an intervention. Modern medicine treatment in these two groups was continued. Yoga intervention, albeit of a very short duration, produced significant elevations in GABA function in these patients. The neurophysiological marker was the cortical silent period (CSP) as measured by a transcranial magnetic pulse stimulation as a probe. Following the intervention, the Yoga group had a longer CSP suggesting the ‘normalizing’ of the GABA aberration seen in depression.
A similar ‘normalizing’ effect of yoga on the HPA disinhibition seen in depression is documented in subjects who were undergoing treatment for alcohol withdrawal syndrome. Inpatients were randomized to receive sudarshana kriya yoga (SKY) or were waitlisted. Cortisol levels dropped following 2 weeks of treatment in the wards. The cortisol-lowering effect was correlated with reductions in depression scores.[12,29] More recently, this has been replicated in outpatient subjects with depressive illness. Over 65% of depressed subjects lost cortisol levels following yoga, whether given as monotherapy or with concurrent antidepressant medicines. Again, the cortisol lowering correlated with the lowering of depression scores. We also demonstrated that in subjects with depressive illness, the BDNF levels were lower than in healthy control subjects. Treatment with yoga not only produced clinical improvement but also resulted in a significant elevation in BDNF whether the patient received concurrent medicines or not. Interestingly, the BDNF elevations occurred in those who lost cortisol levels and vice versa. It is likely that higher levels of cortisol prevented brain repair through the attenuation of the BDNF mechanism. It remains to be prospectively examined if continued yoga practice in depressed subjects prevents grey matter loss in chronically ill subjects. However, 6 months of yoga practice in elderly subjects (mean age 70 years) led to an increase in gray matter in the hippocampus, a region that is most vulnerable to age-dependent gray matter loss. Together, the findings of these biomarker studies of yoga in depression are encouraging. Yoga has the potential not just to produce clinical benefits, but also ‘undo’ the biological substrates that explain the psychiatric disorder or biological correction.
YOGA IN SCHIZOPHRENIA
The other disorder that benefits strongly from yoga is schizophrenia. The condition is characterized by a ‘disconnect’ between mental operations. The thought and effect are desynchronized. The perceptions and the thoughts/affect too are desynchronized. No wonder the term schizophrenia symbolizes the ‘schism’ in these psychic operations resulting in a grossly apparent behavior that gives its clinical name. The person so affected remains ‘disconnected’ from his/her social milieu. This adds to the disability. Social cognition is also deficient in schizophrenia. Social, cognition is required to establish this ‘connect’ between social beings. Yoga derives its name from the root word yuj which means to connect; a connection between the personal and cosmic consciousness in a spiritual context. Yoga is a lifestyle to achieve this connection. It is hence intuitive to consider that yoga would in its early stages help ‘connect’ neighboring consciousness as a forerunner to the final spiritual connect. Hence, one could expect yoga to induce the feeling of ‘connectedness’ between individuals.
The emergence of this connectedness feeling has been implicated in anti-depressant effects. A biological substrate for this connected feeling is the hormone oxytocin also called the cuddling hormone. The effects of this hormone have been exploited in obtaining benefits in conditions characterized by an emotional or social disconnect. Examples include schizophrenia and autism, in both yoga has demonstrated benefits.[23,35]
In schizophrenia, oxytocin nasal spray has been tried to improve social cognition and in turn, the functional outcome. In schizophrenia, blood levels of oxytocin were demonstrated to be lower than in healthy age-matched control subjects. Jayaram et al. demonstrated that yoga intervention in schizophrenia produced elevations in the level of oxytocin. These patients also had improvements in social cognition. Yoga can hence be considered ‘autogenous’ oxytocin therapy against the ‘exogenous’ (nasal spray) oxytocin therapy.
Schizophrenia individuals have also disconnections in brain networks. This is studied by resting-state functional magnetic resonance imaging. The default mode network has poor coherence in schizophrenia. In a recent randomized comparison of yoga intervention for outpatients with schizophrenia on maintenance treatment with anti-psychotics, patients who received yoga obtained significant reductions in negative symptoms. The coherence of the default mode network significantly increased in the yoga group as compared to the coherence that existed before starting the treatment (Varambally et al. personal communication-unpublished data). These neurophysiological ‘corrections’ of connectedness may have a bearing on experimental and behavioral connectedness that account for the clinical benefits of yoga in schizophrenia.
This evidence based on the biology of yoga ‘undoing’ a pathophysiological substrate for psychiatric disorders as illustrated with patients of depression and schizophrenia is compelling. This should encourage clinicians to recommend yoga in their practice. However, such a change also demands other questions. Is there a generic yoga protocol that is independent of other copyright concerns, and independent of faith-based practices? Are there standardized protocols for yoga for specific disorders? Are there any precautions or side effects that one should be concerned about when prescribing yoga to psychiatric patients? Many of these questions have been addressed in recent publications.[4,69] Standardized yoga modules for different conditions such as depression, schizophrenia, anxiety, OCD, ADHD, and opiate dependence are available as free weblinks (www.nimhansyoga.in). One of these has also been tested as a protocol on a telemedicine platform. This tele yoga has been investigated for its effectiveness.[71,72] It is time hence a yoga therapist becomes an integral part of the psychiatrists’ team along with clinical psychologists and social workers.
The future work should include bringing a regulatory body to oversee the formal training and accord ‘registration’ for the yoga therapist in different specialty areas such as psychiatry, cardiology, and endocrinology. This can set the stage for insurance coverage of yoga therapy/intervention in psychiatric diseases. There is also a need to build the human resource to take this load of clinical services. There is a need to generate interest among allopathic physicians in yoga. Legitimizing exposure to Ayush systems (including yoga during an elective internship posting) by the National Medical Commission (weblink) is a promising beginning. A recent news item about a national institute planning to bring a curriculum in yoga (and Ayurveda) into the MBBS education is another encouraging move (https://medicaldialogues.in/news/education/pgi-chandigarh-will-include-yoga -ayurveda-and-traditional-medicine-in-its-upcoming-mbbs -curriculum-97631). Medical practice should be inclusive and integrated to complement each other for best benefits to the needy. Yet another national institute has developed an Integrative Medicine Department (NIMHANS, Bengaluru). The department’s objective is to develop such integrated evidence-based treatment options and training of clinicians to create evidence-based scientific models of integrative medicine, especially in the field of psychiatry and neurology.
In summary, the evidence base for integrating yoga in treating psychiatric disorders is increasing from different angles. This has paved the way for safe and effective use of yoga in current psychiatric practice. There is a need to have a yoga therapist as part of a multi-disciplinary team with psychiatrists.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
I thank the NIMHANS administration for extending all support for these activities in the yoga center. Sri Ravishankar Guruji and Dr. HR Nagendraji initiated me into yoga academics. MDNIY and CCRYN, Ministry of AYUSH were highly supportive. The team at the Integrative Medicine Department, NIMHANS, Bengaluru, led by Prof. Varambally deserves appreciation. The manuscript has been edited by Dr. Hemant Bhargav.
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