Asian Journal of Psychiatry 62 (2021) 102731

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Asian Journal of Psychiatry

journal homepage: www.elsevier.com/locate/ajp

Yoga therapy for social cognition in schizophrenia: An experimental

medicine-based randomized controlled trial
Ramajayam Govindaraj a, *, 1, Shalini S. Naik b, 1, Urvakhsh M. Mehta b, Manjunath Sharma c,
Shivarama Varambally d, B.N. Gangadhar b
a
Centre for Consciousness Studies, Department of Neurophysiology, National Institute of Mental Health & Neurosciences, Bengaluru, India
b
Department of Psychiatry, National Institute of Mental Health & Neurosciences, Bengaluru, India
c
Anvesana Research Laboratory, S-VYASA University, Bengaluru, India
d
Department of Integrative Medicine, National Institute of Mental Health & Neurosciences, Bengaluru, India

A R T I C L E I N F O A B S T R A C T

Keywords: Negative symptoms and cognitive deficits are difficult-to-treat symptoms of schizophrenia. In this single blind
Yoga randomized controlled study, we compared change in social cognitive performance in persons with Schizo­
Schizophrenia phrenia (PWS) (as per DSM-5), after 6 weeks of yoga intervention with a waitlist control group. We also
Social cognition
examined changes in putative Mirror Neuron System (MNS) activity measured by Transcranial Magnetic Stim­
Negative symptoms
Social disability
ulation (TMS) in a subset of sample (n = 30). 51 PWS stabilized on antipsychotic medication for at least 6 weeks,
were assigned to add-on yoga therapy (YT) (n = 26) or waitlist (WL) (n = 25). Subjects in the YT group received
add-on yoga therapy (20 sessions in 6 weeks). Both the groups continued their standard treatment and were
assessed at baseline and after 6 weeks for social cognition, clinical symptoms and social disability. RM-ANOVA
showed significant interaction between time and group for social cognition composite score (SCCS) (F = 42.09
[1,44], P < 0.001); negative symptoms (SANS) (F = 74.91 [1,45], P < 0.001); positive symptoms (SAPS) (F =
16.05 [1,45], P < 0.001) and social disability (GSDS) (F = 29.91 [1,46], P < 0.001). MNS activity had increased
after 6 weeks in both groups but not of statistical significance. This study demonstrates that 6 weeks of add-on
yoga therapy could improve social cognition in PWS compared to waitlist control subjects. However, the change
in social cognition was not associated with a change in the putative MNS-activity. It necessiatates further studies
to investigate the mechanistic processes of yoga and replicate these observations in a larger sample.

1. Introduction defined as mental operations that underlie social interactions(Brothers,

Schizophrenia is characterized by three important symptom clusters
namely positive, negative & cognitive symptoms. Persons with schizo­
phrenia (PWS) often seek treatment for positive and negative symptoms.
However, cognitive deficits are much earlier to occur and has more
debilitating effects on functional outcome. Broadly cognitive symptoms
could be classified as neurocognition or social cognition deficits. Neu­
rocognition (non-social) and social cognition are two related yet distinct
latent dimensions of cognitive symptoms in schizophrenia (Mehta et al.,
2013), both of which have a substantial inter-dependent impact on
real-world functional outcomes (Fett et al., 2011). Social cognition is
1990). Most frequently studied aspects of social cognition in schizo­
phrenia are Theory of Mind (ToM), Emotion processing (EP), Social
perception (SP), Social knowledge, and Attribution Style (AS) (Couture
et al., 2006; Penn et al., 2008). Except for the positive symptoms, there
are no effective treatments available for the negative and cognitive
symptoms including social cognition deficit (Buckley and Stahl, 2007) In
addition, the existing treatments are not free of side effects; some
causing extrapyramidal side effects and others causing metabolic side
effects.(Abbott, 2010)
Psychosocial interventions are available targeting a few or most of
the domains of social cognition with or without neurocognition training.

* Corresponding author at: Scientist-C, Centre for Consciousness Studies, Department of Neurophysiology, National Institute of Mental Health and Neurosciences,
Hosur Road, Bengaluru, 560029, India.
E-mail addresses: ramji.zero@gmail.com (R. Govindaraj), drshalini.anji@gmail.com (S.S. Naik), urvakhsh@gmail.com (U.M. Mehta), nkmsharma@gmail.com
(M. Sharma), ssv.nimhans@gmail.com (S. Varambally), kalyanybg@yahoo.com (B.N. Gangadhar).
1
Equal contribution/Joint first authors.

https://doi.org/10.1016/j.ajp.2021.102731
Received 22 January 2021; Received in revised form 20 May 2021; Accepted 30 May 2021
Available online 1 June 2021
1876-2018/© 2021 Elsevier B.V. All rights reserved.
R. Govindaraj et al.
But the majority of them [for example, Cognitive Enhancement Therapy
(CET), Social Cognition Interaction Training (SCIT)] are highly
resource-intensive and their feasibility in developing countries is ques­
tionable. Moreover, they were developed keeping the western patient
population in mind and their cultural validity in other cultures is
questionable. In addition, the magnitude of benefits following such in­
terventions is variable (effect sizes range between 0.30–1.29) (Kurtz
et al., 2016), and their generalizability to improvements in functional
outcomes is minimally evaluated. Hence, there is a need to explore the
role of other complementary therapies like yoga, ayurveda, homeopa­
thy, and music therapy for an indigenous, integrated approach in
treating PWS. Among the complementary therapies, Yoga is unique in
following an integrated approach engaging body, breath & mind unlike
others.
In healthy adults and the elderly, yoga is found to be efficacious in
improving cognitive skills (Gothe and McAuley, 2015). As an add-on
treatment, yoga is more effective than physical exercise in reducing
the negative symptoms in PWS (Duraiswamy et al., 2007; Varambally
et al., 2012). It also improves the quality of life in PWS (Cramer et al.,
2013; NICE, 2014), More recent studies have examined the therapeutic
effects of yoga on neurocognition and reported cognitive gains in PWS
(Bhatia et al., 2017). Interestingly two randomized controlled trials
(RCT) have demonstrated improvement in Emotion Processing(EP)- an
important domain of social cognition (Behere et al., 2011; Jayaram
et al., 2013). One of these studies had also reported enhanced plasma
oxytocin in PWS following yoga intervention (Jayaram et al., 2013). In a
recent double-blind RCT, intranasal administration of oxytocin has been
shown to increase the activity of putative Mirror Neuron System (MNS)
in social contexts (Festante et al., 2020). Imitation and being imitated
are also associated with an increase in oxytocin (Delaveau et al., 2015).
This principle of practicing imitation & being imitated are integrated
into yoga training during group supervision. Recently, Insel proposed
investigating the biological mechanisms along with the clinical efficacy
is imperative. (Insel, 2015). Hence our study adopted the experimental
medicine-based approach for simultaneous investigation of the effect of
add-on yoga therapy on social cognition and the underlying putative
biological mechanism in PWS. To the best of our knowledge, there is no
study that has examined the putative biological mediators of therapeutic
gains following yoga practice.
In this study, we aimed to
a) Compare changes in comprehensive measurements of social cogni­
tion [encompassing theory of mind (ToM), emotion processing (EP),
social perception (SP), attribution style (AS)] in PWS assigned to
add-on yoga therapy (YT) or waitlist (WL) groups.
b) Examine changes in putative MNS activity measured by Transcranial
Magnetic Stimulation (TMS) between YT and WL groups.
We hypothesized that the practice of 20 sessions of yoga in six weeks
would improve social cognition composite score in PWS. Our secondary
hypothesis was MNS activity would also increase after 20 supervised
yoga therapy sessions in PWS.
2. Methods
2.1. Study participants
We conducted an RCT with PWS (N = 51) at a tertiary care neuro­
psychiatry hospital in south India in collaboration with a yoga univer­
sity. Both inpatients (n = 11) and outpatients (n = 40) seeking treatment
at the hospital were diagnosed by a qualified psychiatrist as per DSM-5
(American Psychiatric Association, 2013) guidelines and confirmed with
Mini-International Neuropsychiatric Interview (M.I.N.I.) (Sheehan
et al., 1998). Eligible and willing subjects were recruited after obtaining
written informed consent. Males & female patients in the age group of
18–45 years having a clinical global impression-severity (CGI-S) (Guy,
2
Asian Journal of Psychiatry 62 (2021) 102731
2000) score of 3 or more, stabilized on antipsychotic medication for at
least 6 weeks. Subjects with features suggestive of risk of harm to self or
others, requiring electroconvulsive therapy (ECT) or received ECT in the
last three months, co-morbid substance dependence in the last six
months or substance abuse in the last one month (except nicotine), a
significant neurological disorder (like seizure), or lifetime history of
significant head injury, regular practice of yoga in the last six months,
pregnancy or postpartum were excluded. The data was collected from
3rd March 2016 to 30th April 2019.
The authors assert that all procedures contributing to this work
comply with the ethical standards of the relevant national and institu­
tional committees on human experimentation and with the Helsinki
Declaration of 1975, as revised in 2008. All procedures involving pa­
tients were and approved by the Institute Ethics Committee (RES/IEC-
SVYASA/53/2015). All subjects were recruited with written informed
consent.
The study was registered with the Clinical Trials Registry-India
(CTRI/2017/09/009738) and is available at http://ctri.nic.in/Clinicalt
rials/advsearch.php
2.2. Sample size calculation
The sample size was calculated based on the effect size (d = 1.1) for
the Facial Emotion Recognition task, from a previous study (Jayaram
et al., 2013). The sample size required to detect a significant difference
in the variable of interest with a power of 0.90, allowing for 5% type I
error, was 38 (19 in each arm). Considering the drop out of 16 % in
previous studies, the sample size was rounded to 50 (25 in each arm).
2.3. Randomization
After a psychiatry resident enrolled the subjects, random assignment
of eligible and consenting subjects to Yoga Therapy Group (YT) or
Waitlist Control (WL) was done by the research scholar with the
Sequentially Numbered Opaque Sealed Envelope (SNOSE) method
ensuring allotment concealment with 1:1 ratio in the groups.Simple
randomization was used with computer-generated random numbers for
treatment assignment. Random numbers were generated by a scientific
officer who was not involved in the assessment or recruitment of the
subjects.
2.4. Intervention
Validated Yoga module (Govindaraj et al., 2016) was administered
to the Yoga group for 60 min, 4–5 sessions per week, with a total of 20
sessions to be completed within 6 weeks. This yoga module, the duration
and total number of yoga sessions in our study are the same as the
previous modules which have shown improvement in Emotion Pro­
cessing & serum oxytocin levels (Behere et al., 2011; Jayaram et al.,
2013) except for two practices that were deleted/modified following the
validation process. Most of the yoga sessions were individual sessions (a
maximum of 3 subjects were taught together in few sessions). The ma­
jority of the subjects finished 20 sessions in 6 weeks. Few subjects
finished in 4 weeks. For details of the yoga intervention. (see supple­
mentary material 1)
Waitlist participants were offered Yoga after 6 weeks.
2.5. Assessments
A trained yoga therapist administered the yoga intervention to sub­
jects. A trained psychiatry resident, blind to the treatment allocation
completed the clinical assessments (positive symptoms, negative
symptoms, and social disability/functioning) and TMS experiment. A
non-blinded research scholar completed the social cognition assess­
ments, which were computer-based objective tests (less prone to bias).
Subjects were non-blinded as it is not possible to blind in yoga studies.
R. Govindaraj et al. Asian Journal of Psychiatry 62 (2021) 102731

However, the subjects were strictly instructed not to reveal their group As mentioned above, both SOCRATIS and TRENDS have been vali­
status to the assessors. dated in the Indian cultural setting. Their psychometric properties
All assessments were performed at baseline and at the end of 20 (content, concurrent and known-groups validity, internal consistency,
sessions of add-on Yoga therapy. All subjects underwent clinical and and external validity) have been found to be satisfactory. Each test,
social cognitive assessments whereas only a subset of them (n = 30) except attributional bias, provides an index of the respective test per­
underwent a TMS experiment. formance, which is equivalent to the score of an individual on the test
Details of the assessments are as follows (also see supplementary divided by the maximum score possible. We consider metaphor and
material 2): irony detection as 1 st and 2nd order ToM respectively. Faux pas
recognition is often described as a higher-order ToM ability31
2.5.1. Intake proforma
A structured proforma was used to collect the details of socio- 2.5.4. Scale for assessment of negative symptoms (SANS) & scale for
demographic and clinical variables including age-at-onset, type of assessment of positive symptoms (SAPS): (Andreasen, 1984a,1984b)
onset, and duration of illness The SANS is a 25-item scale designed to assess the negative symptom
complex in five domains including alogia, affective flattening, avolition-
2.5.2. Mini-International neuropsychiatric interview (M.I.N.I.) apathy, anhedonia-asociality, and attention. The SAPS is a 34-item scale
MINI is a short structured diagnostic interview for DSM-IV-TR and designed to assess positive symptoms of schizophrenia in four domains
ICD-10 psychiatric disorders. of hallucinations, delusions, bizarre behavior, and formal thought
disorder.
2.5.3. Social cognition rating tool in Indian setting (SOCRATIS) (Mehta
et al., 2011) 2.5.5. Groningen social disabilities schedule (GSDS-II)
SOCRATIS is a tool, which is validated, in the Indian socio-cultural The Groningen Social Disabilities Schedule (Wiersma et al., 1988),
context to assess social cognition in PWS. It assesses the theory of which is a semi-structured, culture-neutral interview, based on the WHO
mind (first-order, second-order, and faux pas), attribution styles (32- Disability Assessment Schedule-II was employed for assessment of
point questionnaire), and social perception [SoCueReTI -Social Cue socio-occupational functioning of patients. It measures the social and
Recognition Test-Indian setting]. functioning capacity of the patients based on eight different social roles.
Consistent with expert committee recommendations (Green et al.,
2008), we selected 4 out of the 5 recommended social cognition do­ 2.5.6. Clinical global impression (CGI)
mains, namely, Theory of Mind (ToM), emotion processing, social CGI-S (severity) was used at the baseline for assessing the severity of
perception, and attributional bias. ToM, social perception, and attribu­ the illness and CGI-I (Improvement) was used at the end of six weeks of
tional bias were assessed using the Social Cognition Rating Tools in intervention (Guy, 2000).
Indian Setting (SOCRATIS). Emotion processing was assessed using the
Tool for Recognition of Emotions in Neuropsychiatric DisorderS 2.5.7. Mirror neuron system activity (MNS) with TMS
(TRENDS) (Behere et al., 2008). Transcranial magnetic stimulation (TMS) is a neurophysiologic
To avoid the learning effect, each domain in SOCRATIS was divided
equally into two parts. One part was used at the baseline and the second
part was used at the end of 20 sessions of Yoga training. Each part Table 1
comprised of two first-order ToM, two second-order ToM, one Baseline comparison data.
metaphor-irony, and five faux-pas recognition story tasks, four social Variables YT(N = 26) WL(N = 25) t/χ2 P
perception videos, and 16 attributional style questions. Age in Years 33.62(7.22) 32.92(6.40) 0.6 0.55
*Sex ratio, M: F 15:11 19:06 1.18 0.27
2.5.3.1. Theory of mind. Story-based tasks were applied to test for ToM *Married: Single 8:18 10:15 0.15 0.69
Years of Education 12.54(3.14) 11.20(4.13) 1.31 0.19
(including metaphor & irony and faux pas). All the stories were modified Duration of illness 9.08(5.94) 7.58(4.48) 1.01 0.32
from the original tasks published elsewhere (Wimmer and Perner, 1983; CGI illness severity 4.62(0.85) 4.76(1.01) − 0.55 0.58
Perner and Wimmer, 1985; Stone et al., 1998; Drury et al., 1998). Antipsychotic dosage 518.27 434.0 1.11 0.27
(329.05) (191.33)
SCCS score 0.61(0.11) 0.64(0.12) − 1.10 0.27
2.5.3.2. Attributional bias. This was assessed using a 32-point ques­ Total SANS score 47.76(14.32) 43.56 1.03 0.31
tionnaire where subjects were required to make causal attributions for (14.72)
positive and negative social events, adapted from the Internal, Personal, Total SAPS score 29.00(12.87) 24.72 1.11 0.27
and Situational Attributions Questionnaire (Kinderman and Bentall, (14.52)
GSDS score 2.44(0.42) 2.34(0.45) 0.64 0.52
1996). −
Resting Motor threshold† 36.2(7.33) 36.3(6.51) − 0.037 0.971
SI1mV [% MSO]† 46.6(7.5) 48.9(6.1) − 0.836 0.412
2.5.3.3. Social perception. A set of 18 true/false questions were asked on MEP in mV [elicited by 0.45(0.3) 0.6(0.3) − 1.154 0.26
social (e.g., Ali asked many questions about the movie because he was SI1mV]†
MNS with SI1mV during NA† 22.5(102.1) 4.85(32.9) 0.572 0.93
trying to impress Sunil) and non-social cues (e.g., Harish and Lakshmi
MNS with SI1mV during CA† 35.37(91.92) 50.38 − 0.460 0.43
were looking over a book together) after showing the subjects four each (68.41)
of low and high emotion videos depicting a social interaction. This test *
Ratios; YT-Yoga Therapy; WL-Wait List; values in the cell represent mean &
was adapted from the social cue recognition test (Corrigan and Green,
within bracket is standard deviation. SCCS-Social Cognition Composite Score;
1993).
SANS-Scale for Assessing Negative Symptoms; SAPS-Scale for Assessing Positive
Symptoms; GSDS-Groningen Social Disability Scale; CGI-S- Clinical Global
2.5.3.4. Tool for recognition of emotions in neuropsychiatric Disorders Impression of illness. Severity; SI1 mV - Stimulus intensity to evoke MEP of 1-
(TRENDS). This is a tool validated for use in the Indian population mV; MSO – Maximal Stimulator output; MNS- Mirror neuron system activity;
(Behere et al., 2008), which captures the full range and nature of NA- Neutral action-observation paradigm; CA – Context based action-
emotional expressions akin to real-life situations and can be utilized for observation paradigm.
behavioral and functional imaging studies in Indian patients. It con­
siders variations of age and sex on emotional expressions.
†
Sample size of 17 in YT and 13 in WL.

3
R. Govindaraj et al. Asian Journal of Psychiatry 62 (2021) 102731

probe used to excite the underlying cerebral cortex non-invasively
(McClintock et al., 2011). When TMS is applied to the primary motor
cortex; it produces peripheral motor evoked potential (MEP) that are
recorded using electromyography from hand muscles.
Subjects were seated in a quiet room with their head 50 cm from the
presentation monitor. Localization of the left primary motor cortex
(PMC) was done by observing the maximum MEPs in the right first
dorsal interosseous (FDI) muscle. The scalp position of this site was
marked by using an ink marker. The lowest intensity required to elicit
MEPs of more than 50 μV peak-to-peak amplitude in at least 5 out of 10
successive trials, in resting target muscle determined as resting motor
threshold (RMT) (Wassermann et al., 2008). Stimulus intensity to evoke
MEP of 1-mV (SI1 mV) was defined as the minimum intensity, evoking
1-mV peak-to-peak amplitude in the resting, right FDI muscle in 5 out of
10 successive recordings (Wassermann et al., 2008). Cortical reactivity
was recorded in the right FDI muscle with a single-pulse MEP obtained
with stimulus intensity required to elicit 1-millivolt MEPs (SI1 mV)
delivered over the left PMC. Fourteen-MEP recordings, using SI1 mV
were elicited in a 5-second interval, while the subjects observed each of
requires the contraction of the FDI to abduct the index finger. iii.
Context-based action-observation paradigm (CA): In this condition,
subjects were asked to observe a video of the emotionally embedded
motor action that was developed in an earlier study (Bagewadi et al.,
2018). The delivery of the TMS pulses was timed to coincide with the
part of the video during which the mother is desperately, repeatedly,
and unsuccessfully trying to unlock the door. The sequence of displaying
these experimental observation paradigms to each subject was ran­
domized. In order to guarantee optimal attention allocation during the
TMS experiments, subjects were instructed to pay attention to all the
stimuli throughout the experiment. In addition, to further ensure
attention, a second experimenter monitored the subjects’ behavior
similar to measures taken by previous studies (Mehta et al., 2014).
TMS pulses were delivered using a MagPro R30 device, with
MagOption, (MagVenture, Faraum, Denmark). Motor evoked potentials
(MEP) were recorded in the right first dorsal interosseus (FDI) muscle
using a One-channel EMG amplifier mounted on the MagPro system.
Signal-4 Software (Cambridge Electronic Devices, Cambridge, UK) was
used to perform data acquisition and analysis.

Cortical reactivity at action observation - Cortical reactivity at rest ∗ 100

MNS-activity =
Cortical reactivity at rest

the following observation paradigms.
i. Static image observation paradigm (SI): The subjects were asked to
observe a still image of a hand and a lock displayed on the monitor. ii.
Neutral action-observation paradigm (NA): The subjects were asked to
observe a video, which depicts the experimenter’s hand, holding a key in
lateral pinch grip (grasping objects between the side of the index finger
and the thumb) to perform locking/unlocking actions. This action
2.5.7.1. Calculation of putative MNS-activity. The percentage change of
cortical reactivity (MEP or cortical inhibition) from the control condi­
tion to goal-directed action observation states formed a measure of
motor cortical facilitation or putative MNA. It was calculated using the
following formula, where cortical reactivity refers to MEP (in millivolts)
for single-pulse paradigm evoked by SI1mV:

Table 2
Pre-post intervention data.
YT(N=26) WL(N=25) F Statisticsa

Variables Baseline 6 weeks Baseline 6 weeks

Mean (SD) Mean (SD) Mean (SD) Mean (SD) F1 F2 F3

SCCS 0.61(0.11) 0.88 (0.11) 0.64(0.12) 0.63(0.11) 44.69*** 15.98*** 42.09***

ToM 0.57(0.19) 0.83(0.21) 0.62(0.21) 0.58(0.20) 10.25** 5.23* 15.62***
FPCI 0.40(0.24) 0.94(0.12) 0.38(0.23) 0.32(0.24) 39.25*** 40.52*** 57.55***
ER 0.62(0.14) 0.81(0.09) 0.63(0.14) 0.67(0.09) 26.90*** 6.38* 9.33**
SPI 0.86(0.12) 0.97(0.11) 0.96(0.13) 1.00(0.30) 7.54** 4.04 0.31
Total SANS 47.76(14.32) 22.20(9.86) 43.56(14.72) 41.95(15.03) 100.69*** 4.57* 74.91***
Total SAPS 29.00(12.87) 10.29(6.21) 24.72(14.52) 19.08(12.09) 58.66*** 0.45 16.05***
GSDS 2.44(0.42) 1.40(0.49) 2.34(0.45) 2.11(0.54) 69.85*** 6.76* 29.91***
Resting Motor threshold† 36.23(7.3) 35(6.83) 36.3(6.5) 36(7.2) 0.74 0.38 0.18
SI1mV [% MSO]† 46.6(7.5) 47.4(7.2) 49(6.1) 47.7(9.3) 0.33 0.22 0.58
MEP in mV [elicited by SI1mV]† 0.454(0.31) 0.548(0.4) 0.6(0.3) 0.533(0.3) 0.05 0.35 1.61
MNS SI1mV during NA† 22.54(102.12) 26.75(47.97) 4.85(32.94) 33.83(65.94) 0.64 0.08 0.36
MNS SI1mV during CA† 118.51(301.55) − 17.69(33.39) − 15.9(19.76) − 0.32(60.5) 1.31 1.34 2.07

YT-Yoga Therapy; WL-Wait List; SCCS-Social Cognition Composite Score; SANS-Scale for Assessing Negative Symptoms; ToM-Theory of Mind; FPCI-Faux Pas Com­
posite Index; ER-Emotion Recognition; SPI-Social Perception Index, SAPS-Scale for Assessing Positive Symptoms; GSDS-Groningen Social Disability Scale; SI1 mV -
Stimulus intensity to evoke MEP of 1-mV; MSO – Maximal Stimulator output; MNS- Mirror neuron system activity; NA- Neutral action-observation paradigm; CA –
Context based action-observation paradigm.
a
Two Way Repeated Measures ANOVA; F1- Time effect; F2-Group effect; F3-Group × Time interaction effect.

*
P < 0.05.

**
P < 0.01.

***
P < 0.001.

†
Sample size of 17 in YT and 13 in WL.

4
R. Govindaraj et al.
Fig. 1. Consort chart.
MNS-activity was calculated with SI 1mV for both Neutral Action
observation paradigm (NA) & Context based action-observation para­
digm (CA). Refer Tables 1 & 2.
2.6. Data extraction & analysis
Clinical and social cognition data collected in assessment forms were
screened for completeness and entered in an excel sheet. TMS data was
extracted using signal-4 software and entered in an excel sheet for
further analysis. Data was also screened for outliers and tested for
normality and then analyzed using SPSS version 24. Chi-square test was
applied for categorical variables and t-test/RM ANOVA was/were
applied for numerical variables.
3. Results
The trial profile is depicted in the CONSORT flowchart in Fig. 1.
Out of 581 subjects screened, 402 were eligible and 51 subjects
agreed to participate in the study with randomization to Yoga therapy or
a waitlist group. At the end of the trial, 24 subjects were available in the
yoga group & 22 subjects in the waitlist group for analysis.
3.1. Baseline & Sociodemographic data
Subjects were compared for age, sex, marital status, years of
5
Asian Journal of Psychiatry 62 (2021) 102731
education, duration of illness, illness severity, medication dosage (CPZ
equivalents), clinical symptoms, and social and functioning level at
baseline. All the variables were comparable at baseline for the yoga and
waitlist group (Table 1).
3.2. Social cognition & clinical symptoms
Data was normally distributed and Repeated Measures Analysis of
Variance (RM ANOVA) was applied with time and group as within and
between factors respectively allowing 5% type one error. There was
significant main effect of time for social cognition composite score
(SCCS) (F = 44.69 [1,44], P < 0.001), negative symptoms (SANS) (F =
100.69 [1,45], P < 0.001), positive symptoms (SAPS) (F = 58.66 [1,45],
P < 0.001) and social disability score (GSDS) (F = 69.85 [1,46], P <
0.001). The interaction effect between time and group was also signif­
icant for SCCS (F = 42.09 [1,44], P < 0.001); SANS (F = 74.91 [1,45], P
< 0.001); SAPS (F = 16.05 [1,45], P < 0.001) and GSDS (F = 29.91
[1,46], P < 0.001) (Refer Table 2 and Fig. 2).
3.3. MNS-activity
Data were analyzed with Repeated Measures ANOVA with time and
group as within & between factors for all the MNS-activity calculated for
the two groups. MNS-activity calculated with SI1 mV in neutral action-
observation (NA) paradigm shown increment in both YTG and WL
groups but of no statistically significant difference from their baseline.
R. Govindaraj et al.
Fig. 2. Boxplot pre-post intervention data.
MNS-activity calculated with SI1 mV in Context-based action-observa­
tion paradigm (CA) paradigms had increased in the WL group and
decreased in YT but of no statistically significant difference from their
baseline. There was no significant interaction effect between time and
group for MNS-activity measured by NA & CA paradigm (Refer Table 2).
3.4. Adverse effect due to yoga
None of the subjects reported any adverse effect following yoga
intervention.
4. Discussion
This is one of the first studies exploring the role of yoga in social
cognition mediated by MNS activity. Previous studies (Jayaram et al.,
2013; Behere et al., 2011) have shown that yoga improves Facial
Emotion Recognition Deficit (FERD) in PWS. In the current study, social
cognition was measured as a composite score which included compre­
hensive coverage of ToM (1st order and 2nd order), FERD, Social
Perception, and Attribution Style (AS) besides facial emotion recogni­
tion deficit (FERD). Though we assessed AS, it was not included in the
composite score calculation, as it gives information about the style of
attribution but not a quantitative metric of good or poor cognition that
could be clubbed with other indices like ToM or social perception to
arrive at a composite score for social cognition (Mehta et al., 2011).
Our results indicate that PWS who received the yoga intervention
over 6-weeks showed significant improvement in social cognition per­
formance as compared to those in the waitlist group. From patients’
perspective, our results suggest that they could engage better in their
day to day social interactions, which forms one of the vital aspect of an
6
Asian Journal of Psychiatry 62 (2021) 102731
individual’s role functioning in the society. All cognitive assessments
were performed using objective rating instruments, which were stan­
dardized for use in the Indian socio-cultural setting. Hence, the results
may not be influenced by rater bias. It is however possible that the
improvement in social cognition could be driven by frequent social in­
teractions (Gallese, 2009) while the subjects attended their yoga ther­
apies – this frequent socialization was unlikely to be present in the
waitlist group, although we did not measure how frequently PWS in the
waitlist group interacted socially. Nevertheless, yoga is a culturally
accepted practice, and improving cognition and real-world functioning
by means of enhanced socialization, in the context of ongoing yoga
therapies is also likely to be of value to the patients and clinicians alike.
Similarly, the physical exercise component of yogasana could also have
contributed to the enhancement in social cognition in the intervention
group, which was not studied in this research, as we had only a waitlist
control group.
Beyond the non-specific effects of meeting a therapist and other
participants during yoga therapy, there could be possible yoga-specific
effects that could drive social cognitive gains in our participants. The
yoga module for schizophrenia used in this study primarily focuses on
coordinating body postures with breathing while encouraging an in­
ternal monitoring process as individuals perform these asanas. The latter
process is likely to modulate brain regions that are associated with self-
processing, self-reflection, and mentalization such as medial prefrontal
and posterior cingulate cortices. The process of performing coordinated
body postures includes imitating the trainer and experiencing one’s own
movements and postures being imitated by others in the training group.
This iterative process of imitating and being imitated is likely to facili­
tate the release of oxytocin (Delaveau et al., 2015). Our prior experi­
ments on yoga reveal that serum oxytocin levels do increase after yoga
R. Govindaraj et al.
therapy as compared to exercise (Jayaram et al., 2013). In addition, the
administration of intranasal oxytocin in healthy subjects enhances pu­
tative mirror neuron system activity in the sensorimotor cortices (Perry
et al., 2010). Yoga therapy could hence activate the mirror neuron
system – a key hub within the social brain system that drives social in­
ferences in goal-directed actions through a process of embodied simu­
lation (Gallese, 2009). Our study results not showing improvement in
MNS activity following yoga intervention could be due to a) only a
subset of participants (n = 30) consented for the measurement of MNS,
perhaps the sample size was not large enough to demonstrate statisti­
cally significant changes b) duration and intensity of yoga practice
might not be adequate enough to bring the change in MNS activity c) the
TMS paradigms used to measure MNS activity may not be sensitive
enough to capture the changes following yoga intervention, though the
same MNS activity paradigm could elicit MNS activity in healthy vol­
unteers & PWS in a previous study (Bagewadi et al., 2018)
Though our study results had not shown significant improvement in
MNS-activity following add-on yoga therapy, it is worth further explo­
ration with a larger sample in future studies, as MNS activity is proposed
as an underlying mechanism for action understanding and social
cognition (Gallese et al., 2004; Iacoboni et al., 2005). Perhaps along
with MNS activity, other cortical reactivity measures like cortical silent
period (CSP) could be assessed in the patient population in future
studies, as previous studies in healthy volunteers and depression (Jakhar
et al., 2019) had shown improvement in CSP following yoga or medi­
tation(Govindaraj et al., 2018). Given that, there is a fairly consistent
report of improved social cognition with yoga therapy, this combined
effect of yoga on core social physiological processes relevant to social
cognition and schizophrenia (Mehta et al., 2016) may be examined in
future studies.
In addition to showing social cognitive gains, the results of this study
are consistent with previous studies (Duraiswamy et al., 2007; Var­
ambally et al., 2012; Jayaram et al., 2013; Behere et al., 2011) which
show that yoga is useful in improving negative symptoms (measured by
SANS) more than the positive symptoms (measured by SAPS).
Improvement in the social functioning along with the negative symp­
toms following yoga suggests that these may be related to each other as
evidenced by a prior study (Behere et al., 2011), nonetheless we did not
find them correlated with each other and also with social cognitive gain
(improvement in routine social interactions) in our study. Although
some of the previous studies have shown improvement in positive
symptoms (Duraiswamy et al., 2007), our study results did not show
statistically significant improvement.
The results of this study are very relevant from a clinical perspective
as there are no effective pharmacological or biological treatments to
manage the cognitive dysfunction, especially social cognitive deficit in
PWS. Future studies also could explore how long the effects of add-on
yoga therapy on social cognition persist, as our current study was
designed with only one month follow up. Additionally increased dose of
yoga intervention (>20 sessions) may also be explored in subsequent
trials to identify the dose-response relationship. We examined short-
term social cognitive benefits with 20 sessions of add-on yoga therapy,
replication of these results in future trials with a larger sample size, and
long-term follow-up design would facilitate clinicians to use add-on
yoga therapy in routine clinical practice.
Funding
This research received no specific grant from any funding agency,
commercial or not-for-profit sectors.
Transparency document
The Transparency document associated with this article can be found
in the online version.
7
Asian Journal of Psychiatry 62 (2021) 102731
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgement
The authors would like to acknowledge the participants and the
wider study team. Dr Mehta is supported by the Wellcome Trust/DBT
India Alliance Early Career Fellowship, Grant/Award Number: IA/E/
12/1/500755. Dr Varambally is supported by the Wellcome Trust/DBT
India Alliance Intermediate Fellowship, Grant/Award Number: IA/
CPHI/15/1/502026.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.ajp.2021.102731.
References
Abbott, A., 2010. The drug deadlock. Nature 468, 158.
American Psychiatric Association, 2013. Diagnostic and Statistical Manual of Mental
Disorders, DSM-5. Ed. Arlington. American Psychiatric Publishing.
Andreasen, N., 1984a. Scale for the Assessment of Negative Symptoms (SANS).
University of Iowa, Iowa City.
Andreasen, N., 1984b. Scale for the Assessment of Positive Symptoms (SAPS). University
of Iowa, Iowa City.
Bagewadi, V.I., Mehta, U.M., Naik, S.S., Govindaraj, R., Varambally, S., Arumugham, S.
S., Naveen Kumar, C., Thirthalli, J., 2018. Diminished modulation of motor cortical
reactivity during context-based action observation in schizophrenia. Schizophr. Res.
https://doi.org/10.1016/J.SCHRES.2018.07.043.
Behere, R.V., Raghunandan, V., Venkatasubramanian, G., Subbakrishna, D.K.,
Jayakumar, P.N., Gangadhar, B.N., 2008. Trends-A tool for recognition of emotions
in neuropsychiatric disorders. Indian J. Psychol. Med. 30, 32.
Behere, R.V., Arasappa, R., Jagannathan, A., Varambally, S., Venkatasubramanian, G.,
Thirthalli, J., Subbakrishna, D.K., Nagendra, H.R., Gangadhar, B.N., 2011. Effect of
yoga therapy on facial emotion recognition deficits, symptoms and functioning in
patients with schizophrenia. Acta Psychiatr. Scand. 123, 147–153.
Bhatia, T., Mazumdar, S., Wood, J., He, F., Gur, R.E., Gur, R.C., Nimgaonkar, V.L.,
Deshpande, S.N., 2017. A randomised controlled trial of adjunctive yoga and
adjunctive physical exercise training for cognitive dysfunction in schizophrenia. Acta
Neuropsychiatr. 29, 102–114. https://doi.org/10.1017/neu.2016.42.
Brothers, L., 1990. The neural basis of primate social communication. Motiv. Emot. 14,
81–91.
Buckley, P.F., Stahl, S.M., 2007. Pharmacological treatment of negative symptoms of
schizophrenia: therapeutic opportunity or Cul-de-sac? Acta Psychiatr. Scand. 115,
93–100.
Corrigan, P.W., Green, M.F., 1993. Schizophrenic patients’ sensitivity to social cues: the
role of abstraction. Am. J. Psychiatry.
Couture, S.M., Penn, D.L., Roberts, D.L., 2006. The functional significance of social
cognition in schizophrenia: a review. Schizophr. Bull. 32, S44–S63.
Cramer, H., Lauche, R., Klose, P., Langhorst, J., Dobos, G., 2013. Yoga for schizophrenia:
a systematic review and meta-analysis. BMC Psychiatry 13, 32.
Delaveau, P., Arzounian, D., Rotgé, J.-Y., Nadel, J., Fossati, P., 2015. Does imitation act
as an oxytocin nebulizer in autism spectrum disorder? Brain 138 e360–e360.
Drury, V.M., Robinson, E.J., Birchwood, M., 1998. ‘Theory of mind’skills during an acute
episode of psychosis and following recovery. Psychol. Med. 28, 1101–1112.
Duraiswamy, G., Thirthalli, J., Nagendra, H.R., Gangadhar, B.N., 2007. Yoga therapy as
an add-on treatment in the management of patients with schizophrenia–a
randomized controlled trial. Acta Psychiatr. Scand. 116, 226–232.
Festante, F., Ferrari, P.F., Thorpe, S.G., Buchanan, R.W., Fox, N.A., 2020. Intranasal
oxytocin enhances EEG mu rhythm desynchronization during execution and
observation of social action: an exploratory study. Psychoneuroendocrinology 111,
104467.
Fett, A.-K.J., Viechtbauer, W., Penn, D.L., van Os, J., Krabbendam, L., 2011. The
relationship between neurocognition and social cognition with functional outcomes
in schizophrenia: a meta-analysis. Neurosci. Biobehav. Rev. 35, 573–588.
Gallese, V., 2009. Mirror neurons, embodied simulation, and the neural basis of social
identification. Psychoanal. Dialogues 19, 519–536.
Gallese, V., Keysers, C., Rizzolatti, G., 2004. A unifying view of the basis of social
cognition. Trends Cogn. Sci. (Regul. Ed.) 8, 396–403.
Gothe, N.P., McAuley, E., 2015. Yoga and cognition: a meta-analysis of chronic and acute
effects. Psychosom. Med. 77, 784–797. https://doi.org/10.1097/
PSY.0000000000000218.
Govindaraj, R., Varambally, S., Sharma, M., Gangadhar, B.N., 2016. Designing and
validation of a yoga-based intervention for schizophrenia. Int. Rev. Psychiatry 1–4.
https://doi.org/10.3109/09540261.2016.1151404.
Govindaraj, R., Mehta, U.M., Kumar, V., Varambally, S., Thirthalli, J., Gangadhar, B.N.,
2018. Effect of yoga on cortical inhibition in healthy individuals: a pilot study using
R. Govindaraj et al.
transcranial magnetic stimulation. Brain Stimulation: Basic, Translational, and
Clinical Research in Neuromodulation. https://doi.org/10.1016/j.brs.2018.08.017.
Green, M.F., Penn, D.L., Bentall, R., Carpenter, W.T., Gaebel, W., Gur, R.C., Kring, A.M.,
Park, S., Silverstein, S.M., Heinssen, R., 2008. Social cognition in schizophrenia: an
NIMH workshop on definitions, assessment, and research opportunities. Schizophr.
Bull. 34, 1211–1220.
Guy, W., 2000. Clinical Global Impressions (CGI) Scale. Modified From: Rush J, et al.:
Psychiatric Measures. APA, Washington DC.
Iacoboni, M., Molnar-Szakacs, I., Gallese, V., Buccino, G., Mazziotta, J.C., Rizzolatti, G.,
2005. Grasping the intentions of others with one’s own mirror neuron system. PLoS
Biol. 3, e79.
Insel, T.R., 2015. The NIMH experimental medicine initiative. World Psych. 14, 151.
Jakhar, J., Mehta, U.M., Ektare, A., Vidyasagar, P.D., Varambally, S., Thirthalli, J.,
Gangadhar, B.N., 2019. Cortical inhibition in major depression: investigating the
acute effect of single-session yoga versus walking. Brain Stimul. 12, 1597–1599.
Jayaram, N., Varambally, S., Behere, R., Venkatasubramanian, G., Arasappa, R.,
Christopher, R., Gangadhar, B., 2013. Effect of yoga therapy on plasma oxytocin and
facial emotion recognition deficits in patients of schizophrenia. Indian J. Psychiatry
55, 409–413. https://doi.org/10.4103/0019-5545.116318.
Kinderman, P., Bentall, R.P., 1996. A new measure of causal locus: the internal, personal
and situational attributions questionnaire. Pers. Individ. Dif. 20, 261–264.
Kurtz, M.M., Gagen, E., Rocha, N.B.F., Machado, S., Penn, D.L., 2016. Comprehensive
treatments for social cognitive deficits in schizophrenia: a critical review and effect-
size analysis of controlled studies. Clin. Psychol. Rev. 43, 80–89.
McClintock, S.M., Freitas, C., Oberman, L., Lisanby, S.H., Pascual-Leone, A., 2011.
Transcranial magnetic stimulation: a neuroscientific probe of cortical function in
schizophrenia. Biol. Psychiatry 70, 19–27.
Mehta, U.M., Thirthalli, J., Kumar, C.N., Mahadevaiah, M., Rao, K., Subbakrishna, D.K.,
Gangadhar, B.N., Keshavan, M.S., 2011. Validation of Social Cognition Rating Tools
in Indian Setting (SOCRATIS): a new test-battery to assess social cognition. Asian J.
Psychiatr. 4, 203–209.
Mehta, U.M., Thirthalli, J., Subbakrishna, D.K., Gangadhar, B.N., Eack, S.M.,
Keshavan, M.S., 2013. Social and neuro-cognition as distinct cognitive factors in
schizophrenia: a systematic review. Schizophr. Res. 148, 3–11.
Asian Journal of Psychiatry 62 (2021) 102731
Mehta, U.M., Thirthalli, J., Basavaraju, R., Gangadhar, B.N., Pascual-Leone, A., 2014.
Reduced mirror neuron activity in schizophrenia and its association with theory of
mind deficits: evidence from a transcranial magnetic stimulation study. Schizophr.
Bull. 40, 1083–1094.
Mehta, U.M., Keshavan, M.S., Gangadhar, B.N., 2016. Bridging the schism of
schizophrenia through yoga—review of putative mechanisms. Int. Rev. Psychiatry
28, 254–264.
NICE, 2014. Psychosis and Schizophrenia in Adults: Prevention and Management. NICE.
Penn, D.L., Sanna, L.J., Roberts, D.L., 2008. Social cognition in schizophrenia: an
overview. Schizophr. Bull. 34, 408–411.
Perner, J., Wimmer, H., 1985. John thinks that Mary thinks that…” attribution of second-
order beliefs by 5-to 10-year-old children. J. Exp. Child Psychol. 39, 437–471.
Perry, A., Bentin, S., Shalev, I., Israel, S., Uzefovsky, F., Bar-On, D., Ebstein, R.P., 2010.
Intranasal oxytocin modulates EEG mu/alpha and beta rhythms during perception of
biological motion. Psychoneuroendocrinology 35, 1446–1453.
Sheehan, D., Lecrubier, Y., Sheehan, K.H., Sheehan, K., Amorim, P., Janavs, J.,
Weiller, E., Hergueta, T., Baker, R., Dunbar, G., 1998. Diagnostic psychiatric
interview for DSM-IV and ICD-10. J. Clin. Psychiatr. 59, 22–33.
Stone, V.E., Baron-Cohen, S., Knight, R.T., 1998. Frontal lobe contributions to theory of
mind. J. Cogn. Neurosci. 10, 640–656.
Varambally, S., Gangadhar, B., Thirthalli, J., Jagannathan, A., Kumar, S.,
Venkatasubramanian, G., Muralidhar, D., Subbakrishna, D., Nagendra, H., 2012.
Therapeutic efficacy of add-on yogasana intervention in stabilized outpatient
schizophrenia: randomized controlled comparison with exercise and waitlist. Indian
J. Psychiatry 54, 227–232. https://doi.org/10.4103/0019-5545.102414.
Wassermann, E., Epstein, C., Ziemann, U., Walsh, V., Paus, T., Lisanby, S., 2008. Oxford
Handbook of Transcranial Stimulation. Oxford Library of Psychology, OUP Oxford.
Wiersma, D., DeJong, A., Ormel, J., 1988. The groningen social disabilities schedule:
development, relationship with ICIDH, and psychometric properties. Int. J. Rehabil.
Res. 11, 213–224.
Wimmer, H., Perner, J., 1983. Beliefs about beliefs: representation and constraining
function of wrong beliefs in young children’s understanding of deception. Cognition
13, 103–128.