RNN 170810

Restorative Neurology and Neuroscience xx (20xx) x–xx 1
DOI 10.3233/RNN-170810
IOS Press
Original Research Article
Yoga- and meditation-based lifestyle

intervention increases neuroplasticity
and reduces severity of major depressive
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disorder: A randomized controlled trial
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Madhuri R. Tolahunasea , Rajesh Sagarb , Muneeb Faiqa and Rima Dadaa,∗
a Department of Anatomy, Lab for Molecular Reproduction and Genetics, All India Institute
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of Medical Sciences (AIIMS), New Delhi, India
b Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), New Delhi, India
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Abstract.
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Background: Current interventions for major depressive disorder (MDD) are suboptimal, and only one third respond to them
on initial treatment. Neuroplasticity theories are the basis for several emerging treatments. Evidence on the impact of yoga,
a well-known mind-body intervention, on neuroplasticity in MDD is limited.
Objectives: To determine the effects of 12-week yoga- and meditation- based lifestyle intervention (YMLI) on depression
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severity and systemic biomarkers of neuroplasticity in adult MDD patients on routine drug treatment.
Methods: A total of 58 MDD patients were randomized into yoga or control group. The severity of depression was assessed
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with Beck Depression Inventory II scale (BDI-II). Blood samples were collected before and after intervention for the
measurement of the biomarkers that characterize neuroplasticity, including mind-body communicative and cellular health
biomarkers.
Results: There was a significant decrease [difference between means, (95% CI)] in BDI-II score [–5.83 (–7.27, –4.39),
or
p < 0.001] and significant increase in BDNF (ng/ml) [5.48 (3.50, 7.46), p < 0.001] after YMLI compared to control group.
YMLI significantly increased DHEAS, sirtuin 1, and telomerase activity levels, and decreased cortisol, and IL-6 levels, in
addition to decreasing DNA damage and balancing oxidative stress. Multiple regression analyses were used to associate
neuroplasticity biomarkers with depression severity. A ‘post-intervention change in BDNF’ x ‘group’ interaction indicated
that yoga group had more BDNF in association with less BDI-II scores relative to controls. Increased sirtuin 1 and telomerase
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activity and decreased cortisol significantly predicted this association (all p < 0.05).
Conclusion: These results suggest that decrease in depression severity after YMLI in MDD is associated with improved
systemic biomarkers of neuroplasticity. Thus YMLI can be considered as a therapeutic intervention in MDD management.
Keywords: Depression, Major depressive disorder, Yoga, Oxidative stress, BDNF, Sirtuin 1, Telomere
1. Introduction
∗ Corresponding author: Dr Rima DADA, M.D., Ph.D. (Genet-

Major depressive disorder (MDD) is a modern
ics), MAMS Professor, Lab for Molecular Reproduction and world pandemic, affecting both mind and body
Genetics, Department of Anatomy, All India Institute of Med-
ical Sciences (AIIMS), New Delhi -110029, India. E-mails:
(Penninx et al., 2013). It has become the largest con-
rima dada@yahoo.co.in and rima dada@rediffmail.com tributor to the global burden of disease (Ferrari et al.,
0922-6028/18/$35.00 © 2018 – IOS Press and the authors. All rights reserved
2 M.R. Tolahunase et al. / Yoga increases neuroplasticity in depression
2013; Korsager Larsen & Matchkov, 2016; World recent studies have shown clinical benefits of yoga in
Health Organization, 2016) with a worldwide preva- MDD (Cramer et al., 2017; Prathikanti et al., 2017),
lence of 9–36% and is associated with an increase surprisingly, there are few studies examining how
in mortality risk by 60–80% (Cuijpers et al., 2014; yoga- and meditation-based interventions affect sys-
Penninx et al., 2013; Walker et al., 2015). Accel- temic biomarkers of neuroplasticity in MDD. In this
erated cellular aging associated with this disorder regard, Naveen et al. (2016) showed a significant pos-
(Sibille, 2013; Verhoeven et al., 2014) contributes itive correlation between the decrease in depression
to decreased neuroplasticity (Player et al., 2013) severity and rise in serum BDNF and reduced cor-
and impaired mood, cognition, and somatic health tisol levels in MDD patients after yoga practice for
(Verhoeven et al., 2014). Current first-line treatment 12 weeks. Recently, studies have also reported the
based on monoamine hypothesis has failed to explain benefits of yoga in improving multiple biomarkers
the pathobiology of MDD thoroughly and provides that have an impact on neuroplasticity, in apparently
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remission only in approximately one-third of the healthy (Qu et al., 2013; Tolahunase et al., 2017) and
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patients (Kuhn et al., 2014) on treatment initiation. stressed individuals (Harkess et al., 2016).
Considering the limited and suboptimal remission, Neuroplasticity is the ability of the central nervous
frequent relapses, and complications associated with system (CNS) to adapt and reorganize its structure
it, new theories of depression are emerging, and and function in response to internal or external stim-
improving neuroplasticity has become the basis for uli and manifests at both biological and clinical
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many new treatments (Cramer et al., 2011; Gerhard et levels. The high-level of plasticity, which makes hip-
al., 2016). These emerging treatments include passive pocampus and other regions of the CNS affected by
interventions like ketamine and repetitive transcra- MDD vulnerable to neurodegeneration (Bartsch &
nial magnetic stimulation (rTMS) (Gerhard et al., Wulff, 2015), suggests that it is equally modifiable
2016). The long-term biological and clinical effects by interventions. Systemic biomarkers dynamically
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of these interventions are unknown, and the patients reflect biology in the brain, including neuroplastic-
may suffer from severe irreversible complications ity (Liew, Ma et al., 2006), and the relationship
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(Corlett et al., 2006; Morgan et al., 2004; Wassermann between peripheral blood and brain across various
& Zimmermann, 2012). Interventions that provide domains of analysis provide a context for evaluat-
a long-lasting improvement in neuroplasticity and ing systemic biomarkers in MDD. The pathobiology
characterize the mechanisms which determine opti- which can influence neuroplasticity is associated
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mum neuroplasticity in regions of the brain affected with modifications in several mechanisms, including
by MDD warrant further research. - neurotransmission; neuroendocrine, immune, and
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Yoga is a mind-body intervention (MBI) that has metabolic regulations; the microbiota and the gut-
become increasingly popular worldwide. Yoga is a brain axis; and the gene-environment interactions.
profound science for wellbeing and disease man- Novel systemic biomarkers of neuroplasticity that
agement. Biopsychosocial principles underlie the are associated with these processes include: BDNF
or
practice of yoga, and the accumulating evidence (brain derived neurotrophic factor) (Autry & Mon-
suggests that it has a positive impact on both men- teggia, 2012; Bocchio-Chiavetto et al., 2010), sirtuin1
tal and physical health (Büssing et al., 2012). A (Abe et al., 2011; Jesko et al., 2017), cortisol (Vree-
recent meta-analysis (Goldberg et al., 2018) sup- burg et al., 2009), IL-6 (Zhang et al., 2016), DHEAS
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port the notion that mindfulness-based interventions (dehydroepiandrosterone sulfate) (Uh et al., 2017),
hold promise as evidence-based treatments for psy- and also the markers of oxidative stress (Liu et
chiatric disorders and showed the most consistent al., 2015), DNA damage (Czarny et al., 2015), and
evidence in support of mindfulness for depres- telomere metabolism (Henje Blom et al., 2015). As
sion. Regular practitioners of yoga and meditation several imaging studies suggest that the practice of
showed a reduced age-associated decline in gray mat- yoga and meditation altered the regional brain vol-
ter, which is an index of optimum neuroplasticity umes and functional brain circuits (Froeliger et al.,
(Froeliger et al., 2012; Villemure et al., 2015). Recent 2012; Hölzel et al., 2011), they presumably could
studies have shown that practice of yoga and affect neuroplasticity. However, current evidence is
meditation, even for short duration, can increase neu- limited regarding how yoga practice affects the sys-
roplasticity in the brain of both healthy individuals temic biomarkers of neuroplasticity, especially in
(Hölzel et al., 2011) and patients with neuropsychi- MDD. Evidence suggests that these novel biomark-
atric conditions (Eyre et al., 2016). Although several ers improve with MBIs, comprising either or both
M.R. Tolahunase et al. / Yoga increases neuroplasticity in depression 3
physical and mental components, in a spectrum subjects having other co-morbid neuropsychiatric
of clinical and experimental conditions, and have and chronic medical conditions, including bipolar
resulted in increased neuroplasticity (Bayod et al., disorder, hypertension, diabetes mellitus that secon-
2012; Boccatonda et al., 2016; Campbell et al., 2010; darily have co-morbid depression.
Duraimani et al., 2015; Hofer et al., 2008; Ornish et
al.; Szuhany et al., 2015; Villanova et al., 2013). 2.3. Interventions
With this context in mind, the primary aim of
the present study was to determine the effects of a A total of 58 participants were randomized
12-week Yoga- and meditation-based lifestyle inter- into yoga or control group, after recruiting and
vention (YMLI) on depression severity and systemic screening eligible subjects. Baseline characteristics
biomarkers of neuroplasticity. Our study included a were recorded before the intervention. Participants
combination of biomarkers that characterize neuro- underwent a 12-week pre-tested YMLI program com-
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plasticity in MDD patients that include: the cardinal prising theory and practice sessions (Tolahunase et
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biomarker of neuroplasticity – BDNF; mind-body al., 2017). YMLI program included sessions five days
communication biomarkers – cortisol, IL-6, DHEAS, per week and was suitably modified for MDD patients
and sirtuin 1; and biomarkers of cellular health in the current study. The sessions were taught by
– oxidative stress (reactive oxygen species, ROS registered, specialized yoga instructors at the inte-
and total antioxidant capacity, TAC), DNA damage grated health clinic (IHC), AIIMS, New Delhi. The
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(8OH2dG), and telomere metabolism (telomerase details of the activities during YMLI program are
activity and telomere length). given in Table 1. Each session in YMLI included a set
of asanas (physical postures), pranayama (breathing
exercises), and dhyana (meditation) for approxi-
2. Materials and methods mately 120 minutes. YMLI included interactive
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lectures on lifestyle, lifestyle diseases, MDD, and
2.1. Trial Design the importance of their prevention. The Hawthorne
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effect was insignificant because of YMLI’s emphasis
The study was a single-arm parallel-randomized on environmental enrichment and self-awareness.
controlled trial analyzing the effects of a 12-week
YMLI on depression severity and systemic biomark- 2.4. Outcomes
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ers of neuroplasticity in MDD patients on routine

drug therapy. The intervention period was from April The primary outcome was to assess the change
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2015 to September 2016. The study was initiated in severity of MDD [Beck Depression Inventory –II
after ethical clearance (ESC/T-370/22-07-2015) from scale (BDI-II) scores)] from baseline to week 12. The
the institutional ethics committee and the registra- composite primary outcome was to assess the change
tion of the trial (Clinical Trial Registry of India in the levels of blood biomarkers related to neuro-
or
(CTRI) REF/2014/09/007532). CTRI is one among plasticity that included: the cardinal biomarker of
the primary registries of the International Clinical Tri- neuroplasticity – BDNF; mind-body communicative
als Registry Platform (ICTRP) of the World Health biomarkers – sirtuin 1, cortisol, IL-6, and DHEAS;
Organization (World Health Organization, 2018). All and biomarkers of cellular health – oxidative stress
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participants provided signed informed consent. The markers (reactive oxygen species, ROS and total
data were reported according to CONSORT state- antioxidant capacity, TAC), DNA damage marker
ment (Moher et al., 2010). (8OH2dG), and telomere metabolism (telomerase
activity and telomere length).
2.2. Participants, eligibility criteria, and settings
2.5. Sample size calculation
Participants were recruited from the outpatient unit
of Psychiatry department of AIIMS, New Delhi. The The sample size calculation was based on the find-
study inclusion criteria included age 19–50 years old ings from previous publications of other research
MDD patients diagnosed with DSM-5 criteria and groups who have shown beneficial effects of yoga
on routine drug treatment for at least six months. with similar sample size (Sarubin et al., 2014). Cal-
The exclusion criteria included subjects having very culations assumed two-tailed ␣ = 0.05 and 1-␤ = 80%
severe depression (BDI-II scale score ≥45), and to detect a 20% difference.
Table 1
Details of activities of the Yoga and Meditation based Lifestyle Intervention (YMLI) program
S. No. Practice to be done Duration
(1) Session preparation instructions 2 min
(2) Prayer 2 min
Loosening practices (warm-up) 5 min
(3) Sūrya Namaskāra (Sun Salutation) 5 min
Shavasana 2 min
Supine Uttanpadasana 2 min
Pawanmuktasana 2 min
Makarāsana 2 min
Prone Bhujangasana 2 min
(4) Asanas (Postures) Salabhasana 2 min
Vakrasana 2 min
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Sitting U rāsana 2 min
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paścimottānāsana 2 min
Parivrtta Trikonasana 2 min
Standing Vrikshasana 2 min
Ardhachakrasana 2 min
(5) Relaxation Shavasana 2 min
Nadishodhana
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Ujjayi
(6) Pranayama (Breathing Exercises) Shitkari 20 min
Shitali
Brahmamudra
(7) Aumkar recitation 3 min
(8) Dhyana (Meditation) 20 min
(9) Shanti Mantra 5 min
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(10) Interactive session / Self-directed learning 30 min
Total 120 min
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2.6. Randomization and blinding allowed to clot, and the serum was separated within
30 min, and the other part was transferred to hep-
Computer-generated random numbers were used arinized and EDTA vials and was centrifuged at
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for randomization with unrestricted equal partici- 2000 g for 15 minutes at 4◦ C. Both serum and plasma
pant allocation, with the assistance of the web tool were stored at –80◦ C until analyzed.
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research randomizer (https://www.randomizer.org/), ROS detection was done by chemiluminescence

and with the participants not blinded to the study. A assay (Berthold detection luminometer, USA). TAC
research assistant not otherwise involved in the study was estimated by a colorimetric assay (Cayman
or
created the randomization allocation schedule. Chemical, Ann Arbor, USA). Telomerase activity
was determined by using a telomerase assay kit
2.7. Measurement of clinical parameters (Roche, Switzerland) as per the manufacturer’s pro-
tocol. Peripheral blood leucocyte telomere length
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The severity of depression was assessed with BDI- was measured by the qPCR method. 8-OH2dG was
II scale, which is considered a clinically useful estimated in white blood cell DNA (Cayman’s EIA
criterion and is widely accepted in MDD trials as kit). ELISA kits were used for the levels of BDNF
the primary outcome (Frank et al., 1991; Freedland (Raybiotech, Inc), sirtuin 1 (Qayee Bio-Technology),
et al., 2015; Reeves et al., 2012). DHEAS (Qayee Bio-Technology), cortisol (DRG
Diagnostic, Germany), and IL-6 (Gen-Probe, Dia-
clone Diagnostic, France). Quality-control assays for
2.8. Measurement of blood biomarkers related biomarkers and validation were performed.
to neuroplasticity
During this 12-week study, the participants were 2.9. Statistical analysis
evaluated for various biomarkers at baseline and
week 12. Fasting venous blood samples (5 mL) were Tests were conducted using SPSS 23.0 (SPSS
collected and divided into two parts. One part was Inc., Chicago, IL) at an ␣ of 0.05 using primary
Table 2 BDI-II score [–5.83 (–7.27, –4.39), p < 0. 001] and

Baseline characteristics significant increase in BDNF (ng/ml) [5.48 (3.50,
Variable Group p-Value 7.46), p < 0. 001] after YMLI compared to con-
Yoga (n = 29) Control (n = 29) trol group. Among the mind-body communicative
Age (years) 36.94 (8.94) 39.10 (9.26) 0.370 biomarkers, there was a significant increase in circu-
Sex lating DHEAS and sirtuin 1 and a significant decrease
Female 16 (55.2) 15 (51.7) 0.792
Male 13 (44.8) 14 (48.3) 0.814
in circulating cortisol and IL-6 after YMLI com-
Kuppuswamy 16.98 (6.94) 17.26 (8.56) 0.861 pared to yoga group at baseline level and control
SES scale group. A total of 12 weeks YMLI showed improve-
BMI 26.18 (5.94) 27.10 (6.26) 0.568 ment in cellular health biomarkers that included -
Depression severity
BDI-II score 26.96 (6.92) 28.10 (7.56) 0.550 significant decrease in 8OH2dG (marker of DNA
damage); significant increase in TAC and decrease
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Data were described as frequency (%) for sex and mean (SD) for
others. SES, socioeconomic status. in ROS (markers of oxidative stress); and significant
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increase in telomerase activity (marker of telomere
attrition) compared to control group (all p < 0. 05)
intent-to-treat analysis (ITT) approach, with the base- (Table 3). However, change in telomere length was
line observation carried forward (BOCF). We used not significant in both groups. Also, the control group
chi-square test and Fisher’s exact test to compare cat- showed significantly increased ROS and IL-6 levels
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egorical characteristics at baseline; we used student’s compared to baseline (P < 0.001).
t-test to compare normally distributed continuous
variables and the Wilcoxon rank-sum test to compare 3.3. Group × gender interactions
nonparametric continuous data (Table 2). Within-
group changes over time (pre- to post-intervention) Men were significantly more depressed at base-
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were evaluated using paired t-tests for continu- line than women (BDI-II scores 30.4 ± 7.82 and
ous variables, or Wilcoxon signed rank test for 26.10 ± 8.26 mean ± SD respectively). Three-way
continuous variables without normal distribution.
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interactions including group and gender indicated
Between-group differences over time were assessed favorable responses to YMLI for men for DHEAS
using independent samples t-test. Mixed factorial (F(1,54) = 5.02; p < 0.03). Separate analyses for
design ANOVA was used to assess gender differ- males and females were, therefore, performed to
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ences. Multiple regression was used to determine overcome baseline violations in depression severity
the change in which variables significantly explained and to explore further specific gender effects. Clini-
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the association and interaction of neuroplasticity and cal improvement was more significant for the women
change in depression severity. in yoga group (mean between-group difference of
change: Female = –6.12, F(1,29) = 10.81, p = 0.003;
Male –3.86, F(1,25) = 5.14, p = 0.032 (Fig. 3).
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3. Results
3.4. Association of depression severity, BDNF,
3.1. Participants’ flow and baseline and biomarkers of mind-body
characteristics communication and cellular health
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Participants (n = 58) were randomly assigned to Since neuroplasticity influences depression sever-
yoga or control groups. Figure 1 shows the CON- ity, we planned to analyze the relationship between
SORT flowchart of intervention. No harmful effects BDNF, the cardinal marker of neuroplasticity, and
were observed by YMLI. There were no significant depression severity. Figure 3A depicts the correla-
differences in baseline characteristics between the tion between BDNF and the BDI-II scores across
two groups (Table 2). groups (R2 = 0.286; P < 0.001). Follow-up multiple
linear regression was conducted to analyze the asso-
3.2. Post-intervention differences in depression ciation of the mind-body communicative and cellular
severity and markers of neuroplasticity health biomarkers that are related to neuroplasticity.
The dependent variable was the BDNF pre-
As shown in Table 3, there was a significant dicted change in BDI-II scores. Different regression
decrease [difference between means, (95% CI)] in models using stepwise, forward, or enter methods
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Fig. 1. CONSORT flow chart of the study.

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produced similar results. The regression model pre-

dicted 18.7% of the variance across both groups
[F(9,48) = 3.960; P < 0.01]. Higher levels of cor-
tisol (R2 = 0.194; P < 0.05) and ROS (R2 = 0.178;
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P < 0.05) were associated with increased BDI-II

scores (data not shown). Since YMLI may sig-
nificantly affect neuroplasticity, we tested for the
association of change in BDI-II scores in yoga
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group in comparison to control group. Yoga group

showed greater reduction in BDI-II scores as BDNF
increased (R2 = 0.183; P < 0.05) (Fig. 3B). However,
for controls higher BDNF unexpectedly corre-
sponded to increased BDI-II scores (R2 = 0.224;
P < 0.01) (Fig. 3B). To further analyze the media-
tors that might explain the interaction of group effect,
Fig. 2. Gender interactions for change in depression severity after
the intervention. A. Mean change of BDI-II score with 95% multiple linear regression was performed in paral-
CI for men in the yoga and the control groups; p < 0.032 for lel on each intervention group. The BDNF × group
between-group difference of change in the study, adjusted for interaction predicted change in BDI-II scores was the
baseline value. B. Mean change of BDI-II score with 95% CI for
women in the yoga and the control groups; p < 0.003 for between-
dependent variable. As shown in Table 4 and Fig. 4
group difference of change on the study, adjusted for baseline A–C yoga group had strong associations between
value. cortisol, sirtuin 1, or telomerase activity and change
Table 3
Means (SE) and results of within-group and between-group analysis of systemic biomarkers of neuroplasticity (n = 58; YMLI, 29;
Control, 29)
Time 1(Baseline) Time 2 (12 week) Change Value Within Between
Time2-Time1 Group p Group p
Mean(SD) Mean(SD) Mean(CI) value1 value2
Clinical outcome for depression severity
BDI-II score
Yoga 23.17 ± 4.31 17.34 ± 6.40 –5.83 (–7.27, –4.39) <0.001 <0.001
Control 22.21 ± 4.39 23.66 ± 5.52 1.45 (0.44, 2.46) 0.007
Cardinal marker of neuroplasticity
BDNF (ng/ml)
Yoga 13.15 ± 4.27 18.63 ± 6.91 5.48 (3.50, 7.46) <0.001 <0.001
13.56 ± 4.08 13.58 ± 4.13
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Control 0.02 (–0.91, 0.95) 0.962
Mind-body communicative markers of neuroplasticity
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Cortisol (ng/ml)
Yoga 410.83 ± 24.94 245.19 ± 188.95 –165.63 (–239.01, –92.25) <0.001† <0.001
Control 417.61 ± 20.14 446.23 ± 94.81 28.62 (–6.63, 63.86) 0.412†
IL6 (pg/ml)
Yoga 3.87 ± 0.49 3.02 ± 1.29 –0.84 (–1.26, –0.42) <0.001 <0.001
Control 3.90 ± 0.47 4.48 ± 0.99 0.57 (0.25, 0.90) 0.001
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DHEAS (ng/ml)
Yoga 69.48 ± 29.67 81.18 ± 37.67 11.69 (5.35, 18.04) 0.001 0.001
Control 63.50 ± 15.01 62.35 ± 14.97 –1.15 (–2.59, 0.30) 0.115
SIRT1 (ng/ml)
Yoga 32.11 ± 2.60 38.32 ± 6.53 6.21 (3.96, 8.46) <0.001 <0.001
Control 30.31 ± 2.11 29.42 ± 2.72 –0.89 (–1.61, –0.17) 0.017
Cellular health markers of neuroplasticity
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ROS (RLU/min/104 neutrophils)
Yoga 3568.87 ± 772.81 2502.06 ± 1052.20 –1066.81 (–1406.06, –727.57) <0.001 <0.001
Control 3234.42 ± 799.17 3357.76 ± 751.26 123.34 (56.58, 190.11) <0.001†
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TAC (mmol Trolox equiv/L)
Yoga 6.19 ± 0.48 8.70 ± 2.11 2.51 (1.77, 3.25) <0.001 <0.001
Control 6.01 ± 0.34 5.80 ± 0.75 –0.21 (–0.53, 0.12) 0.203
8OH2dG (pg/ml)
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Yoga 1300.38 ± 59.31 1204.34 ± 111.33 –96.04 (–141.40, –50.68) <0.001 <0.001
Control 1305.53 ± 78.22 1340.94 ± 176.81 35.41 (–24.21, 95.03) 0.234
Telomerase activity (IU/cell)
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Yoga 22.54 ± 6.03 30.76 ± 8.16 8.22 (5.96, 10.49) <0.001 <0.001
Control 24.32 ± 4.91 23.82 ± 4.08 –0.50 (–1.32, 0.32) 0.223
Telomere length (IU/cell)
Yoga 0.60 ± 0.29 0.79 ± 0.49 0.19 (0.00, 0.38) 0.053 0.174
Control 0.51 ± 0.21 0.54 ± 0.38 0.03 (–0.10, 0.17) 0.635
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CI = Confidence interval. 1 paired samples t-test. † Wilcoxson signed rank test. 2 independent samples t-test.
in BDI-II score related to the interaction. However, severity. While yoga group showed a significant post-
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the control group showed nonsignificant relation- intervention increase of BDNF levels in comparison
ships for these variables as shown in Fig. 4 D–F and to control group, there was an unexpected trend of
Table 4. increasing BDI-II scores with increasing BDNF lev-
els in the control group. Our study also highlights
that yoga group significantly improved systemic
4. Discussion biomarkers related to neuroplasticity, including:
mind-body communicative biomarkers - sirtuin 1,
We hypothesized that YMLI reduces depression cortisol, IL-6, and DHEAS; and cellular health
severity by improving neuroplasticity, as indicated biomarkers - markers of oxidative eustress (ROS
by its systemic biomarkers. In the present study, and TAC), DNA damage (8OH2dG), and telomere
the increase in BDNF, the cardinal biomarker of metabolism (telomerase activity). Improvement in
neuroplasticity, after 12 weeks YMLI, was signif- systemic biomarkers of neuroplasticity in associa-
icantly associated with the reduction of depression tion with the positive clinical outcome of reduction
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Fig. 3. The relationship between BDNF and BDI-II (depression severity) score across participants (A) and a BDNF × group interaction
(B) testing such an association for each intervention group. indicates pre-post intervention change.
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Table 4
Significant predictors of change in BDNF x group interaction with change in BDI-II scores
Variable B SE b ␤ t
YOGA Constant –4.832 0.187
Mind-body communicative biomarkers
cortisol 0.319∗
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0.001 0.001 2.526
IL-6 0.032 0.083 0.041 0.390
DHEAS –0.003 0.005 –0.066 –0.656
Sirtuin 1 –0.393∗
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–0.058 0.022 –2.633
Cellular health biomarkers
ROS 0.000 0.000 –0.071 –0.626
TAC 0.046 0.044 0.101 1.033
8OH2dG 0.001 0.001 0.173 1.610
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Telomerase Activity –0.044 0.018 –0.296∗ –2.457

Telomere Length –0.203 0.208 –0.117 –0.976
CONTROL Constant 1.679 0.134
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Mind-body communicative biomarkers

cortisol 0.000 0.001 0.045 0.195
IL-6 –0.106 0.124 –0.217 –0.855
DHEAS 0.013 0.027 0.122 0.499
Sirtuin 1
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0.065 0.057 0.298 1.144

Cellular health biomarkers
ROS –0.001 0.001 –0.334 –1.561
TAC –0.025 0.106 –0.051 –0.233
8OH2dG 0.000 0.001 –0.089 –0.427
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Telomerase Activity 0.004 0.046 0.020 0.086

Telomere Length 0.006 0.257 0.005 0.023
Multiple regression was used to assess which mind-body communicative and cellular health variables mediated
the BDNF × group interaction effect. These variables were regressed onto the predicted BDI-II scores due to
BDNF for yoga or control groups. For the final yoga model, the adjusted R2 of the mediation model was 0.786
[F(9,19) = 12.440; P < 0.001]. For the final control mediational model, the adjusted R2 was –0.024 [F(9,19) = 0.926;
NS]. DHEAS, dehydroepiandrosterone sulfate, ROS, reactive oxygen species, TAC, total antioxidant capacity,
8OH2dG, 8-hydroxy 2’-deoxy guanosine. ∗ P ≤ 0.05. indicates a change between post-intervention and pre-
intervention values.
in clinical severity, suggests that YMLI may provide 4.1. YMLI improves neuroplasticity
long-term clinical remission in MDD, by posi-
tively modifying the pathobiology, at the level of Yoga, a premier MBI, has been increasingly
the brain, mind-body communications, and cellular accepted as a cost-effective strategy for promoting
health. physical and mental health. This is evident from the
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Fig. 4. Shown are the partial regression plots that depict error variance of the effect on change in BDI-II scores by cortisol, sirtuin 1, and
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telomerase activity in yoga and control groups. Neuroplasticity mediator variables are shown regressing on the change in BDI-II scores
predicted by change in BDNF × group interaction. Yoga and control groups are represented by circles and triangles respectively.
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reduced age-associated decline in the gray matter of systemic BDNF levels, in association with improve-
regular meditators (Froeliger et al., 2012; Hölzel et ment in biomarkers of mind-body communication
al., 2011). Recent studies and meta-analysis (Boc- and cellular health. A recent review has analyzed
c
cia et al., 2015; Fox et al., 2014) of neuroimaging how peripheral somatic stimulation by acupuncture
in meditation practitioners, found consistent alter- may increase neurotrophic factors like BDNF, and
re
ations and activations of brain areas involved in the improve neuroplasticity (Shin et al., 2017). Asanas
processing of higher mental functions. BDNF plays (postures), and pranayama (breathing exercise) in
an important role in neuroplasticity and neurogen- YMLI may provide similar peripheral stimulation
esis and is a cardinal biomarker (Thoenen, 1995), to CNS. In this regard, increased BDNF levels and
or
which positively correlate with the enhanced neuro- improved clinical outcomes by YMLI, suggest that
plasticity seen at morphometric, neural network, and it may be an intervention to improve neuroplasticity,
molecular levels. There is even a growing interest reverse pathobiology of MDD, and provide long-term
to translate BDNF biology into therapies for depres- remission.
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sion (Lu et al., 2013). Although passive interventions Evidence regarding how yoga practice affects
modify neuroplasticity (Duman & Voleti, 2012) and blood BDNF level, and increase neuroplasticity
related processes in the brain, they fail to provide remains inconsistent. On a neurobiological level,
long-term remissions and are associated with com- BDNF (Thoenen, 1995) and its signaling partners
plications (Penn & Tracy, 2012). In a recent study, (Park & Poo, 2012) have emerged as key regula-
exercise increased BDNF levels in MDD patients tors of neuroplasticity. They contribute to complex
(Kerling et al., 2017). In another study, Taekwondo, functions of the brain, like cognition and emotion, by
a form sport, and exercise, improved neuroplasticity- mediating synaptic plasticity and structural and func-
related growth factors, including BDNF, in healthy tional long-term potentiation (LTP) (Sasi et al., 2017).
children (Cho et al., 2017). Yoga has also been shown BDNF activated signaling cascades involve, mainly
to improve levels of BDNF in MDD (Naveen et al., its receptor, the receptor tyrosine kinase (TrkB),
2016). Our study further confirmed that in MDD sub- and mechanistic target of rapamycin (mTOR). Evi-
jects 12 weeks of YMLI could significantly increase dence suggests that vagal nerve stimulation rapidly
activates TrkB in rat brain. Yoga components in training promotes functional neuroplastic changes,
YMLI might improve parasympathetic activity and and implicate decoupling of the amygdala and
cardiovagal tone (Streeter et al., 2012). mTOR is a subgenual anterior cingulate cortex (sgACC) as
regulator for the initiation of protein translation and a potential neurobiological mechanism underlying
synthesis. Elevated mTOR signaling promotes the mindfulness training intervention effects. Naveen et
synthesis of synaptic proteins that are necessary for al. (2016) have shown that cortisol reduction in MDD
synapse formation and maturation (Abelaira et al., by yoga correlated with an increase of BDNF levels
2014; N. Li et al., 2010). The mTOR signaling path- in the blood. Our study confirms that YMLI decreases
way may also be activated by N-methyl-d-aspartate cortisol level and improve MBCs that regulate neu-
(NMDA) receptor, and dopamine receptor-mediated roplasticity in MDD. Also, findings from our study
signaling (Duman & Voleti, 2012). The mTOR- show that YMLI mediated decrease in cortisol has a
dependent translational cascade in synaptic plasticity significant impact on increasing BDNF and reducing
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may be the final pathway that represents a rapid- depression severity. Previous studies have indicated
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acting and long-lasting onset of therapeutic benefits, that increased cortisol depress activity-dependent
including YMLI. Bekker et al. (2014) have suggested expression of BDNF mRNA in hippocampal neu-
that regulation of gene expressions including BDNF rons (Cosi et al., 1993; Smith et al., 1995). Therefore,
is important for the actions of active interventions decrease in cortisol after YMLI may increase BDNF
like mindfulness. Improved mind-communicative and enhance BDNF mediated neuroplasticity. Cellu-
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and cellular health biomarkers may have a signifi- lar recovery may involve multiple regulatory factors
cant role in optimizing gene expressions, including like the eukaryotic translation initiation factor 2 alpha
BDNF. (eIF2␣) that converge on the regulation of adaptive
pathways including integrated stress response (ISR)
4.2. YMLI improve mind-body communications (Pakos-Zebrucka et al., 2016), which drive the sig-
d
(MBCs) to regulate neuroplasticity naling toward cell survival and longevity.
The immune system is an essential component of
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The most significant dysregulation of MBCs the physiological stress-sensing pathways and closely
for brain pathology in MDD includes exaggerated interacts with the body’s primary integrative MBC
stress response, immune hyperactivity (Pribiag & systems, including HPA axis, in mutually regulatory
Stellwagen, 2014), and abnormalities in adipos- feed-forward and feedback loops. Previous research
c
ity, vascularity, and sexuality (Verhoeven et al., has documented the neuroimmunological mecha-
2014). These dysregulations in MBCs have a detri- nisms of peripheral immune dysfunction in MDD,
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mental impact on the CNS, and damage neuropil and have shown that these routes converge in the
structure and function leading to deficits of neu- CNS to alter molecular programmes, neurogenesis,
roplasticity. The HPA axis is the most common and plasticity (Hodes et al., 2015). Frodl et al. have
biological system for MBCs in MDD (Holsboer reported that high IL-6 levels are associated with
or
& Ising, 2010; Schatzberg, 2015) and alterations increased cortisol and reduced hippocampal volumes
in it are associated with impaired higher mental in MDD (Frodl et al., 2012). A systematic review
functions (Hinkelmann et al., 2009). Meta-analyses of gene expression changes by Buric et al. (2017)
concluded in the past have confirmed that patients indicate that MBI practices are linked to downregu-
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with MDD have increased cortisol levels (Stetler & lation of nuclear factor kappa B (NF κB) pathway,
Miller, 2011). Higher cortisol levels are associated an effect opposite to that of chronic stress on gene
with reductions in hippocampus volume (Colla et expression. Meditation results in a decrease in inflam-
al., 2007), and decreasing cortisol levels reverses mation as evident from the reduction in levels of
this change (Vythilingam et al., 2004). Increased inflammatory marker IL-6 and increases neuroplas-
cortisol is known to suppress BDNF secretion in ticity, as shown in a study using imaging (Creswell
the brain by repressing glucocorticoid receptors et al.). Our findings of a decrease in IL-6 after YMLI
(Chen et al., 2017; McEwen et al., 2016) and con- suggests that MBI practices may lead to a reduced
tribute to neurodegeneration. Findings across groups risk of inflammation-related neuropathology (Buric
in our study support the association of increased et al., 2017). Our present study is the first to show
cortisol with reductions in BDNF and increase in that 12 weeks of YMLI could reduce the IL-6 lev-
depression severity. A study by Taren et al. (Taren els in MDD, indicating that YMLI practice is an
et al., 2015) indicates that mindfulness meditation efficient way for reducing neuroinflammation and
pathological changes in the brain associated with Among the factors which promote longevity, nutri-
MDD. tion and energy sensing pathways are important, and
DHEA and its sulfated derivative, DHEAS, sirtuin 1 play a prominent role, in association with
are cholesterol-derived steroids synthesized in the other factors. Sirtuin 1 (SIRT1), a member of mam-
adrenal glands and de novo in neurons and glia. malian class III histone deacetylases, and a nutrient
DHEAS acts as a GABA(A) receptor noncompeti- and energy sensor (Toorie et al., 2016), has been a
tive antagonist and a positive allosteric modulator at target for interventions in longevity and aging-related
the NMDA receptor (Genud et al., 2009; Kimonides diseases. It is known to block neuropathology, prevent
et al., 1998). It has neuroprotective, antioxidant, neuronal cell death (Cunha-Santos et al., 2016; Guida
and anti-inflammatory properties (Maninger et al., et al., 2015; Nimmagadda et al., 2013), and promote
2009), and appears to be dysregulated in MDD synaptic plasticity (Gao et al., 2010). Recent evidence
(Wong et al., 2011). Previous studies have shown suggests that caloric restriction and resveratrol could
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that DHEA administration in MDD patients reported increase circulating sirtuin 1 levels (Guarente, 2013;
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a significant reduction in depressive symptomatol- Xu et al., 2014). Our study is the first to document
ogy (Schmidt et al., 2005). In a review, Sripada et an increase in sirtuin 1 levels independent of caloric
al., (Sripada et al., 2013) have illustrated that DHEA restriction after YMLI in MDD. Our findings also
enhances emotion regulation neurocircuits and mod- suggest that sirtuin 1 contributes significantly to the
ulates memory for emotional stimuli. In the present association of BDNF with BDI-II scores. A study
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study patients receiving YMLI showed increased in rats has reported that rehabilitation training and
DHEAS levels. Postmortem studies using the brain of resveratrol improve the recovery of neurological and
MDD patients indicate a close relationship between motor function after cerebral ischemic injury through
DHEA and BDNF-TrkB pathways (Qi et al.). DHEA the sirt1 signaling Pathway (Shi et al., 2016). Poten-
has also been shown to increase neuron survival by tial underlying molecular mechanisms for decrease
d
modulation of the mTOR signaling (T. Chen et al., in MDD severity by increased sirtuin 1 include: (1)
2017). Therefore, increased DHEAS after YMLI may increasing cell survival and neurogenesis through
te
increase BDNF mediated neuroplasticity by activat- mTOR signaling (Guo et al., 2011), (2) promoting
ing mTOR pathways. Increased DHEAS after YMLI synaptic plasticity by increasing BDNF transcription,
may also decrease depression severity by decreasing mediated by inhibition of miR-134 expression that
heightened brain excitability of MDD (Pennisi et al., inhibit binding of cAMP response element-binding
c
2016), since DHEAS can inhibit glutamate-induced protein (CREB) to several BDNF promoters, (3) reg-
excitotoxicity (T. Chen et al., 2017; Dong et al., ulating circadian rhythm mediated by inhibiting the
re
2009) and modulate the inhibitory neurotransmitter central circadian timer protein CLOCK, a histone
GABA (Genud et al., 2009). Goldman and Glei have acetyltransferase (Nakahata et al., 2009).
reported that lower levels of DHEAS increase depres- The improved mind-body communicative
sive symptoms in men, which may contribute to biomarkers constitute the reversal of senescent
or
increased baseline severity as seen in our study (Gold- secretory phenotype of cells, both in the CNS
man & Glei, 2007). Although not significant, women and peripheral organ systems. Since, secretory
tended to show higher reductions in depression sever- phenotype from somatic cells provides regulatory
ity. This may be due to transitory and fluctuating sex feedback to the brain (Tchkonia et al., 2013),
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hormone levels in the brain that induce the contin- improved biomarkers after YMLI may mediate to
uous functional adaptation of the CNS throughout optimize the vicious cycle of regulation between
the lifespan, particularly in females (Juraska et al., mind and body and contribute to decreasing in
2013; Nugent et al., 2012). It has been observed MDD neuropathology. Crosstalk between regulatory
that neurogenesis in the dentate gyrus is higher feedback pathways and neurocircuits in the brain
in female than in males, probably because of the not only play a role in pathogenesis but also drive
variations in gonadal hormones (Duarte-Guterman the progression of depression, which may contribute
et al., 2015). Evidence suggests that estradiol (E2) to non-responsiveness to current antidepressant
and/or progesterone (P4) promote neurogenesis and therapies. Regulated mind-body communications
neurological functions under different brain insults may lead to the minimization of the adverse effects
and diseases (Z. Li et al., 2012; Zheng et al., of these cross-talks to provide improved clinical
2013), and also protect against neurodegenerative outcomes. Our present study suggests that, in MDD,
diseases. 12 weeks of YMLI could improve MBCs, decrease
pathobiology of MDD and contribute to enhanced diseases (Camiletti-Moiron et al., 2013; Garcı́a-Mesa
neuroplasticity and decrease in depression severity. et al., 2016; Huang et al., 2015; Teixeira de Lemos
et al., 2012; Vinetti et al., 2015). Recent evidence
4.3. YMLI improves cellular health to promote has confirmed that yoga and meditation could re-
neuroplasticity establish oxidative eustress in apparently healthy
people by increasing total antioxidant capacity,
Cellular health, of both CNS and peripheral reducing inflammation and improvement in mito-
organ systems, and its long-term maintenance across chondrial DNA integrity (Tolahunase et al., 2017).
the lifespan, is fundamental to achieve optimum Findings from our study show that MDD therapy with
neuroplasticity. This can ensure continued remis- YMLI contributes significantly to achieve oxidative
sion in MDD, prevent complications, and improve eustress and decrease DNA damage. The pathophys-
somatic health. Achieving and maintaining opti- iological relationships between oxidative stress and
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mum cellular health depend on oxidative eustress, depression, and the potential benefits of both passive
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genomic stability, chromosomal integrity and telom- and active interventions to achieve optimum oxida-
ere length maintenance. Biomarkers of cellular health tive eustress deserve further research.
are rapidly being accepted as surrogate markers of Several studies and meta-analyses have reported
MDD and other chronic lifestyle diseases. Deviation that a reduction in telomere length systemically,
from oxidative eustress is associated with macro- is associated with stressed individuals and MDD
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molecular damage, telomere attrition (Szebeni et al., (Lin et al., 2016; Lopizzo et al., 2017; Schutte &
2014), epigenetic modifications, and altered gene Malouff, 2015; Wolkowitz et al., 2011). Recent stud-
expressions. It is strongly associated with MDD ies have also documented dysregulation in telomere
pathobiology (Black et al., 2015), including altered metabolism within the brain of a rat model of depres-
neuroprotection, neurogenesis, and neuroplasticity in sion (Wei et al., 2015) and postmortem brain of
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the brain (Vaváková et al., 2015). HPA hyperactiv- MDD patients (Szebeni et al., 2014). Research evi-
ity predisposes to increased cellular oxidative stress dence suggests that regular practitioners of yoga
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(Spiers et al., 2015). Within the CNS, in comparison have increased telomere length compared to con-
to glial cells, neurons are more vulnerable to oxida- trols (Krishna et al., 2015), and yoga practice by
tive stress due to the relatively poor expression of apparently healthy individuals can increase telom-
endogenous antioxidants. Szebeni et al. (2017) have ere metabolism and promote longevity by slowing
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even documented the elevated DNA oxidation and the rate of aging (Tolahunase et al., 2017).The
DNA repair enzyme expression in brain white matter main factor that causes rapid attrition of telom-
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in MDD. Our study suggests that increase in oxida- eres is oxidative stress, and YMLI reduces oxidative
tive stress may significantly impact BDNF levels stress and inflammation and thereby aids in telomere
and depression severity in MDD. Therefore, achiev- length maintenance and promotes genome stability
ing optimum oxidative eustress, even under extremes and maintenance of chromosomal integrity. Recent
or
of stress associated with lifestyle and environmen- studies have also identified the possible molecular
tal challenges, is a highly sensitive task. Previous mechanisms of increase in telomere protection, after
studies from our laboratory have documented that exercise (Ludlow et al., 2017). Telomerase activity is
YMLI improves mitochondrial integrity as evident known to mediate the cell survival, promoting actions
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from increased COX activity. This aids in reduc- of BDNF (Fu et al., 2002). Findings from our study
ing supraphysiological free radical levels by the not only show a significant increase in telomerase
electron transport chain during oxidative phosphory- activity in the yoga group but also to predict BDNF
lation. A range of strategies is adopted for reducing mediated reduction in depression severity. While
or preventing the oxidative stress (Poljsak, 2011). A yoga group showed an increase in telomere length
meta-analysis by Liu et al. (2015) reported that the compared to control group, findings were not signifi-
levels of antioxidant are increased, and the levels of cant, but a reduction in oxidative stress levels prevents
oxidative damage products are decreased after antide- further attrition of telomere length. Improvement in
pressant medication. While passive interventions like MBC and cellular health suggest that, unlike passive
drugs and anti-oxidants can modify oxidative stress, drug treatments and mind- or body-only interven-
clinical benefits are suboptimal. Active interventions, YMLI improve cellular health and longevity in
tions like regular physical exercise are also beneficial both brain and peripheral organ systems. This might
in reducing oxidative stress in chronic lifestyle be one of the mechanisms through which yoga- and
meditation-based interventions exert their effects on tive when practiced with all the classical components
neuroplasticity. However, further studies are required included, and as a way of life. Patients receive medita-
to confirm these findings. Molecular mechanisms tion (mind intervention, the seventh limb), only after
underlying YMLI mediated reduction in depres- both the body and the mind are conditioned, in a step-
sion severity might involve epigenetic regulation. wise manner, so that brain is ready for the molding
Several studies have demonstrated the epigenetic effects of this intervention. Āsana s (third limb) and
modifications in MDD pathobiology, chiefly due to Prā āyāma (fourth limb) provide benefits for somatic
OS (Klengel & Binder, 2013, 2015). For example, molding, independently too, like in exercise interven-
DNA demethylation of FKBP5 leads to its increased tions. Moreover, YMLI extends further to Samādhi
expression in response to stress, which in turn leads (the eighth limb), the final state of self-awareness
to glucocorticoid receptor resistance and increased (also termed Kaivalya), where the practitioner realize
levels of cortisol. Na et al. (2016) have shown that total freedom and independence from any stimulation
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higher levels of BDNF promoter methylation have a whatsoever, both external and internal. Achieving
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close association with the reduced cortical thickness such a state involve mental processes like deliber-
among patients with MDD. Improved biomarkers of ation, reflection, and bliss that involve complex and
neuroplasticity after YMLI, may reverse these epi- dynamic higher functional neural networks. Unlike
genetic modifications, and contribute to decrease in in mind-interventions (MIs), where cognitive areas of
pathology and increase in clinical outcomes in MDD. the brain are mainly targeted, in MBIs (yoga), regions
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and networks of the brain regulating somatic and veg-
4.4. YMLI as a comprehensive MBI in MDD etative functions (hypothalamus), biological rhythms
(pineal gland), emotion (hippocampus, amygdala),
Research has shown that both the passive and active cognition (PFC), and social behavior (higher func-
treatments can modify neuroplasticity, although, the tional ‘comport’ neural networks), receive improved
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nature of biological and clinical impact vary (Dale regulatory feedbacks from the peripheral organ sys-
et al., 2015). Current, first-line pharmacotherapy, tems, either directly, or through other regions of the
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is passive, and the therapeutic effect is based on CNS regulating them, like thalamus, and cerebel-
increasing the levels of specific monoamines in the lum. Studies from our laboratory have documented
synaptic clefts. The regions where this increase will an increase in serotonin and melatonin levels post
occur does depend on the type of monoamine tar- yoga intervention (outside the purview of this paper).
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geted, and the neural circuitry of that monoamine. Expression of clinical symptoms in adults with
Serotonin is the target of the most commonly used MDD is associated with pathology that may result
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anti-depressants, and its circuitry may not be reg- from cumulative changes during decades of brain
ulating all the large-scale neural networks. While development and structural and functional modi-
antidepressant drug treatments have been linked to fications in the brain due to environmental and
a bottom-up modulation of neural networks related lifestyle factors. It is widely believed that devel-
or
to cognition and emotion by increasing monoamine opmental alterations of neural networks may be
levels, mind-only active interventions like, cognitive difficult to restore by pharmacological interven-
behavioral therapy (CBT), have been implicated in tion. Active MBIs like YMLI, may, however, refine
a top-down control of these neural networks. Also, the neural circuits formed during development, and
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evidence shows that physical exercise can also pro- enable functional modulation of synapses to restore
vide remissions or decrease the severity in MDD, neural network function. YMLI increases biomark-
although the extent of its effectiveness is unknown. ers of neuroplasticity, at the level of the brain,
Yoga, a MBI having both psychological and physi- mind-body communications, and cellular health,
cal components, will have benefits beyond additive improves the mitochondrial and nuclear integrity and
effects from psychotherapy and physical exercise. improves COX activity. Therefore, YMLI may not
The reason being, in yoga, as practiced in YMLI, is only help to decrease severity in MDD but also
based on the yoga sutras (principles) of Patanjali hav- offer hope for complete remission from MDD that
ing eight limbs (Yama, Niyama, Āsana, Prā āyāma, result from heterogeneous biological mechanisms.
Pratyāhāra, Dhāra ā, Dhyāna, and Samādhi). Āsana Possible epistasis between the genes encoding func-
(physical postures), Prā āyāma (breathing exer- tions of the brain, mind-body communications, and
cises), and Dhyāna (meditation) are relatively more cellular health, may be responsible for modifying
emphasized in modern times; yoga is most effec- pathobiology and progression of MDD by YMLI
that may not be possible due to the effect on one 5. Conclusions

aspect of MDD pathology alone (like a gene, region
or process), as occurs with pharmacological and other Short term Yoga- and meditation- based lifestyle
passive interventions. Therefore, benefits from YMLI intervention in MDD decreased clinical severity in
is more powerful, since the effects of interactions may association with an increase in neuroplasticity, by
be beneficial for all endophenotypes of MDD, unlike significantly improving brain physiology, MBC, and
in pharmacotherapy or psychotherapy, where spe- cellular health. Our study suggests that increased
cific endophenotypes show responses or remissions. neuroplasticity may be part of underlying biologic
These phenomena that empower neuroplasticity to mechanisms to decrease clinical severity in MDD.
CNS through YMLI need to be further explored Moreover, it may prevent complications that are
using modern technologies and methodologies. As related to drug therapy, reduce relapses and provide
documented in our previous studies, improvement long-lasting clinical remission. It may also increase
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in mitochondrial and nuclear DNA integrity and cognitive reserve to decrease the risk of dementia and
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improvement in COX activity after YMLI, aids in increase functional reserves to decrease risk for age-
meeting the energy demands of a tissue with a high related chronic medical conditions. Thus it can be
metabolic rate. considered as a significant component of integrative
To the best of our knowledge, the present study health strategy in the prevention and management of
is the first RCT of yoga studying its impact on cel- MDD and increase both healthspan and lifespan.
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lular health and mind-body communicative factors
on neuroplasticity and depression severity in cases
with major depressive disorder. Exploring pathobi- Competing interests
ology of MDD is essential in the investigation of
yoga as a potential therapy for major depression. The authors have declared that no competing inter-
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Although the sample size was small, findings from ests exist.
our study contribute RCT data regarding clinical ben-
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efits of yoga and the potential biological mechanisms
in MDD. Our trial is distinct from many previous Acknowledgments
yoga trials by including all limbs of classical yoga
based on the yoga sutras (principles) of Patanjali. We thank the participants for their dedicated par-
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Such protocols facilitate the expansion of therapeutic ticipation in the study. Authors sincerely thank yoga
options that can provide not only optimum remis- instructors Amit Tomar, Sudheer Chaudhary, and
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sion but also promote long-term positive health and Sneha. This study was supported by the ICMR (Grant
longevity. YMLI is a profound science of wellbeing number: 54/3/GER2014NCD11).
which is designed in line with ‘the family traditions’
passed on through generations in Indian society. It
or
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Restorative Neurology and Neuroscience xx (20xx) x–xx 1

Original Research Article

Yoga- and meditation-based lifestyle

∗ Corresponding author: Dr Rima DADA, M.D., Ph.D. (Genet-

ers of neuroplasticity in MDD patients on routine

research randomizer (https://www.randomizer.org/), ROS detection was done by chemiluminescence

Table 2 BDI-II score [–5.83 (–7.27, –4.39), p < 0. 001] and

Fig. 1. CONSORT flow chart of the study.

produced similar results. The regression model pre-

P < 0.05) were associated with increased BDI-II

group in comparison to control group. Yoga group

Telomerase Activity –0.044 0.018 –0.296∗ –2.457

Mind-body communicative biomarkers

0.065 0.057 0.298 1.144

Telomerase Activity 0.004 0.046 0.020 0.086

that may not be possible due to the effect on one 5. Conclusions

can, therefore, be easily integrated as a way of life References

tuin deacetylase gene expression in patients with a mood

K.J. (2012). Effects of yoga on mental and physical health:

meditation with reduced interleukin-6: A randomized con-

and Science in Sports, 23(4), e202-212. doi: 10.1111/sms.

Cunha-Santos, J., Duarte-Neves, J., Carmona, V., Guarente,

Jesko, H., Wencel, P., Strosznajder, R.P., & Strosznajder, J.B.

doi: 10.1007/s11064-016-2110-y depression. PloS One, 10(10), e0138904. doi: 10.1371/jour-

programming across the lifespan. Hormone and Metabolic

1112-1120. doi: 10.1016/S1470-2045(13)70366-8

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