Yoga, Meditation and Mind-Body Health: Increased BDNF, Cortisol Awakening Response, and Altered Inflammatory Marker Expression after a 3-Month Yoga and Meditation Retreat

“The HPA axis is an important neuroendocrine system whose activation underlies the stress response (de Kloet et al., 2005).”

“…that acts on neurons of the central and peripheral nervous system, supports the survival of existing neurons, and encourages the growth and differentiation of new neurons and synapses primarily through its action at the TrkB receptor of neurons (Acheson et al., 1995; Huang and Reichardt, 2001).”

“Chronic inflammatory states can be triggered through psychosocial stress (Steptoe et al., 2007; Miller et al., 2009; Irwin and Cole, 2011), and psychosomatic interventions like meditative practices that invoke stress-reduction mechanisms and psychophysiological self-regulation have demonstrated…”

“Lastly, given the clear relationship between increased stress and decreases in BDNF signaling (Duman and Monteggia, 2006; Schmidt and Duman, 2007), other central mechanisms related to the impact of meditative practice on decreasing stressful responding to daily life stressors may play an important…”

“Studies in mice have demonstrated associations between the gut microbiota and BDNF in the regulation of brain physiology, behavior, and memory (Diaz Heijtz et al., 2011).”

“Some of these cytokines, such as IL-6, can induce both pro- and anti-inflammatory effects thus adding an additional layer of complexity (Scheller et al., 2011).”

“…modulations of frontal brain circuitry supporting the act of meditative practice (Tang and Posner, 2009; Brewer et al., 2011; Lutz et al., 2015; Tang et al., 2015), it is quite possible that the meditative components of this intensive retreat engaged neuroplastic brain mechanisms in a manner…”

“Decades of research have linked meditation-based practices to positive psychological and health outcomes in both clinical and nonclinical populations (Grossman et al., 2004; Cahn and Polich, 2006; Rubia, 2009; Chiesa and Serretti, 2010; Keng et al., 2011; Davidson and McEwen, 2012).”

“…that pro-inflammatory bodily states are associated with a propensity towards mental disorders such as depression and anxiety (Miller et al., 2009; Slavich and Irwin, 2014; Furtado and Katzman, 2015; Strawbridge et al., 2015) as well as an array of chronic medical illnesses (Aggarwal et al.,…”

“Psychometric questionnaires included the Brief Symptom Inventory-18 (BSI-18; Derogatis, 2000), the Freiburg Mindfulness Inventory (Walach et al., 2006), and the Tellegen Absorption Scale (Tellegen and Atkinson, 1974).”

“…although IL-6 is associated with pro-inflammatory pathways when stimulated through psychological stress, fever, or the acute phase response, IL-6 is also a myokine known to have anti-inflammatory effects when stimulated through exercise (Barton, 1997; Tilg et al., 1997; Opal and DePalo, 2000).”

“…towards the possibility that sustained engagement with meditative practices has both salubrious psychological and neurophysiological benefits (Cahn and Polich, 2006; Dahl et al., 2015; Tang et al., 2015; Luders and Cherbuin, 2016) and positively enhances biological functioning through both…”

“BDNF is a key neurotrophin that promotes development, survival and plasticity of neurons in the central and peripheral nervous systems (Huang and Reichardt, 2001; Binder and Scharfman, 2004).”

“Psychometric questionnaires included the Brief Symptom Inventory-18 (BSI-18; Derogatis, 2000), the Freiburg Mindfulness Inventory (Walach et al., 2006), and the Tellegen Absorption Scale (Tellegen and Atkinson, 1974).”

“…engagement and associated robust modulations of frontal brain circuitry supporting the act of meditative practice (Tang and Posner, 2009; Brewer et al., 2011; Lutz et al., 2015; Tang et al., 2015), it is quite possible that the meditative components of this intensive retreat engaged…”

“Decades of research have linked meditation-based practices to positive psychological and health outcomes in both clinical and nonclinical populations (Grossman et al., 2004; Cahn and Polich, 2006; Rubia, 2009; Chiesa and Serretti, 2010; Keng et al., 2011; Davidson and McEwen, 2012).”

“Likely related to its ability to cross the blood-brain barrier, peripheral serum levels of BDNF are correlated with cerebrospinal fluid levels (Pan et al., 1998).”

“Decreased BDNF levels have been associated with psychiatric and neurological disorders including anxiety, depression and Alzheimer’s disease (Phillips et al., 1991; Chen et al., 2006; Bocchio-Chiavetto et al., 2010), as well as emotional exhaustion and burnout (Onen Sertoz et al., 2008).”

“…states are associated with a propensity towards mental disorders such as depression and anxiety (Miller et al., 2009; Slavich and Irwin, 2014; Furtado and Katzman, 2015; Strawbridge et al., 2015) as well as an array of chronic medical illnesses (Aggarwal et al., 2006; Swardfager et al., 2010).”

“Chronic inflammatory states can be triggered through psychosocial stress (Steptoe et al., 2007; Miller et al., 2009; Irwin and Cole, 2011), and psychosomatic interventions like meditative practices that invoke stress-reduction mechanisms and psychophysiological self-regulation have demonstrated…”

“The increased CAR we report here is likely related to increases in morning wakefulness and stress resilience (Fries et al., 2009; Clow et al., 2010a,b).”

“…states are associated with a propensity towards mental disorders such as depression and anxiety (Miller et al., 2009; Slavich and Irwin, 2014; Furtado and Katzman, 2015; Strawbridge et al., 2015) as well as an array of chronic medical illnesses (Aggarwal et al., 2006; Swardfager et al., 2010).”

“…cytokine IL-10, produced by Th2 cells, has been shown to result in the inhibition in the synthesis of pro-inflammatory cytokines generally (Mosser and Zhang, 2008), including TNFα, IL-1β, IL-12 and IFNγ (Zheng et al., 1996; Aste-Amezaga et al., Frontiers in Human Neuroscience |…”

“…also an important and separate relationship between the homeostatic fitness of the autonomic nervous system and robust circadian variations in cortisol levels, with sympathetic hyperactivity demonstrating a tendency to reduce the circadian variability of cortisol levels (Chida and Steptoe, 2009).”

“Physical exercise and environment learning have been clearly demonstrated to exert hippocampal plasticity through upregulating BDNF signaling (Vivar et al., 2013; Voss et al., 2013).”

“For example, acute exercise is known to increase the expression of both pro-inflammatory IL-1β and TNF-α as well as anti-inflammatory IL-6 and IL-10 (Northoff et al., 1994; Ostrowski et al., 1999).”

“Chronic inflammatory states can be triggered through psychosocial stress (Steptoe et al., 2007; Miller et al., 2009; Irwin and Cole, 2011), and psychosomatic interventions like meditative practices that invoke stress-reduction mechanisms and psychophysiological self-regulation have demonstrated…”

“Decades of research have linked meditation-based practices to positive psychological and health outcomes in both clinical and nonclinical populations (Grossman et al., 2004; Cahn and Polich, 2006; Rubia, 2009; Chiesa and Serretti, 2010; Keng et al., 2011; Davidson and McEwen, 2012).”

“Given that previous work demonstrating generally equivalent plasma BDNF levels inmen and women (Lommatzsch et al., 2005), we take the finding of greater BDNF levels in women than men of this study to be related to non-random sampling of the general population.”

“Chronic inflammatory states can be triggered through psychosocial stress (Steptoe et al., 2007; Miller et al., 2009; Irwin and Cole, 2011), and psychosomatic interventions like meditative practices that invoke stress-reduction mechanisms and psychophysiological self-regulation have demonstrated…”

“…that sustained engagement with meditative practices has both salubrious psychological and neurophysiological benefits (Cahn and Polich, 2006; Dahl et al., 2015; Tang et al., 2015; Luders and Cherbuin, 2016) and positively enhances biological functioning through both hypothalamic pituitary…”

“, 2014) as well as anti-depressant effects (RussoNeustadt et al., 2000; Warner-Schmidt and Duman, 2006; Sen et al., 2008).”

“While some have reported an overall decrease in daily cortisol secretion followingmindfulness practice (Carlson et al., 2003, 2007;WitekJanusek et al., 2008), others have found no change (Robinson et al., 2003; Galantino et al., 2005; Klatt et al., 2009).”

“…that acts on neurons of the central and peripheral nervous system, supports the survival of existing neurons, and encourages the growth and differentiation of new neurons and synapses primarily through its action at the TrkB receptor of neurons (Acheson et al., 1995; Huang and Reichardt, 2001).”

“Decades of research have linked meditation-based practices to positive psychological and health outcomes in both clinical and nonclinical populations (Grossman et al., 2004; Cahn and Polich, 2006; Rubia, 2009; Chiesa and Serretti, 2010; Keng et al., 2011; Davidson and McEwen, 2012).”

“, 2005); however, acute inflammatory responses are also adaptive, so the general decrease of pro-inflammatory (and increase in anti-inflammatory) immune mediators is not always a clear marker of health and wellness, and instead a healthy homeostatic balance between pro- and anti-inflammatory signaling is most adaptive…”

“First, given the significant and growing evidence for the highly active attentional engagement and associated robust modulations of frontal brain circuitry supporting the act of meditative practice (Tang and Posner, 2009; Brewer et al., 2011; Lutz et al., 2015; Tang et al., 2015), it is quite possible that the meditat…”

“While some have reported an overall decrease in daily cortisol secretion followingmindfulness practice (Carlson et al., 2003, 2007;WitekJanusek et al., 2008), others have found no change (Robinson et al., 2003; Galantino et al., 2005; Klatt et al., 2009).”

“…although IL-6 is associated with pro-inflammatory pathways when stimulated through psychological stress, fever, or the acute phase response, IL-6 is also a myokine known to have anti-inflammatory effects when stimulated through exercise (Barton, 1997; Tilg et al., 1997; Opal and DePalo, 2000).”

“…states are associated with a propensity towards mental disorders such as depression and anxiety (Miller et al., 2009; Slavich and Irwin, 2014; Furtado and Katzman, 2015; Strawbridge et al., 2015) as well as an array of chronic medical illnesses (Aggarwal et al., 2006; Swardfager et al., 2010).”

“Lastly, given the clear relationship between increased stress and decreases in BDNF signaling (Duman and Monteggia, 2006; Schmidt and Duman, 2007), other central mechanisms related to the impact of meditative practice on decreasing stressful responding to daily life stressors may play an important…”

“Given accumulating evidence that yoga and meditative practices modulate inflammatory and HPA activity (Jevning et al., 1978; Brown and Gerbarg, 2005; Kiecolt-Glaser et al., 2010; Bower and Irwin, 2015) and the possibility that yoga and meditative practices may positively impact BDNF levels as a…”

“For example, Pullen et al. (2008) showed decreases in IL-6, while Creswell et al. (2012) reported no change in IL-6; Rosenkranz et al. (2013) showed that more meditation practice was associated with lower TNF-α, while Black et al. (2013) reported an increase in TNF-α mRNA expression after yogic…”

“Accumulating evidence links excessive adrenocortical activity and elevated basal cortisol levels to the progression of psychiatric and other medical illness (Brown et al., 2004; de Kloet et al., 2005; Zannas et al., 2015).”

“…active attentional engagement and associated robust modulations of frontal brain circuitry supporting the act of meditative practice (Tang and Posner, 2009; Brewer et al., 2011; Lutz et al., 2015; Tang et al., 2015), it is quite possible that the meditative components of this intensive…”

“…practice component of the retreat, such meditationrelated BDNF signaling may be a partial explanation for the repeated findings of increased hippocampal volumes due to meditative practice in both short and long term studies (Hölzel et al., 2008, 2011; Luders et al., 2009; Gotink et al., 2016).”

“Of note, a generally observed cytokine response to stress andmediated through glucocorticoids includes a reduction of the T helper 1 cell (Th1)-mediated production of pro-inflammatory IFN-γ, TNF-α and IL-12 and an activation of T helper 2 cell (Th2)-mediated production of IL-10.”

“…practice was associated with lower TNF-α, while Black et al. (2013) reported an increase in TNF-α mRNA expression after yogic meditation; and Witek-Janusek et al. (2008) reported increases in IFN-γ activity in breast cancer patients, while Carlson et al. (2003) reported a decrease in a…”

“…implicated as a mediator of the positive impact of both physical exercise and cognitive engagement on brain fitness and enhanced neurogenesis, learning, and memory (Huang et al., 2014) as well as anti-depressant effects (RussoNeustadt et al., 2000; Warner-Schmidt and Duman, 2006; Sen et al., 2008).”

“Moreover, a large body of evidence has demonstrated that the negative impact of inflammation on neurogenesis might be triggered through pro-inflammatory cytokine-induced reductions in BDNF expression/signaling (Calabrese et al., 2014).”

“…practice component of the retreat, such meditationrelated BDNF signaling may be a partial explanation for the repeated findings of increased hippocampal volumes due to meditative practice in both short and long term studies (Hölzel et al., 2008, 2011; Luders et al., 2009; Gotink et al., 2016).”

“Decreased BDNF levels have been associated with psychiatric and neurological disorders including anxiety, depression and Alzheimer’s disease (Phillips et al., 1991; Chen et al., 2006; Bocchio-Chiavetto et al., 2010), as well as emotional exhaustion and burnout (Onen Sertoz et al., 2008).”

“…yoga and meditative practices modulate inflammatory and HPA activity (Jevning et al., 1978; Brown and Gerbarg, 2005; Kiecolt-Glaser et al., 2010; Bower and Irwin, 2015) and the possibility that yoga and meditative practices may positively impact BDNF levels as a mechanism towards salubrious…”

“Later effects of stress can include induction of IL-1β, IL-8 and TNF-α (Elenkov et al., 2005; Calcagni and Elenkov, 2006).”

“Extensive previous work has demonstrated increased circulating BDNF levels due to both acute and chronic aerobic exercise regimes (Brunelli et al., 2012; Dinoff et al., 2016).”

“Physical exercise and environment learning have been clearly demonstrated to exert hippocampal plasticity through upregulating BDNF signaling (Vivar et al., 2013; Voss et al., 2013).”

“While some have reported an overall decrease in daily cortisol secretion followingmindfulness practice (Carlson et al., 2003, 2007;WitekJanusek et al., 2008), others have found no change (Robinson et al., 2003; Galantino et al., 2005; Klatt et al., 2009).”

“…our participants scored low on anxiety and depression symptomatology, and when compared to previous literature in healthy normal populations (Kleiner et al., 2013; Krishnan et al., 2014) our levels were decreased in amplitude across the various cytokines obtained, likely indicating that in…”

“BDNF is a well-described neurotrophic factor of the neurotrophin gene family that acts on neurons of the central and peripheral nervous system, supports the survival of existing neurons, and encourages the growth and differentiation of new neurons and synapses primarily through its action at the TrkB receptor of neuro…”

“…practice component of the retreat, such meditationrelated BDNF signaling may be a partial explanation for the repeated findings of increased hippocampal volumes due to meditative practice in both short and long term studies (Hölzel et al., 2008, 2011; Luders et al., 2009; Gotink et al., 2016).”

“Given accumulating evidence that yoga and meditative practices modulate inflammatory and HPA activity (Jevning et al., 1978; Brown and Gerbarg, 2005; Kiecolt-Glaser et al., 2010; Bower and Irwin, 2015) and the possibility that yoga and meditative practices may positively impact BDNF levels as a…”

“Ameta-analysis of randomized controlled trials of mind-body therapies including yoga, meditation and tai-chi revealed small but not statistically significant decreases in IL-6 and TNF-α following such interventions (Morgan et al., 2014), and a later descriptive review of this literature highlighted the inconsistent na…”

“Decades of research have linked meditation-based practices to positive psychological and health outcomes in both clinical and nonclinical populations (Grossman et al., 2004; Cahn and Polich, 2006; Rubia, 2009; Chiesa and Serretti, 2010; Keng et al., 2011; Davidson and McEwen, 2012).”

“…although IL-6 is associated with pro-inflammatory pathways when stimulated through psychological stress, fever, or the acute phase response, IL-6 is also a myokine known to have anti-inflammatory effects when stimulated through exercise (Barton, 1997; Tilg et al., 1997; Opal and DePalo, 2000).”

“…et al. (2012) reported no change in IL-6; Rosenkranz et al. (2013) showed that more meditation practice was associated with lower TNF-α, while Black et al. (2013) reported an increase in TNF-α mRNA expression after yogic meditation; and Witek-Janusek et al. (2008) reported increases in…”

“Matousek et al. (2010) reasonably suggest that such discrepancies might be attributed to methodological differences, such as sample size and population characteristics.”

“Of note, a generally observed cytokine response to stress andmediated through glucocorticoids includes a reduction of the T helper 1 cell (Th1)-mediated production of pro-inflammatory IFN-γ, TNF-α and IL-12 and an activation of T helper 2 cell (Th2)-mediated production of IL-10.”

“Accumulating evidence links excessive adrenocortical activity and elevated basal cortisol levels to the progression of psychiatric and other medical illness (Brown et al., 2004; de Kloet et al., 2005; Zannas et al., 2015).”

“While some have reported an overall decrease in daily cortisol secretion followingmindfulness practice (Carlson et al., 2003, 2007;WitekJanusek et al., 2008), others have found no change (Robinson et al., 2003; Galantino et al., 2005; Klatt et al., 2009).”

“Specifically, clinical patients with hippocampal damage have been shown to evidence greatly reduced CAR dynamics (Buchanan et al., 2004) and positive associations between hippocampal volume and CAR amplitude have been demonstrated (Pruessner et al., 2007).”

“…states are associated with a propensity towards mental disorders such as depression and anxiety (Miller et al., 2009; Slavich and Irwin, 2014; Furtado and Katzman, 2015; Strawbridge et al., 2015) as well as an array of chronic medical illnesses (Aggarwal et al., 2006; Swardfager et al.,…”

“…the meditative components of this intensive retreat engaged neuroplastic brain mechanisms in a manner analogous to intensive learning regimes which have been shown to promote neuroplasticity partly through increase in BDNF signaling (Korol et al., 2013; Novkovic et al., 2015; Aarse et al., 2016).”

“Specifically, deep breathing, yoga and meditation practices have been found to increase vagal tone (Brown and Gerbarg, 2005; Khattab et al., 2007) which could be a potential mediating mechanism in the increased BDNF levels.”

“Given accumulating evidence that yoga and meditative practices modulate inflammatory and HPA activity (Jevning et al., 1978; Brown and Gerbarg, 2005; Kiecolt-Glaser et al., 2010; Bower and Irwin, 2015) and the possibility that yoga and meditative practices may positively impact BDNF levels as a…”

“…of BDNF—for example, BDNF upregulated IL-10 and transcription factor NF-κB in models of neuroinflammation investigating the neuroprotective effects of BDNF (Jiang et al., 2011) but also increased IL-4 and IFN-γ in in vitro studies of human peripheral blood mononuclear cells (Bayas et al., 2003).”

“A second recent study demonstrated a two-fold increase in BDNF when comparing pre- to post-values for a 12-week yoga and meditation lifestyle intervention involving approximately 90 min of practice daily (Tolahunase et al., 2017).”

“While some have reported an overall decrease in daily cortisol secretion followingmindfulness practice (Carlson et al., 2003, 2007;WitekJanusek et al., 2008), others have found no change (Robinson et al., 2003; Galantino et al., 2005; Klatt et al., 2009).”

“, 2004) and positive associations between hippocampal volume and CAR amplitude have been demonstrated (Pruessner et al., 2007).”

“…et al. (2003) and Witek-Janusek et al. (2008) both reported decreases in the anti-inflammatory IL-10 in breast and prostate cancer patients following MBSR, which might reflect a healthy improvement given baseline stress-induced immune dysregulation in this population (Witek-Janusek et al., 2007).”

“For example, acute exercise is known to increase the expression of both pro-inflammatory IL-1β and TNF-α as well as anti-inflammatory IL-6 and IL-10 (Northoff et al., 1994; Ostrowski et al., 1999).”

“BDNF has been relatively unexplored in work exploring the impact of meditative practices on biology to date, but one previous study showed that meditative yoga practice was related to increases in BDNF as well as heart rate variability (Pal et al., 2014).”

“Parasympathetic activation through the vagus nerve has been shown to increase BDNF levels as well as downstream activation of the BDNF receptor TrkB (Follesa et al., 2007; Furmaga et al., 2012).”

“…(ACTH) released from anterior pituitary gland, is a reliable marker of HPA activity and follows a robust circadian rhythm, which peaks 30 min after awakening (termed the ‘‘Cortisol Awakening Response’’—CAR) and gradually declines throughout the day (Akerstedt and Levi, 1978; Wüst et al., 2000).”

“In addition, Naveen et al. (2013) demonstrated that both yoga and antidepressant interventions led to increased levels of BDNF in patients with a history of depression.”

“These results are consistent with others who have reported increases in the CAR after mindfulness-based practices (Matousek et al., 2011).”

“Extensive previous work has demonstrated increased circulating BDNF levels due to both acute and chronic aerobic exercise regimes (Brunelli et al., 2012; Dinoff et al., 2016).”

“Similarly, Yeh et al. (2009) reported an increase in the pro-inflammatory cytokine IL-12 in diabetes patients after Tai chi practice, which was interpreted as related to an improvement toward metabolic regulation.”

“…the meditative components of this intensive retreat engaged neuroplastic brain mechanisms in a manner analogous to intensive learning regimes which have been shown to promote neuroplasticity partly through increase in BDNF signaling (Korol et al., 2013; Novkovic et al., 2015; Aarse et al., 2016).”

“…in the inhibition in the synthesis of pro-inflammatory cytokines generally (Mosser and Zhang, 2008), including TNFα, IL-1β, IL-12 and IFNγ (Zheng et al., 1996; Aste-Amezaga et al., Frontiers in Human Neuroscience | www.frontiersin.org 8 June 2017 | Volume 11 | Article 315 1998; Varma et al., 2001).”

“…one previous RCT of a hatha yoga intervention in patients with schizophrenia found no changes in BDNF or psychometric measures of resilience levels (Ikai et al., 2014), possibly indicating that such interventions are not as efficacious for individuals with severe psychotic illness, or at least…”

“In addition, BDNF is involved in the complex regulation of many diverse aspects of physiology such as inflammation, immunity, mood regulation, stress response and metabolism (Papathanassoglou et al., 2015).”

“Comparing those individuals who developed PTSD vs. those that did not indicated no difference between groups in IL-6 levels but significantly higher IL-10 levels in the more resilient individuals exposed to trauma but not experiencing PTSD (Teche et al., 2017).”

“…of BDNF—for example, BDNF upregulated IL-10 and transcription factor NF-κB in models of neuroinflammation investigating the neuroprotective effects of BDNF (Jiang et al., 2011) but also increased IL-4 and IFN-γ in in vitro studies of human peripheral blood mononuclear cells (Bayas et al., 2003).”

“…the meditative components of this intensive retreat engaged neuroplastic brain mechanisms in a manner analogous to intensive learning regimes which have been shown to promote neuroplasticity partly through increase in BDNF signaling (Korol et al., 2013; Novkovic et al., 2015; Aarse et al., 2016).”

“…scored low on anxiety and depression symptomatology, and when compared to previous literature in healthy normal populations (Kleiner et al., 2013; Krishnan et al., 2014) our levels were decreased in amplitude across the various cytokines obtained, likely indicating that in this sample there was…”

“Increasing evidence points towards the possibility that sustained engagement with meditative practices has both salubrious psychological and neurophysiological benefits (Cahn and Polich, 2006; Dahl et al., 2015; Tang et al., 2015; Luders and Cherbuin, 2016) and positively enhances biological functioning through both h…”

“First of all, the levels of BDNF [147, 148] and serotonin [149, 150] in serum are increased in different types of exercise.”

“…and neurochemical factors that also contribute to resilience, such as neuropeptide-Y (e.g., Reichmann & Holzer, 2016), cortisol awakening response (e.g., Cahn et al., 2017; Meggs, Golby, Mallett, Gucciardi, & Polman, 2016), and DHEA (e.g., Walker, Pfingst, Carnevali, Sgoifo, & Nalivaiko, 2017).”

“The growth factor BDNF promotes neurogenesis in the brain, and it may enhance resilience in humans (Cahn et al., 2017).”

“In specific patient groups or obese individuals, other studies document reductions in circulating levels of C-reactive protein (CRP) and IL-6,(49,50,53) although these findings were not replicated by some investigators.(48) Some of the cytokine-related effects of seated meditation, breathing practices, and yoga asana…”