Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to psychosocial stress

“…increased levels of plasma IL-6 (and/or its downstream product c-reactive protein) predict the development of a number of disease states, including vascular disease, diabetes and dementia (Ridker, 2000; Pradhan et al., 2001; Kiecolt-Glaser et al., 2003; Perry et al., 2007; Steptoe et al., 2007).”

“…data demonstrate that naturalistic life stress increases IL-6 and that elevated plasma levels of IL-6 are a risk factor for the development and/or progression of a number of disease states (Ridker, 2000; Pradhan et al., 2001; Kiecolt-Glaser et al., 2003; Perry et al., 2007; Steptoe et al., 2007).”

“…increased levels of plasma IL-6 (and/or its downstream product c-reactive protein) predict the development of a number of disease states, including vascular disease, diabetes and dementia (Ridker, 2000; Pradhan et al., 2001; Kiecolt-Glaser et al., 2003; Perry et al., 2007; Steptoe et al., 2007).”

“Major depression has also been repeatedly associated with increased plasma concentrations of IL-6 (Raison et al., 2006).”

“reported that training in mindfulness meditation enhanced antibody production following influenza vaccination (Davidson et al., 2003), and Carlson et al.”

“However, responses to laboratory stressors have been cross-sectionally associated with behavioral states such as depression (Heim et al., 2000; Pace et al., 2006), which might affect ability to engage in meditation practice.”

“Although little is known regarding the effect of compassion meditation (or other compassion training techniques) on stress-related behavioral and neurobiological responses (Carson et al., 2005; Gilbert and Procter, 2006; Lutz et al., 2008a), interest in compassion meditation within the research community has heightene…”

“For example, self-compassion (but not self esteem) was associated with less anxiety in response to a mock job interview and less distress after receiving neutral feedback in response to a videotaped speech performance (Leary et al., 2007; Neff et al., 2007).”

“…in turn, has been associated with a variety of desirable endpoints, including reductions in perceived stress, burnout, depression, and anxiety as well as increases in life satisfaction (Neff et al., 2005; Shapiro et al., 2005; Gilbert et al., 2006; Neff et al., 2007; Shapiro et al., 2007).”

“Increasing evidence suggests that meditation practices may impact physiological pathways, including the immune and neuroendocrine systems, which are modulated by stress and are relevant to disease development and progression (Taylor, 1995; Carlson et al., 2003, 2007; Davidson et al., 2003; Hidderley and Holt, 2004; Os…”

“…the TSST. Interestingly in this regard, an association between practice time and physiological, behavioral or neural outcomes has been observed in the three prior published studies that have examined compassion-based meditation practices (Lutz et al., 2004; Carson et al., 2005; Lutz et al., 2008b).”

“Self-compassion, in turn, has been associated with a variety of desirable endpoints, including reductions in perceived stress, burnout, depression, and anxiety as well as increases in life satisfaction (Neff et al., 2005; Shapiro et al., 2005; Gilbert and Procter, 2006; Neff et al., 2007; Shapiro et al., 2007).”

“Innate immune inflammatory signaling pathways are increasingly implicated in the pathogenesis of vascular disease (Willerson and Ridker, 2004), cancer (Aggarwal et al., 2006; Hiratsuka et al., 2006), diabetes (Pradhan et al.”

“Innate immune inflammatory signaling pathways are increasingly implicated in the pathogenesis of vascular disease (Willerson and Ridker, 2004), cancer (Aggarwal et al.”

“…increased levels of plasma IL-6 (and/or its downstream product c-reactive protein) predict the development of a number of disease states, including vascular disease, diabetes and dementia (Ridker, 2000; Pradhan et al., 2001; Kiecolt-Glaser et al., 2003; Perry et al., 2007; Steptoe et al., 2007).”

“…that these pathways may be a mechanism by which stress and depression are transduced into medical illness (Lutgendorf et al., 1999; Goebel et al., 2000; Bierhaus et al., 2003; Kiecolt-Glaser et al., 2003; Kiecolt-Glaser et al., 2005; McDade et al., 2006; Pace et al., 2006; Danese et al., 2007).”

“…in turn, has been associated with a variety of desirable endpoints, including reductions in perceived stress, burnout, depression, and anxiety as well as increases in life satisfaction (Neff et al., 2005; Shapiro et al., 2005; Gilbert et al., 2006; Neff et al., 2007; Shapiro et al., 2007).”

“…data demonstrate that naturalistic life stress increases IL-6 and that elevated plasma levels of IL-6 are a risk factor for the development and/or progression of a number of disease states (Ridker, 2000; Pradhan et al., 2001; Kiecolt-Glaser et al., 2003; Perry et al., 2007; Steptoe et al., 2007).”

“Third, metta practices have been shown to increase self-compassion (Shapiro et al., 2005; Shapiro et al., 2007).”

“Innate immune inflammatory signaling pathways are increasingly implicated in the pathogenesis of vascular disease (Willerson and Ridker, 2004), cancer (Aggarwal et al., 2006; Hiratsuka et al., 2006), diabetes (Pradhan et al.”

“…that have examined the relative engagement of research subjects in compassion meditation techniques (Carson et al., 2005; Lutz et al., 2008a; Lutz et al., 2008b), we also sought to assess the extent of participation in the compassion meditation program (as reflected by class attendance and…”

“Interestingly, both stress (acute and chronic) and major depression are also associated with increased activity in innate immune inflammatory pathways, suggesting that these pathways may be a mechanism by which stress and depression are transduced into medical illness (Lutgendorf et al., 1999; Goebel et al., 2000; Bie…”

“Increasing evidence suggests that meditation practices may impact physiological pathways, including the immune and neuroendocrine systems, which are modulated by stress and are relevant to disease development and progression (Taylor, 1995; Carlson et al., 2003; Davidson et al., 2003; Hidderley et al., 2004; Carlson et…”

“…that these pathways may be a mechanism by which stress and depression are transduced into medical illness (Lutgendorf et al., 1999; Goebel et al., 2000; Bierhaus et al., 2003; Kiecolt-Glaser et al., 2003; Kiecolt-Glaser et al., 2005; McDade et al., 2006; Pace et al., 2006; Danese et al., 2007).”

“…pathways, including the immune and neuroendocrine systems, which are modulated by stress and are relevant to disease development and progression (Taylor, 1995; Carlson et al., 2003; Davidson et al., 2003; Hidderley et al., 2004; Carlson et al., 2007; Ospina et al., 2007; Tang et al., 2007).”

“…the induction of innate immune inflammatory pathways in response to psychosocial stress may also represent a mechanism linking stress to depression, given that humans chronically exposed to innate immune cytokines for therapeutic purposes develop high rates of depression (Raison et al., 2005).”

“…to an influenza vaccine in healthy subjects (Davidson et al., 2003) or with a variety of immune, neuroendocrine or behavioral parameters in patients with cancer (Carlson et al., 2003; Carlson et al., 2004) or with depressive symptoms in patients with rheumatoid arthritis (Sephton et al., 2007).”

“…and outcome failed to show an effect of group assignment (i.e. the group randomized to meditation did not separate from that control condition) (Shapiro et al., 2003; Pradhan et al., 2007), whereas several recent studies reporting a significant effect of group assignment found no relationship…”

“Because cortisol and IL-6 demonstrate circadian variability (Posener et al., 1996; Vgontzas et al., 2005), we also included time of stressor initiation as a covariate in all analyses of these variables.”

“…that these pathways may be a mechanism by which stress and depression are transduced into medical illness (Lutgendorf et al., 1999; Goebel et al., 2000; Bierhaus et al., 2003; Kiecolt-Glaser et al., 2003; Kiecolt-Glaser et al., 2005; McDade et al., 2006; Pace et al., 2006; Danese et al., 2007).”

“Most of our participants practiced less than the recommendation of one session per day, and less than has been reported in some (Carlson et al., 2003; Carmody and Baer, 2007; Pradhan et al., 2007), but not all (Davidson et al.”

“…regarding the effect of compassion meditation (or other compassion training techniques) on stress-related behavioral and neurobiological responses (Carson et al., 2005; Gilbert et al., 2006; Lutz et al., 2008a), interest in compassion meditation within the research community has heightened…”

“The current study adds to a conflicting literature on whether meditation affects peripheral cortisol levels, and if so,whether it increases or decreases cortisol release (MacLean et al., 1997; Robinson et al., 2003; Carlson et al., 2004; Robert McComb et al., 2004;Walton et al., 2004; Ospina et al., 2007).”

“Interestingly, both stress (acute and chronic) and major depression are also associated with increased activity in innate immune inflammatory pathways, suggesting that these pathways may be a mechanism by which stress and depression are transduced into medical illness (Lutgendorf et al., 1999; Goebel et al., 2000; Bie…”

“Moreover, recent data indicate that cortisol responses to stress maymodulate IL-6 responses and thusmay contribute to long-term effects of stress on disease development via modulatory effects on the innate immune response (Bower et al., 2007).”

“The current study adds to a conflicting literature on whether meditation affects peripheral cortisol levels, and if so,whether it increases or decreases cortisol release (MacLean et al., 1997; Robinson et al., 2003; Carlson et al., 2004; Robert McComb et al., 2004;Walton et al., 2004; Ospina et al., 2007).”

“…pathways, including the immune and neuroendocrine systems, which are modulated by stress and are relevant to disease development and progression (Taylor, 1995; Carlson et al., 2003; Davidson et al., 2003; Hidderley et al., 2004; Carlson et al., 2007; Ospina et al., 2007; Tang et al., 2007).”

“Increasing evidence suggests that meditation practices may impact physiological pathways, including the immune and neuroendocrine systems, which are modulated by stress and are relevant to disease development and progression (Taylor, 1995; Carlson et al., 2003, 2007; Davidson et al., 2003; Hidderley and Holt, 2004; Os…”

“Because cortisol and IL-6 demonstrate circadian variability (Posener et al., 1996; Vgontzas et al., 2005), we also included time of stressor initiation as a covariate in all analyses of these variables.”

“The current study adds to a conflicting literature on whether meditation affects peripheral cortisol levels, and if so,whether it increases or decreases cortisol release (MacLean et al., 1997; Robinson et al., 2003; Carlson et al., 2004; Robert McComb et al., 2004;Walton et al., 2004; Ospina et al., 2007).”

“Although there were no between-group effects, within the meditation group greater meditation practice was associated with fewer social stressinduced increases in IL-6 and emotional distress (Pace et al., 2009).”

“Pace et al. (2008) found that compassion-focused meditations reduced stress-linked immune and behavioural responses.”

“Therefore, the active control condition is hardly better than a treatment-as-usual comparison.”

“…on the cultivation of compassion (Kirby, 2016): Compas-sion Focused Therapy (CFT; Gilbert, 2014), Mind-ful Self-Compassion (MSC; Neff & Germer, 2013 Pace et al., 2009), Cultivating Emotional Balance (CEB; Kemeny et al., 2012), and Loving-Kindness (LKM) and Compassion Meditations (CM; e.g.,…”

“F or p er so na l u se o nl y. meditation (Pace et al. 2009), and Compassionate Mind Therapy (Gilbert 2009).”

“…interventions that have been used for the treatment of fear- and anxiety-based disorder, such as community-based educational intervention, exercise, yoga, and mediation, have also been associated with decreases in inflammation (Bower and Irwin, 2016; Pace et al, 2009; Villablanca et al, 2015).”

“…these results, in a randomized active control (health education) longitudinal study of compassion-based meditation, Pace et al. (Pace et al., 2010; Pace et al., 2009) found decreased IL-6 and cortisol activations after the TSST in the meditation training group, but only for those who practiced…”

“Compassion meditation decreases inflammatory (IL-6) responses to a psychosocial laboratory stressor (157).”

“2008) and health (Pace et al. 2009), the current data show that responding to potentially distressing situations with compassion benefits the person who experiences it through strengthening positive affect.”

“…3/21/12; Revision accepted 11/1/12 that compassion training can improve personal wellbeing, including stress-related immune responses (Pace et al., 2009), positive affect (Fredrickson, Cohn, Coffey, Pek, & Finkel, 2008; Hutcherson, Seppala, & Gross, 2008), and psychological and…”

“From a biological perspective, the practice of CM has been shown to reduce stress-linked immune responses (Pace et al. 2009).”

“For example, Pace et al. (2009) found a post-hoc association between compassion meditation practice time and decreased levels of interleukin-6, a pro-inflammatory cytokine, although there was no difference between the meditation group and the control group overall.”

“There were no significant changes in the strength of association for any of the baseline correlations from pre-to post-CCT (all ps [ .11) and from pre-to-post WL (all ps [ .16) (Table 3).”

“, 2003) or meditation that also reduces IL-6 responses (Pace et al., 2009).”

“Self-benefiting effects of compassion training such as increases in positive mood, life satisfaction, decreased depressive symptoms [21], and less reactivity to psychosocial stress [23] have been reported before.”

“Behavioral interventions that reduce stress, such as exercise, yoga or meditation, can affect the HPA and SNS axes as well as the immune system [255], and may also serve as potential treatments for PTSD and related comorbidities.”

“…responses to real-world, strongly evocative social contexts, such as those included in the TSST, can be moderated by such interventions (see Pace et al., 2009, for a study that did not yield main effects on biological outcomes in response to this stressor paradigm of a less intensive…”

“production, there is mixed evidence that MBTs influence cortisol reactivity to acute stress; for example, a study of compassion meditation found no effect on cortisol reactivity to the Trier Social Stress Task (TSST), a standardized psychosocial stressor (Pace et al., 2009), whereas a study of brief mindfulness traini…”

“(Pace et al., 2009a; Lipizzi, 2011) 89 Medically healthy undergraduate students 18.5 (SD !”

“…lifetime practice hours and outcome variables such as interospective abilities (Fox et al., 2012), and brain structure (Lazar et al., 2005), and some longitudinal training studies also demonstrate dose-dependent effects (e.g., Carmody and Baer, 2008; Pace et al., 2009; Rosenzweig et al., 2010).”

“These findings are similar to previous studies of meditation for general health outcomes (Marchand 2014; Pace et al. 2009) and non-RCTs of meditation for prosocial outcomes (Klimecki et al. 2012, 2014; Leiberg et al. 2011) and further support a neural and physiological basis for meditation’s…”

“2 A recent study by Raison and colleagues (Pace et al., 2008) also uses an active”

“…Mindful Self-Compassion (Neff & Germer, 2013), the Compassion Cultivation Training (Jazaieri et al., 2013), Cognitively Based Compassion Training (Pace et al., 2009), Cultivating Emotional Balance (Kemeny et al., 2012), and Compassion and Loving-Kindness Meditations (e.g., Hoffmann, Grossman, &…”

“Initial studies of CBCT have demonstrated improved immune response to psychosocial stressors in healthy adults (Pace et al. 2009).”

“Finally, a third RCT found that adults who reported home practice times above the median during a 6-week compassion meditation training program exhibited significantly lower stress-induced levels of negative emotion and inflammation (interleukin-6) post-intervention compared to individuals below the home practice medi…”

“…and social-evaluative threat have been reliably shown to evoke increases in measures of physiological stress and peripheral inflammation (Dickerson and Kemeny, 2004; Dickerson et al., 2009; Gruenewald et al., 2004; Kirschbaum et al., 1993; Pace et al., 2009; Rohleder et al., 2006).”

“By focusing on training in self-compassion rather than the range of self-and other-compassion, concentration, and mindfulness practices taught in the Pace et al. (2009) study, our study more clearly links the self-compassion dimension of compassion training to adaptive social threat responding.”

“IL-6 Chen 2006 (QG) [69], Creswell 2012 (Med) [37], Irwin 2012; Irwin 2007 (TC) [60,61], Janelsins 2011[63], Sprod 2012 (TC) [65], Malarkey 2013 (Med) [51], McCain 2008 (TC) [64], Oken 2010 (Med) [43], Pace 2009 (Med) [44], Pullen 2008 (Yoga) [54], Pullen 2010 (Yoga) [55], Zautra 2008 (Med) [49] 6 to16 594 2 High; 2 M…”

“In addition to strategies directly targeting the immune system, psychosocial interventions might be used to reduce inflammation in traumatized children (Pace et al. 2009) and to decrease psychosocial adversity more generally (Miller et al.”

“…Leen-Feldner, sed Cognitive Therapy Improves Emotional Reactivity to Social (2011), 10.1016/j.beth.2011.08.006 2007; Ortner, Kilner, & Zelazo, 2007; Pace et al., 2009; Proulx, 2008; Raes et al., 2009; Tang et al., 2007; Taylor et al., 2011; Vujanovic, Zvolensky, Bernstein, Feldner, & McLeish,…”

“The first eligible RCT assessed the effects of Cognitivebased Compassion Training (CBCT) on stress reactivity in 89 healthy adults (aged 17–19 years; mean age=18.5 years, SD= 0.62 years) (Pace et al. 2009).”

“…indicate that dementia caregivers who practice meditation show improvement in mental health indices such as depression and anxiety (Waelde et al., 2004; Van Puymbroeck et al., 2007; Pace et al., 2009), which are indices associated with inflammatory markers such as IL-6 (Irwin and Olmstead, 2011).”

“In addition, OT administration impacts responses to psychosocial stress (TSST) in ways similar to changes observed with CBCT (Pace et al., 2009).”

“Of notable interest is an intervention known as cognitively based compassion therapy (CBCT; Pace et al., 2009).”

“For example, investigators found that the more people practiced compassion meditation over a 6-week period the less was their stress-induced IL-6 responsivity (involved in the immune response) as well as self-reported stress reactivity (Pace et al., 2009).”

“Traditional accounts of the compassion practice suggest that, even if strong personal distress can occur during compassion meditation, this distress is alleviated by two factors: 1) cultivating an equanimity stance toward suffering, in particular one's own suffering, such that one is able to bring suffering to mind wi…”

“, 6 weeks).(36) Another study showed that exercise such as running causes erratic but significant increase in both b-endorphin and corticotropin-releasing hormone, while meditation increases only the latter.”

“Meditation that focuses on increasing compassion for others has also been shown to reduce stress-inducted inflammation (Pace et al., 2009).”

“Median split approach has been used in similar studies to examine difference between groups high and low in a specific variable (Campbell et al. 2012; Pace et al. 2009, 2010).”

“Neuroscientists have found that individuals who are able to visualize compassionate images can derive considerable physiological and psychological benefits (Lutz, Brefczynski-Lewis, Johnstone, & Davidson, 2008; Pace et al., 2009).”

“…been found to modulate inflammatory signaling in the innate immune system including aerobic exercise (Nicklas et al., 2008), compassion meditation (Pace et al., 2009) and Tai Chi (Irwin and Olmstead, 2011; Lavretsky et al., 2011) in association in improvements in sleep disturbance, for example.”

“While the mindfulness components incorporated into CBCT may provide an immediate and effective stress management and coping technique, the physiological benefits associated with practices specific to CBCT may confer additional health-relevant benefits (Pace et al. 2009; Pace et al. 2010).”

“Similarly, evidence suggests that clients who practice meditation regularly in studies of compassion-based meditation training exhibit better outcomes than clients who do not (Pace et al., 2009).”

“The practice of Yoga and physical exercise are different entities, the former results in energy conservation with economy of energy expenditure for mental and physical benefits, and the later results in energy expendituremore for physical exertions andmetabolic needs, as is evident from a study which showed exercise c…”

“Mindfulness decreases infl ammatory responses to a psychosocial laboratory stressor (Pace et al. 2009).”

“For example, in an RCT of a six-week long compassion meditation program (based on the Tibetan Buddhist ‘Mind Training’ technique), Pace et al (2009) demonstrated that meditators (healthy adults) experienced significant reductions in adverse psychosomatic responses to psychosocial stress.”

“Practice time effects may also extend to physiological responses, including inflammatory response to laboratory stress (66).”

“Pace et al. (2009) recruited 61 college students into a study comparing compassion meditation and health education discussion.”

“The mean inter- and intra-assay coefficients of variation for control samples in this assay are reliably 10% or less [116].”

“For instance, a compassion meditation intervention reduced emotional distress and IL-6 for people who practiced more frequently than less frequently.[131] In addition, the regular practice of yoga was related to lower baseline and stress-induced inflammation.”

“…increased empathy for oneself and others would be expected to enhance prosocial behavior in ways likely to reduce psychosocial stress, our group initially developed CBCT as a behavioral intervention to reduce deleterious behavioral and physiological stress responses (Pace et al., 2009, 2010).”

“Mediterranean) [93, 94], as well as meditation and yoga [95, 96], have been shown to reduce peripheral inflammatory markers.”

“2008), and previous studies showing higher induced (Pace et al. 2009) and trait self-compassion (Breines et al.”

“While research on mindfulness dominates the field, increasing numbers of studies investigate compassion (e.g., Pace et al., 2009; Desbordes et al., 2012), visualizationbased meditation practices (e.g., Kozhevnikov et al., 2009), equanimity (e.g., Desbordes et al., 2014), etc.; and there are also…”

“Pace et al. (2009), however, examined the effects of compassion meditation drawn from the practice of Lojong, but only in the context of altered stress responses and not related empathy or altruism.”