Thoughts become things.

This isn't just some hippie-dippy, crunchy-granola, new-age construct (and don't get me wrong, I live for all things hippie-dippy). This is scientifically validated fact, well established in the peer-reviewed literature.

Mindset is instrumental to healing, since our thoughts influence our tendency towards inflammation, our propensity to develop pathology, the density of our brain matter, and our attainment of allostasis—the adaptive activation of neural, neuroendocrine and neuroendocrine immune mechanisms to maintain stability in the face of stressful challenges (McEwen, 1998). A meta-analysis of over three hundred articles by Segerstrom and Miller (2004) elucidated that physiological reactions to acute stressors serve adaptive functions, whereas chronic stress perturbs the finely orchestrated balance in the immune system and down-regulates both cellular and humoral (antibody-mediated) immune measures (Segerstrom & Miller, 2004).

Specifically, perceived stress increases hyper-coagulability and adhesion molecule expression making blood more 'sticky', creating a pro-atherogenic, pro-inflammatory environment conducive to the development of cardiovascular disease, immune imbalance, and a depressive mental state. In contrast, these pathophysiological changes are reversed by increased perception of uplifts (Jain, Mills, von Kanel, Hong, & Dimsdale, 2007).

Furthermore, psychosocial stress can perpetuate inflammation by mobilizing immature macrophages from bone marrow to initiate an inflammatory process (Segerstrom & Miller, 2004). These white blood cells, which are termed monocytes in the blood and macrophages in tissue, promote expression of pro-inflammatory genes that enhance release of inflammatory cellular messengers, or cytokines, while also decreasing sensitivity to cortisol, the stress hormone which neutralizes inflammation (Segerstrom & Miller, 2004). Without cortisol to buffer inflammation, it can run unchecked and result in chronic, long-latency diseases such as mood disorders, autoimmune conditions, and cardiovascular disease.

Rosenkranz and colleagues (2016) summarize the effect of stress on disease, with, "Psychological stress is a major contributor to symptom exacerbation across many chronic inflammatory conditions and can acutely provoke increases in inflammation in healthy individuals," a phenomenon which is relevant within the landscape of mood disorders, and more specifically depression (p. 117).

As discussed in A Mind of Your Own, depression is a disorder of inflammation, not neurotransmitter deficiency. This is evidenced by the fact that increases in the pro-inflammatory acute phase reactant, C-reactive protein (CRP), as well as elevations in inflammatory cytokines such interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), predict risk for depression (Hoyo-Becerra, Schlaak, & Hermann, 2014). This is also revealed by the fact that interferon-α therapy for hepatitis C triggers abnormalities in brain metabolism, immune responses, and hypothalamic-pituitary-adrenal axis activity, as well as perturbations in neurogenesis, neurotrophic signaling, and synaptic plasticity in a manner resembling that of depressive states (Hoyo-Becerra, Schlaak, & Hermann, 2014). Many of these pathogenic changes that result from interferon-α are correlated with the increases in IL-6 and TNF-α that it generates (Hoyo-Becerra, Schlaak, & Hermann, 2014).

Because stress precipitates an inflammatory molecular cascade, stress management strategies should be employed as part of a comprehensive, root-cause resolution, lifestyle medicine approach to depression. Mindfulness practices such as meditation, which may be the ultimate method of stress reduction, have proven benefits for mood improvement, relief from chronic pain, and coping with chronic stress (Field, 2011).

Specifically, mindfulness practices can mitigate stress-induced pathophysiological changes by enhancing gray matter concentration within the hippocampus, the posterior cingulate cortex, the temporo-parietal junction, and the cerebellum—brain regions involved in executive functions such as "learning and memory processes, emotion regulation, self-referential processing, and perspective taking" (Holzel et al., 2011).

Another study demonstrated that decreased stress and inflammatory responses, as evidenced by a decreased capsaicin-induced flare response and a decreased level of salivary cortisol, was observed in experienced meditators compared to age and sex-matched controls (Rosenkranz et al., 2016). The experienced meditators also exhibited smaller neurogenic inflammatory responses, a process which is not only inherent to the pathology of depression, but also underlies other chronic inflammatory diseases such as atopic and autoimmune disorders (Rosenkranz et al., 2016). Thus, this research illustrates that meditation can buffer the effects of stress reactivity and mitigate the neuro-inflammation that underscores depression, thus imparting therapeutic benefit in both mood disorders and other chronic inflammatory conditions.

What's more, protective psychological factors associated with wellbeing and resilience were reported by experienced meditators (Rosenkranz et al., 2016). Similarly, another review found that, "meditation may enhance cognitive and psychological health via neuroplastic effects on brain structures and circuits that influence attention, memory, and emotional regulation" (Acevedo, Pospos, & Lavretsky, 2016, p. 333). They continue to note that, "Although these findings do not support stress buffering and relief models of meditation and yoga, it is likely that enhancement of these functions may indirectly alleviate stress. For example, by exerting greater self-control, individuals may better regulate their thoughts and emotions, thus possibly resulting in adaptive responses to stress" (Acevedo, Pospos, & Lavretsky, 2016, p.333)

In addition, a meta-analysis by Tang, Holzel, and Posner (2015) found that mindfulness meditation consistently affected morphology in six brain regions, including the anterior and posterior cingulate, which function in attention, the amygdala, which regulates emotionality, the insula, which is active in sensory awareness, the prefrontal cortex, responsible for cognition, reasoning, decision-making, and executive control, and the striatum, which takes part in learning and motivation. Based on these structural changes, the authors conclude that meditation benefits are conferred by alterations in the neural circuitry that regulate self- awareness, emotional processing, and present-moment awareness (Tang, Holzel, & Posner, 2015).

On a related note, the dorsolateral prefrontal cortex (DLPFC), a brain region which functions in assessment of rewards, self-control, and sense of agency, has been shown to be dysregulated in mood disorders (Koenigs & Grafam, 2009). Meditations that incorporate active postures, hand movements, and chanting have been observed to uniquely activate the DLPFC and consequently improve mood, depression, anxiety, fatigue, and stress (Innes, Selfe, Brown, Rose, & Thompson-Heisterman, 2012; Lavretsky et al., 2012).

This phenomenon is illuminated by a study of brief daily yogic meditation in dementia caregivers with mild depressive symptoms, where "The meditation group showed significantly lower levels of depressive symptoms and greater improvement in mental health and cognitive functioning compared with the relaxation group" (Lavretsky et al., 2013, p. 57). Another study of a two month Kirtan Kriya meditation program for patients with memory loss was associated with positive changes in neuropsychological parameters and improvements in mood, anxiety, and cerebral blood flow (CBF) (Moss et al., 2012).

So, what other mindfulness practices can you apply? How can you engage in holistic approaches which foster a positive mindset, and enable you to replace maladaptive coping mechanisms with healing thoughts that serve your recovery?

To manage mindset and mitigate stress, mindfulness-based stress reduction (MBSR) or other meditative techniques can be employed, as can affirmations, cognitive reframing, visualizations, heart rate variability training tools such as Heart Math, emotional freedom technique (EFT), music therapy, yoga, tai chi, qigong, and biofeedback.

If these therapies seem a little too "out there" for you, consider this: guided imagery and music (GIM) practices have been demonstrated to improve physical distress, perceived stress, mood disturbances, well-being, and cortisol concentrations in individuals on long-term sick leave, and result in faster job return (Beck, Hansen, & Gold, 2015). Moreover, visualization techniques also alleviate subjective pain and depression in fibromyalgia and significantly reduce sedentary behavior while promoting engagement with physical activity in obese individuals (Onieva-Zafra, Garcia, & Del Valle, 2015; Weigensberg et al., 2014).

Similarly, a twelve-week randomized controlled trial showed that yoga significantly decreased depression and perceived stress in women suffering from elevated depressive symptoms (Chu et al., 2017). The twice a week, sixty-minute yoga sessions, which were comprised of breathing exercises, yoga poses, and supine meditation, also increased parasympathetic tone, as highlighted by increases in heart rate variability (HRV) (Chu et al., 2017). The up-regulation in parasympathetic nervous system (PNS) activity is key, as this "rest and digest" or "feed and breed" branch of the autonomic nervous system is required for proper immune function, digestion, and regenerative processes essential to healing. In particular, the anti-inflammatory effects of the PNS are mediated by descending cholinergic anti-inflammatory activity through the vagal nerve (Ulloa, 2005; Wang et al., 2003).

The anti-inflammatory effect of yoga and other mindfulness practices are operationalized via stimulation of the vagal nerve, the primary parasympathetic nerve, via a nicotinic anti-inflammatory pathway dependent on the α7 nicotinic acetylcholine receptor (α7nAChR). Mechanistically, inflammatory cytokine-generating immune cells such as macrophages, lymphocytes, and microglia express nicotinic acetylcholine receptors (AChRs), which when activated by vagal nerve activity, relay an intracellular signal to suppress nuclear translocation of the transcription factor NFkB, and therefore inhibit synthesis of cytokines including IL-1, IL-6, IL-8, TNF-alpha as a result (Wang et al., 2004). In essence, "Vagus nerve-derived cholinergic signals provide tonic or continuous modulation of cytokine synthesis, functioning as a governor on an engine that limits the magnitude of the immune response" (Tracey et al., 2017, p. 291).

This is evidenced in the peer-reviewed literature, where yoga has also been demonstrated to lower basal levels of TNF-α and IL-6, molecular messengers implicated in depression, thus protecting "against inflammatory diseases by favorably altering pro-inflammatory cytokine levels" (Vijayaraghava, Doreswarmy, Narasipur, Kunnavil, & Srinivasamurthy, 2015). Moreover, in a review of twenty-six randomized controlled trials on therapies including tai chi, qigong, yoga, and meditation, authors found that mindfulness strategies significantly decreased expression of inflammation-related genes and reduced signaling though NF-κB, a transcription factor that promotes the expression of inflammatory genes (Bower & Irwin, 2016). In other words, mindfulness practices promote parasympathetic vagal tone, which modulates the immune response to inhibit the pathogenic inflammatory cascade behind everything from cardiovascular disease, to autoimmunity, to mood disorders.

In particular, there is immense therapeutic potential in yoga for mood disorders, as elucidated by a meta-analysis by Fox and colleagues of twenty-one studies, which demonstrated that yoga produced significant structural differences in eight brain regions, such as the frontopolar cortex, sensory cortex and insula, anterior and mid-cingulate, and orbitofrontal cortex, areas that play a role in attention, awareness, and emotional regulation (Fox et al., 2014). In fact, "Many of these regions are also affected in cognitive and mood disorders" (Acevvedo, Pospos, & Lavretsky, 2016, p. 330).

Another study, which examined the effect of six weeks of yoga and meditation on the levels of perceived stress and wellbeing in medical students prior to test-taking, showed that significant improvements in feelings of peace, focus, endurance, happiness, positivity, personal satisfaction, self-confidence, patience, and fatigue were observed (Prasad, Varrey, & Sisti, 2016). This is important, because across a spectrum of medical conditions, positive beliefs and expectancy regarding illness prognosis confers increased well-being, quality of life, and improved outcomes (Hurt et al., 2014).

This is consistent with findings that, "Mind - body interventions are relayed via the downregulation of stress, mainly through the hypothalamic - pituitary - adrenal (HPA) axis, known for its role in stress control, and the SNS [sympathetic nervous system]" (Acevedo, Pospos, & Lavretsky, 2016). This phenomena is witnessed in populations with depression, where studies have highlighted that yoga is correlated with reductions in plasma cortisol (Acevedo, Pospos, & Lavretsky, 2016). Another study showed that even a two month trial of Vinyasa yoga, where a flowing sequence of poses is performed, led to decreased depression (Uebelacker et al., 2010). Field (2011) attributes the correlation between yoga and decreased depression both to decreases in cortisol levels and to increases in brain alpha waves that accompany yoga sessions, the latter of which signify induction of the aforementioned relaxation response (Kamei et al., 2009).

Mind-body therapies influence inflammatory biology via neuroendocrine mechanisms, or in layman's terms, through their effects on both the neurological and hormonal systems. As previously mentioned, downstream stress-response pathways, such as the autonomic nervous system (ANS), which modulates the balance between the sympathetic, fight-or-flight arm and the parasympathetic, rest-and-digest arm, as well as the hypothalamic-pituitary-adrenal (HPA) axis, which controls stress hormone production, are regulated by neural regions that are impacted by mind-body interventions (Bower & Irwin, 2016).

In turn, the ANS and HPA axis affect synthesis of pro-inflammatory cytokines through the effects of their molecular messengers on glucocorticoid, cholinergic, and adrenergic receptors located on immune cells. In this way, the science behind mind-body therapies exemplifies how chronic illnesses are well-explained within the landscape of the emerging field of psychoneuroimmunology, and how mindfulness can produce changes in multiple interconnected body systems.

For those who are spiritually inclined, religious practices such as prayer or mantras can serve the same purpose as meditation. Spirituality has been revealed to be cardioprotective, as it is correlated with significantly lower levels of systolic and diastolic ambulatory blood pressure, high sensitivity C-reactive protein (an inflammatory biomarker), fasting glucose, and triglycerides (Holt-Lunstad, Steffen, Sandberg, & Jensen, 2011). There is also evidentiary support that another Eastern tradition, tai chi, both improves the oxidative stress response and enhances DNA repair mechanisms (Huang, Eungpinichpong, Silsirvanit, Nakmareong, & Wu, 2014).

In essence, each of these stress-management therapies are unique in their ability to induce a relaxation response, which down-regulates pro-inflammatory molecular cascades and up- regulates transcription of genes associated with mitochondrial energy production, energy metabolism, insulin secretion, and telomerase secretion (conferring anti-aging benefits) (Bhasin et al., 2013).

Thoughts matter. You have a choice.

You can see yourself as a victim, a hapless bystander to extraneous circumstances beyond your sphere of influence - or develop a stronger internal "locus of control," a paradigm from social psychology that predicts positive mental health outcomes. One way to reclaim agency in your health care management is to engage with these therapeutic mindfulness techniques, as they are associated with an increased sense of autonomy.

Lastly, start viewing yourself as the arbiter of your own fate, and the captain of your own destiny. Externality of locus of control, or attribution of one's circumstances to external forces such as chance, fate, or luck of the draw, is associated with higher rates of depression (Zawai & Hamaideh, 2009). In contrast, people with an internal locus of control, or the orientation that outcomes in their lives are contingent upon their own actions and efforts, tend to be more resilient in the face of adversity. There also exists an inverse relationship between internality of locus of control and depression, such that people with an internal locus of control tend to be less depressed (Zawai & Hamaideh, 2009).

Of course, mindfulness practices cannot occur in a vacuum. Reversing mood disorders such as anxiety and depression requires a multi-pronged approach, which incorporates a whole foods, nutrient-dense, anti-inflammatory diet, targeted supplementation, restorative sleep, customized exercise regimens, and social support.

So commit to one of these mind-body practices. Starting out is akin to your first time riding a bicycle - scary and awkward, a bit wobbly and off-center.

You're afraid of letting go, trusting your body, and surrendering wholeheartedly to the experience. But after some trial runs, you can take off the training wheels and eventually the practice becomes second nature - a place of solace, serenity, and freedom.


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About the author

Ali Le Vere holds dual Bachelor of Science degrees in Human Biology and Psychology, minors in Health Promotion and in Bioethics, Humanities, and Society, and is a Master of Science in Human Nutrition and Functional Medicine candidate. Having contended with chronic illness, her mission is to educate the public about the transformative potential of whole foods nutrition and to disseminate information on evidence-based, empirically rooted holistic healing modalities. Read more at Science-based natural remedies for autoimmune disease, dysautonomia, Lyme disease, and other chronic, inflammatory illnesses.