The biological implications of meditation practices in the treatment of depression

Major depressive disorder (MDD) is a common mood disorder and a great cause of disability worldwide. Biological factors implicated in MDD range from neural imbalances to signaling dysregulations (which are partly grounded in genetic predispositions).

As shown in Figure 1, the socio-cognitive and biological deficiencies involved in MDD appear to influence each other in a circular, perpetuating manner. These deficiencies can be categorized into six non-exhaustive broad factors, i.e., mood, executive functioning, social skills, neuroplasticity, neural core networks, and neuroendocrine and neuroimmunological factors. The modulation of one factor is expected to exert an effect over the other factors, and subsequently to affect the overall depressive symptomology. Importantly, although these factors seem to play a causal role in the symptoms of MDD to various degrees, the precise causes of depression have not yet been entirely determined. There are, for instance, other psychological (e.g. cognitive biases) and biological factors (e.g. serotonin transporter genotype) that are known to be involved in depression, however these will not be covered in this article.

FIGURE 1 | A model of psychological and biological deficiencies associated with major depressive disorder; rounded square-shaped box, deficient factor(s); oval- shaped box, mediating factor(s); white box, psychological factor; gray box, biological factor; arrow, unidirectional influence; BDNF, brain-derived neurotrophic factor. Taken from Heuschkel and Kuypers (2020)

Particularly impaired in individuals with MDD is neuroplasticity, a crucial neural mechanism that entails structural and functional brain adaptations in response to altered environmental circumstances. This impairment is generally indicated by abnormally low levels of the brain-derived neurotrophic factor (BDNF), which is related to hippocampal and prefrontal atrophy in MDD. Moreover, impairments in stress regulation and immune system functioning have also been associated with the development of MDD symptoms. The following paragraphs describe in more detail the roles of BDNF, as well as those of cortisol, as a marker of stress, and of inflammatory cytokines in mental health, with a focus on depression.

BDNF is an important neurotrophin which promotes neuronal development, survival and plasticity in the central and peripheral nervous systems. It is most active in brain areas that play a role in learning, memory and higher cognition, such as the hippocampus and cortex. BDNF is also pivotal in the regulation of several physiological aspects, including stress response, mood, inflammation and metabolism. Decreases in BDNF levels have been linked to psychiatric and neurological disorders, such as depression, anxiety and Alzheimer’s disease.

Cortisol is a glucocorticoid secreted by the adrenal glands and, as part of the hypothalamic-adrenal-pituitary (HPA) axis, is a reliable marker for stress response. Cortisol is also part of the feedback mechanism in the immune system, where its role is to reduce certain aspects of the immune function, such as inflammation. Moreover, this hormone follows a robust circadian rhythm, which peaks 30 min after awakening, termed the Cortisol Awakening Response—CAR, and gradually declines throughout the day.  

The circulating pro-inflammatory cytokines Interferon Gamma (IFN-γ), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-12 (IL-12) and Tumor Necrosis Factor (TNF-α), as well as the anti-inflammatory cytokine Interleukin-10 (IL-10) have been extensively investigated over the past 20 years for their roles in depression, anxiety and various other chronic medical illnesses. Typically, decreases in inflammatory pathway activation during periods without active infection are associated with better physical and mental well-being. That being said, a general decrease in pro-inflammatory (and increase in anti-inflammatory) immune mediators is not necessarily indicative of health and wellness, since acute inflammatory responses are known to be adaptive; instead, a healthy homeostatic balance between pro- and anti-inflammatory signaling is most beneficial. Moreover, chronic inflammatory states can be triggered through psychosocial stress.

The deficits within these factors result in profound impairments in daily functioning, reduced quality of life, an increased risk of suicide, and a substantial lack of productivity. It is clear that there is a dire need to come up with alternative treatments for depression, next to the conventional first-line psycho- and pharmaco-therapies. One such alternative therapeutic strategy is meditation.

How meditation can alleviate the symptoms of depression ~ a biological standpoint

Mindfulness meditation is already being used in certain mental health facilities under different forms of psychotherapeutic intervensions, such as mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT). These usually consist of sessions guided by a professional in addition to at-home practice, over a duration of several weeks. While MBSR is tailored to the management of stressful situations, MBCT involves strategies for dealing with maladaptive thought patterns, which makes it more suitable for the prevention of depressive relapse. Upon repeated training, mindfulness meditation can lead to relatively global cognition-enhancing effects, as shown in Figure 2.

FIGURE 2 | A model of possible effects of mindfulness meditation on psychological and biological deficiencies associated with major depressive disorder; rounded square-shaped box, deficient factor(s) in depression; arrow-shaped box, unidirectional effect; white box, psychological factor/ effect; gray box, biological factor/effect; black arrow, interdependence; BDNF, brain-derived neurotrophic factor.
Adapted from Heuschkel and Kuypers (2020)

Meditative practices based on stress-reduction mechanisms and psychophysiological self-regulation are associated with anti-inflammatory benefits, through their modulation of inflammatory and HPA axis activities. In a study by Cahn et al. (2017), thirty-eight individuals participated in a 3-month yoga and meditation retreat, and were assessed before and after the intervention for psychometric measures, BDNF levels, circadian salivary cortisol levels, and pro- and anti-inflammatory cytokines. Participation in this yoga and meditation retreat was associated with better coping with stress, also known as stress resilience, as well as decreased self-reported depression, increased mindfulness, and generally enhanced well-being. The plasma levels of BDNF were increased by three fold post-retreat compared to pre-retreat, and this increase was inversely correlated with participants’ self-reported anxiety levels on a questionnaire (the Brief Symptom Inventory-18, BSI-18). In addition, the CAR levels were also significantly higher in these participants after the retreat, indicating improvements in the dynamic rhythmicity of the HPA axis activity, which is a marker of better stress resilience.

The researchers also found an unusual pattern of increases in both anti-inflammatory IL-10 as well as pro-inflammatory TNF-α, IFN-γ, IL-1β, IL-6, IL-8, with simultaneous decreases in the pro-inflammatory IL-12. While overall there are inconsistencies across studies on the influence of meditative practices on the immune system, it is also important to bear in mind that these studies tend to differ with respect to the type of intervention (e.g., Kundalini yoga vs. MBSR vs. Tai Chi), population (e.g., clinical vs. non-clinical), setting, design and other methodological factors; these differences lead to complexities involved in interpreting cytokine and other biomarker samples.

Having said that, pro- and anti-inflammatory response modulations may be adaptive depending on the context, for instance in chronically inflamed body states versus non-inflamed healthy normals. It is likely that in relatively healthy adults, intense yogic and meditative practices recruit an integrate brain-body response, resulting in enhanced pro- and anti-inflammatory signaling processes, which on the one hand support an upregulated vigorous immunological surveillance system, while on the other hand concomitantly promote high expression of the anti-inflammatory ‘‘break’’ such as IL-10.

Overall, the biological findings in the above-mentioned study correlate with enhanced stress resilience and well-being. At the end of an intensive three-month yoga-meditation retreat, the increased BDNF signaling and increased CAR were likely related to improved neurogenesis and/or neuroplasticity, and to enhanced alertness and readiness for mind-body engagement, respectively, while the higher levels of anti- and pro-inflammatory cytokines suggested better immunological readiness. Further research should attempt to investigate the role of other contextual factors (e.g., social dynamics, diet, natural environment, relative impact of a revered spiritual teacher etc.) impacting the expression and regulation of these biological processes.

To conclude, it is evident that meditation exerts beneficial effects on the brain. Particularly important to mental disorders, when meditation is used as a therapeutic intervention, it contributes to improving mental states and cognitive abilities by influencing several key biological factors crucial for normal brain functioning.

References

  • Cahn, B.R., Goodman, M.S., Peterson, C.T., Maturi, R., Mills, P.J. (2017). Yoga, Meditation and Mind-Body Health: Increased BDNF, Cortisol Awakening Response, and Altered Inflammatory Marker Expression after a 3-Month Yoga and Meditation Retreat. Front Hum Neurosci, 11:315. doi: 10.3389/fnhum.2017.00315
  • Dutta, A., McKie, S., Downey, D. et al. (2019). Regional default mode network connectivity in major depressive disorder: modulation by acute intravenous citalopram. Transl Psychiatry 9, 116. doi: org/10.1038/s41398-019-0447-0
  • Heuschkel, K., & Kuypers, K.P.C. (2020). Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review. Front. Psychiatry, 11:224. doi: 10.3389/fpsyt.2020.00224
  • Zeidan, F., Johnson, S., Diamond, B., David, Z., & Goolkasian, P. (2010). Mindfulness meditation improves cognition: Evidence of brief mental training. Consciousness and Cognition, 19, 597-605. doi: org/10.1016/j.concog.2010.03.014

The biology of meditation. How meditating can change your brain

Many of us are already familiar with what it means to meditate, in a broad sense, and we have often heard that meditation can improve our lives. Several books and articles have been written on the positive effects exerted by meditation on our bodies and minds. But what is the nature of meditation and how can it help us improve our mental states? More specifically, what happens at the level of neural networks, brain cells and molecules that results in all these beneficial actions upon meditating?

This being human is a guest house. Every morning a new arrival. A joy, a depression, a meanness, some momentary awareness comes as an unexpected visitor. Welcome and entertain them all! […] The dark thought, the shame, the malice. Meet them at the door laughing and invite them in. Be grateful for whatever comes. Because each has been sent as a guide from beyond.

The Guest House by Rumi. Translation by Coleman Barks

FIGURE 1 |Sigiriya rock located near the Dambulla town, in the Central Province, Sri Lanka. Own image.

An introduction to meditation ~ its styles and purposes

Meditation encompasses various emotional and attentional regulatory practices, which aim at improving an individual’s cognitive abilities. Many recent behavioral, electroencephalographic and neuroimaging studies have investigated the neuronal events related to meditation, in order to achieve an increased understanding of cognitive and affective neuroplasticity, attention and self-awareness, as well as for their possible clinical implications.

The video below shows the kind of brain changes meditation leads to, in a monk who is a long-term practitioner.

According to Raffone and Sirivasan (2010), a central feature of meditation is the regulation of attention, and as such, meditation practices can be classified into two main styles—focused attention (FA) and open monitoring (OM)—depending on how attentional processes are directed. While the FA (‘concentrative’) style is based on focusing attention on a given object in a sustained manner, the second style, OM (‘mindfulness-based’) meditation, involves the non-reactive monitoring of the content of ongoing experience. More specifically, mindfulness refers to being constantly aware of the way we perceive and monitor all mental processes, including perceptions, sensations, cognitions and affects.

FA meditation techniques imply, apart from sustaining the attention on an intended object, monitoring attentional focus, detecting distraction, disengaging attention from the source of distraction, and (re)directing attention (back) on the object. This kind of attentional stability and vividness is achieved through concentrated calmness or serene attention, denoted by the word Samatha (which literarily means quiescence) in the Buddhist contemplative tradition. Another technique which can be broadly included in the FA meditation is transcendental meditation, which centers on the repetition of a mantra.

Unlike FA meditation, OM meditation does not involve an explicit attentional focus, and therefore does not seem to be associated with brain areas that control sustained or focused attention. Instead, OM meditation engages brain regions implicated in vigilance, monitoring and detachment of attention from sources of distraction from the ongoing stream of experience. Therefore, OM meditation is based on detecting arising sensations and thoughts within an unrestricted ‘background’ of awareness, without a ‘grasping’ of these events in an explicitly selected focus. In the transition from a FA to an OM meditative state, the object as the primary focus is gradually replaced by an ‘effortless’ sustaining of an open background of awareness, without an explicit attentional selection. In the Buddhist tradition, the practice of Vipassana (insight) OM meditation requires, first of all, attentional stability and vividness (acuity), as developed in FA meditation, in order to achieve a deep and reliable introspection.

The ancient yogic practice of Yoga Nidra, which is less-known, and yet is becoming increasingly popular, can also fall into the category of OM meditation. It is said to reduce stress and improve sleep, and that it has the potential to engender a profound sense of joy and well-being.

Another type of OM meditation worth mentioning here is the loving-kindness meditation or non-referential compassion (also known as Mettā in the Pali language), which involves compassion-based mental training aimed at promoting empathy. Practicing this kind of meditation is believed to increase the capacity for forgiveness, connection to others and self-acceptance, and to boost well-being and reduce stress. For more detailed descriptions as well as a deeper and broader understanding of the neurological implications of these different meditation practices, I strongly encourage you to check out the reviews listed in the Reference section, especially Brandmeyer et al. (2019) and Raffone & Srinivasan (2010).

Of all these different kinds, mindfulness meditation, which originally stems from Buddhist meditation traditions, has received the most attention in neuroscience research over the last twenty years.

Research over the past two decades broadly supports the claim that mindfulness meditation — practiced widely for the reduction of stress and promotion of health — exerts beneficial effects on physical and mental health, and cognitive performance. 

Tang et al. (2015)

Sustained engagement with mindfulness meditative practices has been shown to have neurophysiological and psychological benefits. In healthy individuals, several months of mindfulness meditation practice correlates with improvements in self-regulation and subjective well-being. Even much shorter mindfulness meditation training, of a few days, has a positive impact on mood and executive functioning, while at the same time reducing fatigue and anxiety.

Brain structural changes following mindfulness meditation

Several recent studies have investigated the structural changes in the brain related to mindfulness meditation, and have reported alterations in cortical thickness, hippocampal volume, and grey-matter volume and/or density. However, before we dive into how meditation can change our brains, it should be mentioned that there are a few issues with the current state of meditation research. First of all, most of these studies have made cross-sectional comparisons between experienced meditators and controls. But only a few recent studies have investigated longitudinal changes in novice practitioners. These logitudinal studies are very important because they follow subjects over a long-term period of practice, and are thus able to determine whether changes induced by meditation training persist in the absence of continued practice. Therefore, more such studies would be required for a complete picture of the effects of meditation on mental health.

In addition, the studies on mindfulness meditation so far have generally included small sample sizes, of between 10 and 34 subjects per group, which leads to limitations in interpreting the results, as well as increases the chances of false-positives. Another prossible issue is that these studies use different research designs, measurements and type of mindfulness meditation. Hence, it comes as no surprise that the reported effects of meditation are diverse and cover multiple regions in the brain, including the cerebral cortex, subcortical grey and white matter, brain stem and cerebellum. That being said, these findings can also reflect the fact that the effects of meditation involve large-scale and interactive brain networks.

According to various fMRI studies, minfulness meditation exerts its effects primarily (though not exclusively) on a network of brain regions – the Default Mode Network (DMN). This network comprises structures in the medial prefrontal cortex (PFC), posterior cingulate cortex (PCC), anterior precuneus and inferior parietal lobule, which have been previously shown to have high activity during rest, mind wandering and conditions of stimulus-independent thought. These regions have been suggested to support different mechanisms by which an individual can ‘project’ themselves into another perspective.

When comparing meditators with naïve subjects, DMN regions, such as the medial PFC and PCC, have shown much less activity in meditators, across different types of meditation. This has been interpreted as indicating diminished self-referential processing. Experienced meditators also seem to exert stronger coupling between the PCC, dorsal anterior cingulate cortex (ACC) and dorsolateral PFC, both at baseline and during meditation, which indicates stronger cognitive control over the function of the DMN.

Brewer et al. (2011) investigated brain activity in experienced meditators versus meditation-naïve controls as they performed several different mindfulness meditations (Concentration, Loving-Kindness, Choiceless Awareness). They found that the main nodes of the DNM (medial PFC and PCC) were relatively deactivated in experienced meditators across all meditation types (Figure 2). Moreover, functional connectivity analysis revealed increased coupling in experienced meditators between the PCC, dorsal ACC, and dorsolateral prefrontal cortices, both at baseline and during meditation, as seen in Figure 3. This increased connectivity with medial PFC regions supports greater access of the default circuitry to information about internal states, because this region is also highly interconnected with limbic regions (such as insula and amygdala).

FIGURE 2 | Experienced meditators demonstrate decreased DMN activation during different meditation conditions: Choiceless Awareness (green bars), Loving-Kindness (red), and Concentration (blue) meditations. The decreased activation in PCC in meditators is common across different meditation types. Brain activation in meditators > controls is shown, collapsed across all meditations, relative to baseline (A and B). Activations in the left mPFC and PCC (C and D). Taken from Brewer et al. (2011)

FIGURE 3 | Experienced meditators show coactivation of mPFC, insula, and temporal lobes during meditation. Differential functional connectivity with mPFC seed region and left posterior insula is shown in meditators > controls: (A) at baseline and (B) during meditation. (C) Connectivity z-scores (±SD) are shown for left posterior insula. Choiceless Awareness (green bars), Loving-Kindness (red), and Concentration (blue) meditation conditions. Taken from Brewer et al. (2011)

Meditators also reported significantly less mind-wandering, which has been previously associated with activity in the DMN. Therefore, these results demonstrated that alterations in the DMN are related to reduction in mind-wandering. They also suggested that meditation practice may transform the resting-state experience into one that resembles a meditative state – a more present-centered default mode.

The findings from this study have several clinical implications, given that a number of pathological conditions have been associated with dysfunction within areas of the DMN, including depression. The self-referrential function of the DMN has pointed to the possibility that excessive rumination (negative inner preoccupation about the personal past, present and future) in depression involves excessive DMN activity as well as an inability to switch out of it, in response to external demands. Mindfulness meditation may prove useful in reducing distractive and ruminative thoughts and behaviors, and this ability may provide a unique mechanism by which mindfulness meditation reduces distress and improves mood.

In addition, meditation has also been shown to promote neuroplasticity, an important neuronal process that entails structural and functional brain adaptations in response to changes in environmental conditions. A key neurotrophin that promotes neuroplasticity is the brain-derived neurotrophic factor (BDNF), which is usually found in abnormally low levels in various psychiatric and neurological disorders. Meditation has been shown to increase the levels of BDNF, thus promoting neuronal development, survival and plasticity, which in turn contribute to restoring the normal functioning of brain networks.

In sum, there is emerging evidence that mindfulness meditation might trigger neuroplastic changes in brain regions involved in the regulation of emotion and cognition. Although, as mentioned earlier, these studies often suffer from low methodological quality and present with speculative post-hoc interpretations, this is quite common in a new field of research. Thus, further research needs to use longitudinal, randomized and actively controlled research designs and larger sample sizes, as well as to concentrate on the biological factors implicated in mental health, in order to advance the understanding of how mindfulness meditation interacts with the brain. If supported by rigorous research, the practice of mindfulness meditation might be a promising therapeutic approach for clinical disorders, such as depression, and might facilitate the cultivation of a healthy mind and improved well-being.

For the readers interested in the effects of meditation on depression, please visit my article The biological implications of meditation practices in the treatment of depression.

References

  • Brandmeyer, T., Delorme, A., Wahbeh, H. (2019). Chapter 1 – The neuroscience of meditation: classification, phenomenology, correlates, and mechanisms, Editor(s): Narayanan Srinivasan, Progress in Brain Research, Elsevier, 244: 1-29. doi: org/10.1016/bs.pbr.2018.10.020
  • Brewer, J.A., Worhunsky, P.D., Gray, J.R., Tang, Y.Y., Weber, J., Kober, H. (2011). Meditation experience is associated with differences in default mode network activity and connectivity. Proc Natl Acad Sci U S A, 108(50):20254-9. doi: 10.1073/pnas.1112029108
  • Kabat-Zinn, J. (2003). Mindfulness-based interventions in context: past, present, and future. Clin Psychol Sci Pract 10:144–156
  • Heuschkel, K., & Kuypers, K.P.C. (2020). Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review. Front. Psychiatry, 11:224. doi: 10.3389/fpsyt.2020.00224
  • Raffone, A., & Srinivasan, N. (2010). The exploration of meditation in the neuroscience of attention and consciousness. Cognitive Processing, 11:1-7. doi: 10.1007/s10339-009-0354-z.
  • Tang, Y.Y., Hölzel, B.K., Posner, M.I. (2015). The neuroscience of mindfulness meditation. Nat Rev Neurosci, 16(4):213-25. doi: 10.1038/nrn3916
  • Zeidan, F., Johnson, S., Diamond, B., David, Z., & Goolkasian, P. (2010). Mindfulness meditation improves cognition: Evidence of brief mental training. Consciousness and Cognition, 19, 597-605. doi: org/10.1016/j.concog.2010.03.014.