Neurobiological basis of chiropractic care for major depression

Is there ever a more pertinent time to talk about chiropractic care and depression than eighteen months into a pandemic, when it has been widely reported that many mental health care services are stretched to capacity? While there is a litany of research on cognitive behavioural therapy and anti-depressant medication in the treatment of depression, recent research has emerged indicating that there is more to the picture than these modes of care alone. There are indications that depression may have inflammatory and immune-related aspects and that gut health is an important consideration for depression patients [1-6]. Now, a new study has emerged examining the neurobiological basis for chiropractic care in cases of depression.

While this research synthesizes a large amount of information into one narrative review, it is important to note that this does not discourage talk therapy or anti-depressant medication. It simply argues that chiropractic care can assist with the nervous system heavy aspects of the major depressive disorder. And these, it seems, make up the majority of the symptoms.

Currently, the World Health Organisation lists Major Depressive Disorder (MDD) as the fourth main cause of disability worldwide [7]. In the recent paper, carried in the journal Acta Medica, a substantial literature review was undertaken examining the impact of chiropractic and depression on the nervous system. The results, the authors state, indicate that, “Chiropractic and spinal manipulative therapies along with vagal nerve stimulation may therefore be regarded as treatment options for depression” [8].

So how then are the two linked?  As the article points out, depression is known to cause severe mental distress, as well as autonomic nervous system (ANS) and endocrine dysfunction (though the latter two are talked about much less frequently). While the literature review goes into great detail on each of the neurobiological aspects of depression and ANS function (you can read it at the reference below), here’s the scoop!

 

The Autonomic Nervous System in Depression

The vagus nerve is one of ten major cranial nerves, and is an object of some medical and therapeutic fascination at this point in time. It runs behind the ear and down the neck and has significant roles in modulating function of the heart, lungs and gut among other things tied up in the parasympathetic nervous system.

In simple terms, the sympathetic division of the autonomic nervous system is our fight / flight / freeze survival mechanisms, and the parasympathetic division contains all our rest / digest / reproduce and repair mechanisms. These all happen automatically, below the level of conscious thought. ANS dysfunction includes loss of vagal tone or parasympathetic activation, and over reactivity of sympathetic nervous system.  So, when a complex condition like depression impacts autonomic nervous system function in favour of the sympathetics, we can see cross over between MDD symptoms and the firing of our sympathetic nervous system. These include anxiety, continuous depressed mood, anhedonia, poor concentration, feelings of guilt, loss of appetite, insomnia and even suicidal ideation.

According to the article, ANS dysfunction may also contribute to commonly observed major depression comorbidities including coronary heart disease and osteoporosis. Other research (preclinical studies) have identified several neurotrophic factors are involved in the pathogenesis of MDD.

While it might seem like a big leap to make, these indications have been hidden in basic science for a long time. Making the links and caring for the whole person instead of isolating Major Depressive Disorder to being a “mental thing” is where we can make the difference.

The literature review unearths a number of factors that link MDD and the nervous system which chiropractors care for. One such factor is brain-derived neurotrophic factor (BDNF). It is an important neural growth factor that regulates neuronal maturation, neurogenesis, synaptic plasticity and survival. How might this look in the case of depression (according to the authors of the literature review) [8]?

• Reduced BDNF levels have been observed in the prefrontal cortex and hippocampus of stressed animals, suicidal subjects and depression patients. Inadequate levels of BDNF can be improved by treatment with anti-depressants and physical therapy in depressed patients and animal models. While chiropractic hasn’t been examined in conjuction with BDNF in this paper, it is certainly worth further investigation especially given the impact of physical therapy on depression.
• Nerve growth factor (NGF) is another important neurotrophin. Nerve growth factor acts as a modulator of the hypothalamic-pituitary-adrenal axis and contributes to maintaining the neuroendocrine and immune systems. Many studies have observed functional abnormalities of the hypothalamic-pituitary-adrenal axis in MDD. This axis is important in firing up our sympathetics (fight / fight / freeze survival mechanisms and is thus important when recognising the ongoing effects of ANS dysfunction and depression.
• NGF proved to have antidepressant properties, while acute and chronic stress reduced NGF expression, an effect that is reversed by antidepressant treatment.

With this being the case, where does chiropractic fit in? Chiropractors often say that the cause of subluxations are trauma, toxins and stress. So therefore, the links to sympathetic function and chronic stress already seem obvious. But the article has far more to say on the topic [8].

The Chiropractic Picture:

Chiropractic works on the nervous system, stimulating it to release various chemicals and hormones that regulate blood pressure and flow, calm the brain and reduce inflammation [8]. Within that nervous system lies the vagus nerve. Research indicates that vagus nerve stimulation may influence cell differentiation and survival through BDNF expression, which is low in most mood disorders like MDD, and antidepressant treatments increase its levels [8].  According to the literature review, substantial improvements in MDD can be observed after 3-12 months of vagal nerve stimulation therapy [8].

So basically, “vagal nerve stimulation acts on the same brain regions, signal transduction mechanisms and neurotransmitters as conventional antidepressants, and has similar effects, which however take longer to manifest [8].

Vagus nerve stimulation has been a hot topic in chiropractic and other health care circles for some time now, with polyvagal theory making its way to hot topic list as the big thinkers explore how chiropractic’s known ability to stimulate the Vagus nerve may relate to clinical outcomes. Indeed, it is an exciting area of study even outside of chiropractic circles as Vagus nerve stimulation is harnessed in the treatment of diseases like epilepsy. While there is much yet to confirm and explore in future research before we can confidently make big claims, it is still a promising area of scientific exploration.

We know that chiropractic research has indicated the many benefits of care when it comes to chronic back and neck pain. It is also well documented in literature that chronic pain and depression are frequently observed in the same patients.  Interestingly, a likely explanation for this correlation is their common neurological pathways. In fact, 50-65% of patients with chronic pain are also diagnosed with depression.

The authors noted that “Major depression may depend largely on imbalances in autonomic nervous system activity. All symptoms of depression, such as high cortisol, high adrenalin, insomnia, agitation and anxiety, can be attributed to excessive activity of the sympathetic system. Furthermore, neuroendocrine factors like dopamine, BDNF and NGF have roles in the pathophysiology of MDD. Although not yet definitely confirmed, chiropractic therapy and vagal nerve stimulation may possibly regulate the autonomic nervous system through activation of the parasympathetic nervous system, reduction of sympathetic nervous system activity, and synthesis of neuroendocrine factors [8].”

While there is always room for more research, and further exploration in terms of solidifying the links between chiropractic care and depression outcomes, this review offers up a huge amount of data in a neatly wrapped narrative review. Best of all, it offers hope to depression sufferers that chiropractic care may add to the management of their major depressive disorder.

We can’t wait to see what else emerges from this line of investigation.

 

REFERENCES:

1. Himmerich. H., Fulda. S., Linseisen. J., Seiler. H., Wolfram. G., Himmerich. S., Gedrich. K., Kloiber. S., Lucae. S., Ising. M., M.Uhr. M., Holsboer. F., Pollmächer. T., (2008), “Depression, comorbidities and the TNF-α system”, European Psychiatry, 23(6): 421-429, https://doi.org/10.1016/j.eurpsy.2008.03.013
2. Sahin. T. D., S., Karson. A., Balcı. F., Yazır. Y., Bayramgürler. D., Utkan. T., (2015), “TNF-alpha inhibition prevents cognitive decline and maintains hippocampal BDNF levels in the unpredictable chronic mild stress rat model of depression”, Behavioural Brain Research, 292(1): 233-240, https://doi.org/10.1016/j.bbr.2015.05.062
3. Fasicka. V., Spengler. R. N., Samankana. S., Nader. N. D., Ignatowski. T. A., (2015),  “The hippocampus and TNF: Common links between chronic pain and depression”, Neuroscience and Biobehavioral Reviews, 53:139-159, https://doi.org/10.1016/j.neubiorev.2015.03.014
4. Song. X., Huang. Z., Song. W. B., Song. X., Fuhr. A. F., Rosner. A. L., Ndtan. H., Rupert. R. L., (2016), “Attenuation effect of spinal manipulation on neuropathic and postoperative pain through activation endogenous anti inflammatory cytokine interleukin 10 in rat spinal cord”, Journal of Manipulative and Physiological Therapeutics, 31(1): 42-53, https://doi.org/10.1016/j.jmpt.2015.12.004
5. Teodorczyk-Injeyan. J. A., Injeyan. S., Ruegg. R., (2006), “Spinal manipulative therapy reduces inflammatory cytokines but not substance P production in normal subjects”, Journal of Manipulative and Physiological Therapeutics, 29(1): 14-21, https://doi.org/10.1016/j.jmpt.2005.10.002
6. Mohammadian. P., Gonsalves. A., Tsai. C., Hummel. T., Carpenter. T., (2004), “Areas of Capsaicin-Induced Secondary Hyperalgesia and Allodynia Are Reduced by a Single Chiropractic Adjustment: A Preliminary Study”, Journal of Manipulative and Physiological Therapeutics, 23(6): 381-387, https://doi.org/10.1016/j.jmpt.2004.05.002
7. Gold PW, Machado-Vieira R, Pavlatou MG (2015). Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. Neural Plast. 2015; 2015():581976.
8. Kiani, A. K., Maltese, P. E., Dautaj, A., Paolacci, S., Kurti, D., Picotti, P. M., & Bertelli, M. (2020). Neurobiological basis of chiropractic manipulative treatment of the spine in the care of major depression. Acta bio-medica : Atenei Parmensis, 91(13-S), e2020006. https://doi.org/10.23750/abm.v91i13-S.10536