Neuroinflammation: The causes, treatment and how it contributes to depression.

Depression, anxiety, ADHD, addiction, obsessive compulsive disorder and neurodegenerative diseases such as Alzheimer’s share common links which include immune activation and resulting neuroinflammation as potentially causative factors (1). Neuroinflammation is defined as inflammation of the brain and central nervous system, and it may be responsible for a large part of global mental health burden. It is the brain’s response to disrupted homeostasis, or equilibrium.

Some level of neuroinflammation is helpful to resist pathogens and promote early brain development. However, when the inflammatory response does not switch off, inflammation turns from acute (short term) to chronic (long term) and could be likened to a fire that simmers away, but never goes out.

Obesity,  inadequate dietary intake of antioxidants and healthy fats, lack of exercise and chronic stress contribute to the development of neuroinflammation due to disruptions in metabolic homeostasis. In addition, untreated infection via pathogens, oxidative stress, high blood sugar levels, and other chronic inflammatory health conditions contribute to the development of neurological imbalances. Inflammation caused by these aberrations of normal functioning of the human body results in neurotransmitter dysregulation, neuron dysfunction, poor neurite outgrowth and reduction in the growth of new brain cells (4).

How does inflammation affect brain health?

Inflammation can affect brain health in a variety of different ways: It disrupts neurotransmitter receptor response and transmission (affecting mood, sleep, and movement), and neuronal plasticity/growth (including memory, cognition and learning). Studies have linked oxidative stress and resulting neuroinflammation to depression, anxiety, cognitive decline, schizophrenia, and even post-traumatic stress disorder (2).

In addition, research meta-analyses have revealed that inflammatory markers are often increased in those suffering from disorders such as major depression, including tumour necrosis factor alpha, interleukin-6, and C-reactive protein (4). It is suggested that this response precedes depressive symptoms, not vice versa, and that increased inflammatory markers during childhood are strong predictors for risk of depression in later life.

Does neuroinflammation start in the gut?

The gut-brain connection is an incredibly important factor when considering brain and whole-body health. The microbiome literally “talks” to the brain and is a whole organ unto itself. The inflammatory response begins in the gut when tight junctions between gastrointestinal cells open in response to allergens or inflammatory foods such as gluten and dairy. This allows tiny food particles and the products of digestion to leak out of the gut and into the bloodstream, activating the immune system and causing a chain reaction throughout the rest of the body.

Improving gut health positively affects symptoms of many conditions, including those of the brain. For example, certain strains of probiotics have been shown to improve symptoms of anxiety and depression (3). A lack of microbial diversity can contribute to the development and maintenance of mental disorders, with some strains of probiotics shown to reduce psychological symptoms of distress and reduce urinary cortisol (5). Links also exist between the pathology of ‘leaky gut’ and major depressive disorder, adding to the evidence that depression is not a purely ‘brain-related’ condition.

Stress produces inflammation and worsens symptoms of depression.

Research has shown repeatedly that stress negatively affects symptoms of depression. In a study examining medical students, stress was shown to increase depressive symptoms by an average of 173% (6). Unfortunately, chronic stress also increases inflammatory response throughout the body via the hypothalmic-pituitary-adrenal axis (HPA) which, when chronically stimulated, results in cellular glucocorticoid resistance and an upregulation of the chemical messengers that increase inflammatory processes (proinflammatory cytokines). The HPA axis is responsible for our “flight or fight” response, but was never meant to be activated for long periods of time. Acute or short-lived periods of stress are usually beneficial, because they force the body to adapt, but chronic or long-term stress results in damage and dysregulation over time. In effect, disorders such as depression and anxiety appear to be the result of the body’s attempts to adapt to long-term stress.

How to support brain health with diet and lifestyle

How we nourish or don’t nourish our bodies has serious implications for present and future health. Western diets often lack nutrients essential for wellbeing, while creating an excess of others. A diet high in sugar, processed food, while also lacking fruits, vegetables, good fats and protein seriously disrupts our metabolism and damages both body and brain. A recent study highlighted the relationship between consuming higher amounts of added sugars and an increased risk of depression (7).

Supporting your brain with diet  is one of the simplest changes you can make to positively influence its health. Essential fatty acids from fish, nuts, oils and avocados are perfect ‘neural nourishment’, while consuming a rainbow of fruits and vegetables provides a wealth of phytonutrients that promote antioxidant production. A recent study found that those who ate 2-3 servings of green vegetables a day, were found to be 11 years younger (cognitively speaking), than the control group who did not (9).

Along with nutrition, daily exercise, meditation, and taking time out for self is also of vital importance to help reduce inflammation, stress and create balance. A 2016 study highlighted how a group of experienced meditators showed reduced inflammatory and cortisol response when subjected to stress tests, in comparison to their non-meditating counterparts (8). Even just 2 minutes twice a day is beneficial in lowering stress and calming the mind.

Recent studies have found that regular exercise reduces inflammatory markers, corresponding to a reduction in depressive symptoms (10). Exercise also stimulates the production of a substance known as BDNF (brain derived neurotrophic factor), which assists in improving synaptic connections, increasing neuron outgrowth and stimulating the growth of new brain cells (11).

Lifestyle changes are powerful when it comes to supporting the health of the central nervous system. Avoiding sugars, processed foods, and consuming a whole-food based diet provides both body & brain with the nutrition it needs to thrive. Exercise, relaxation and taking the time to be involved with community are all effective means of connecting with self and those around us, reducing the effects of stress and supporting mental and emotional wellbeing.

If you’d like to learn more about neuroinflammation, or how best to support brain health, please feel free to contact us.


(1) Ransohoff, R. M., Schafer, D., Vincent, A., Blachère, N. E., & Bar-Or, A. (2015). Neuroinflammation: Ways in Which the Immune System Affects the Brain. Neurotherapeutics, 12(4), 896–909.

(2) Miller, M. W., & Sadeh, N. (2014). Traumatic stress, oxidative stress, and posttramatic stress disorder: neurodegeneration and the accelerated-aging hypothesis. Molecular Psychiatry, 19(11), 1156–1162.

(3) Liu, R. T. (2017). The microbiome as a novel paradigm in studying stress and mental health. American Psychologist, 72(7), 655–667.

(4) Kiecolt-Glaser, J. K., Derry, H. M., & Fagundes, C. P. (2015). Inflammation: Depression fans the flames and feasts on the heat. American Journal of Psychiatry, 172(11), 1075–1091.

(5) Dinan, T. G., Stanton, C., & Cryan, J. F. (2013). Psychobiotics: A novel class of psychotropic. Biological Psychiatry, 74(10), 720–726.

(6) Fried, E. I., Nesse, R. M., Guille, C., & Sen, S. (2015). The Differential Influence Of Life Stress On Individual Symptoms Of Depression HHS Public Access. Acta Psychiatr Scand, 131(6), 465–471.

(7) Sanchez-Villegas, A., Zazpe, I., Santiago, S., Perez-Cornago, A., Martinez-Gonzalez, M. A., & Lahortiga-Ramos, F. (2017). Added sugars and sugar-sweetened beverage consumption, dietary carbohydrate index and depression risk in the Seguimiento Universidad de Navarra (SUN) Project. British Journal of Nutrition.

(8) Rosenkranz, M.A., Lutz, A., Perlman, D.M., Bachhuber, D.R.W., Schuyler, B.S., Macgoon, D.G., Davidson, R.J. (2016). Reduced stress and inflammatory responsiveness in experienced meditators compared to a matched healthy control group. Psychoneuroendocrinology. 68, 117-125. doi:10.1016/j.psyneuen.2016.02.013

(9) Morris, M. C., Wang, Y., Barnes, L. L., Bennett, D. A., Dawson-Hughes, B., & Booth, S. L. (2018). Nutrients and bioactives in green leafy vegetables and cognitive decline. Neurology, 90(3), e214–e222.

(10) Lavebratt, C., Herring, M. P., Liu, J. J., Wei, Y. Bin, Bossoli, D., Hallgren, M., & Forsell, Y. (2017). Interleukin-6 and depressive symptom severity in response to physical exercise. Psychiatry Research, 252(November 2016), 270–276.

(11) Szuhany, K. L., Bugatti, M., & Otto, M. W. (2015). A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. Journal of Psychiatric Research, 60, 56–64.


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