Source: https://www.mindhealth360.info/contributor/inflammation/
Timestamp: 2019-04-23 14:35:46+00:00

Document:
The word “inflammation” comes from the Latin word “inflammare” which means “to kindle or set on fire”. The inflammatory response consists of redness, heat, and swelling, either internal or external, and is the normal response of living tissue to injury or infection.Rankin, J. A. (2004). Biological Mediators of Acute Inflammation. [online] AACN Clinical Issues, 15 (1), pp. 3–17. Available at: https://www.ncbi.nlm.nih.gov/pubmed/14767362 [accessed 1 Nov. 2017].
Inflammation is a complicated process involving more than just the activation of the immune response. It has a diverse effect on many organs of the body, including the brain.Perlmutter, D. and Colman, C. (2004). The Better Brain Book. New York: Riverhead Books, pp. 183-4.
The association between the immune system and mental health has been formally acknowledged since at least the 1970s and is an area of increasing research.
The term ‘psycho-neuroimmunology’ was developed in the 1970s to describe the association between the brain, behaviour and the immune system.
The term is increasingly relevant, as it examines mental health issues from the perspective of the immune system, the gut, and the nervous system, as well as looking at other organs in the body.
Many diseases, from rheumatoid arthritis and diabetes to cancer and heart disease are caused by, or correlated with inflammation. Often the exact cause of inflammation is difficult to isolate.Tabas, I. and Glass, C. K. (2013). Anti-inflammatory therapy in chronic disease: challenges and opportunities. [online] Science, 339 (6116), pp. 166-72. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23307734 [accessed 1 Nov. 2017].
There is growing evidence that inflammation also plays an important role in mood disorders and other mental health conditions,Perlmutter, D. and Colman, C. (2004). The Better Brain Book. New York: Riverhead Books, pp. 183-4. possibly through its activation of the immune system.
The underlying process for this is often some form of neuro-inflammation – which is an immune-related process that occurs within the brain, creating inflammation there.Wohleb, E. and Godbout, J. (2013). Basic Aspects of the Immunology of Neuroinflammation. Modern Trends in Pharmacopsychiatry, 28, pp. 1-9. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25224887 [accessed 1 Nov. 2017].
Neuro-inflammation can be caused by traumatic brain injuries (for example in a car accident) or are correlated with brain infections or autoimmune disease.
In these circumstances, activated central nervous system (CNS) immune cells and the blood-brain barrier (BBB) coordinate the production of cytokines — chemicals involved in inflammation, and other chemical messengers — which directly influence brain function and act on specific receptors of the brain.Wohleb, E. and Godbout, J. (2013). Basic Aspects of the Immunology of Neuroinflammation. Modern Trends in Pharmacopsychiatry, 28, pp. 1-9. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25224887 [accessed 1 Nov. 2017].
Chronic neuro-inflammation, is implicated in neurodegenerative disease such as Alzheimer’s disease and declines in cognitive function.
There is strong evidence linking depression to inflammation, Diniz, B. S., Butters, M. A., Albert, S. M., Dew, M. A. and Reynolds, C. F. (2013). Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. [online] The British Journal of Psychiatry, 202 (5), pp. 329–335. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23637108 [accessed 1 Nov. 2017]. though it’s not clear whether inflammation contributes to depression, or whether depression contributes to inflammation.
Studies demonstrate that, when compared to non-depressed patients, depressed patients consistently demonstrate all the cardinal features of inflammation Miller, A. H., Maletic, V. and Raison, C. L. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. [online] Biological Psychiatry, 65(9), pp. 732–741. Available at: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01532-1/fulltext [accessed 1 Nov. 2017].
Lypopolysaccharides (LPS) which are components of bacteria in the gut, are one of the major causes of inflammation. LPS can get into the bloodstream when there is leaky gut, and can cause systemic inflammation, where it can cause behavioural symptoms overlapping with those of major depression Miller, A. H., Maletic, V. and Raison, C. L. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. [online] Biological Psychiatry, 65(9), pp. 732–741. Available at: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01532-1/fulltext [accessed 1 Nov. 2017].
There is also a link between depression, inflammation and oxidative pathways. Inflammation and oxidation are often seen as ‘essential partners’ in mental health issues.Parletta, N., Milte, C. M. and Meyer, B. J. (2013). Nutritional modulation of cognitive function and mental health. [online] The Journal of Nutritional Biochemistry, 24 (5), pp. 725–43. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23517914 [accessed 1 Nov. 2017].
Depression is associated with a chronic, low-grade inflammatory response Rawdin, B. J., Mellon, S. H., Dhabhar, F. S., Epel, E. S., Puterman, E., Su, Y., … Hamilton, S. P. (2013). Dysregulated relationship of inflammation and oxidative stress in major depression. [online] Brain, Behavior, and Immunity, 31, pp. 143–52. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23201587 [accessed 1 Nov. 2017]., Berk, M., Williams, L. J., Jacka, F. N., O’Neil, A., Pasco, J. A., Moylan, S., … Byrne, M. L. (2013). So depression is an inflammatory disease, but where does the inflammation come from? [online] BMC Medicine, 11(1), p. 200. Available at: https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-200 [accessed 1 Nov. 2017].
Depression is associated with elevated cytokines which mediate the body’s innate immunity and their receptors in blood and cerebrospinal fluid (CSF) Miller, A. H., Maletic, V. and Raison, C. L. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. [online] Biological Psychiatry, 65(9), pp. 732–741. Available at: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01532-1/fulltext [accessed 1 Nov. 2017].
There is a link between depression and premature mortality in chronic diseases such as cancer and heart disease Fagundes, C. P., Glaser, R., Hwang, B. S., Malarkey, W. B. and Kiecolt-Glaser, J. K. (2013). Depressive Symptoms Enhance Stress-induced Inflammatory Responses. [online] Brain, Behavior, and Immunity, 31, pp. 172–6. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518610/ [accessed 1 Nov. 2017].
Depression is associated with an increase in inflammatory markers such as acute phase proteins, chemokines, adhesions molecules and anti-inflammatory mediators such as prostaglandins Miller, A. H., Maletic, V. and Raison, C. L. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. [online] Biological Psychiatry, 65(9), pp. 732–741. Available at: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01532-1/fulltext [accessed 1 Nov. 2017].
Depression activates cell-mediated immunity (the part of the immune system not associated with antibodies and which is known as the body’s adaptive immunity) Miller, A. H., Maletic, V. and Raison, C. L. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. [online] Biological Psychiatry, 65(9), pp. 732–741. Available at: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01532-1/fulltext [accessed 1 Nov. 2017].
Activation of cell-mediated immunity refers to activation of the T-cells of the immune system Berk, M., Williams, L. J., Jacka, F. N., O’Neil, A., Pasco, J. A., Moylan, S., … Byrne, M. L. (2013). So depression is an inflammatory disease, but where does the inflammation come from? [online] BMC Medicine, 11(1), p. 200. Available at: https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-200 [accessed 1 Nov. 2017]., Rawdin, B. J., Mellon, S. H., Dhabhar, F. S., Epel, E. S., Puterman, E., Su, Y., … Hamilton, S. P. (2013). Dysregulated relationship of inflammation and oxidative stress in major depression. [online] Brain, Behavior, and Immunity, 31, pp. 143–52. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23201587 [accessed 1 Nov. 2017].
Research has provided evidence for depression-inflammation relationships developing early in life. There appears to be a circular relationship between depression and inflammation in children.
Children with higher inflammatory cytokine levels were more likely to be depressed at age 18 compared with those with lower cytokine levels Kim, J.-W., Szigethy, E. M., Melhem, N. M., Saghafi, E. M. and Brent, D. A. (2014). Inflammatory markers and the pathogenesis of pediatric depression and suicide: a systematic review of the literature. [online] The Journal of Clinical Psychiatry, 75 (11), pp. 1242-53. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25470085 [accessed 1 Nov. 2017].
C -reactive protein is a marker of inflammation and is raised in infection or inflammation in the body Copeland, W. E., Shanahan, L., Worthman, C., Angold, A. and Costello, E. J. (2012). Cumulative depression episodes predict later C-reactive protein levels: a prospective analysis. [online] Biological Psychiatry, 71(1), pp. 15–21. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22047718 [accessed 1 Nov. 2017].
Evidence shows inflammatory markers were higher in about a third of depressed patients compared to the majority of non-depressed subjects Raison, C. L. and Miller, A. H. (2011). Is depression an inflammatory disorder? [online] Current Psychiatry Reports, 13 (6), pp. 467–75. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21927805 [accessed 1 Nov. 2017].
Behaviour and mood are heavily influenced by neurotransmitters and brain networks.
Cytokines, both pro-inflammatory and anti-inflammatory cytokines, are small proteins released by cells which have a specific effect on the interactions and communications with cells. Zhang, J. M. and An, J. (2007). Cytokines, Inflammation and Pain. [online] International Anesthesiology Clinics, 45 (2), pp. 27-37. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785020/ [accessed 2 Nov. 2017].
Cytokines have been shown to interact with virtually every physiological process relevant to depression, including the processing and function of neurotransmitters.
In research, administering cytokines profoundly affected the production, uptake and release of key neurotransmitters for mood and behaviour, serotonin, noradrenaline and dopamine Miller, A. H., Maletic, V. and Raison, C. L. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. [online] Biological Psychiatry, 65(9), pp. 732–741. Available at: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01532-1/fulltext [accessed 1 Nov. 2017].
Reduced levels of acetylcholine (the neurotransmitter involved in memory and stress) Miller, A. H., Maletic, V. and Raison, C. L. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. [online] Biological Psychiatry, 65(9), pp. 732–741. Available at: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01532-1/fulltext [accessed 1 Nov. 2017].
There seems to be a symbiotic relationship between inflammation and stress hormones in that inflammatory cytokines can trigger the release of stress hormones; and conversely, elevated stress hormones can trigger inflammation.
The administration of inflammatory cytokines acutely impact the HPA axis, which is activated during the stress response Miller, A. H., Maletic, V. and Raison, C. L. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. [online] Biological Psychiatry, 65(9), pp. 732–741. Available at: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01532-1/fulltext [accessed 1 Nov. 2017].
All these stress hormones are increased in patients with depression Miller, A. H., Maletic, V. and Raison, C. L. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. [online] Biological Psychiatry, 65(9), pp. 732–741. Available at: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01532-1/fulltext [accessed 1 Nov. 2017].
Conversely, impairment in the HPA axis activity due to chronic stress and the associated rise in cortisol can cause enhanced susceptibility to inflammation Silverman, M. N. and Sternberg, E. M. (2012). Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. [online] Annals of the New York Academy of Sciences, 1261(1), pp. 55–63. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22823394 [accessed 1 Nov. 2017].
Chronic stress causes the activation of the HPA axis, and of inflammtory cytokines which can lead to suppressed immunity Tian, R., Hou, G., Li, D. and Yuan, T.-F. (2014). A possible change process of inflammatory cytokines in the prolonged chronic stress and its ultimate implications for health. [online] The Scientific World Journal. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24995360 [accessed 1 Nov. 2017].
Autoimmune disease occurs when the body’s immune system attacks the body’s own cells and tissues. Therefore it involves an inflammatory response.
Autoimmune disease and severe infections are risk factors for schizophrenia and other mental illness Benros, M. E., Eaton, W. W., & Mortensen, P. B. (2014). The epidemiologic evidence linking autoimmune diseases and psychosis. Biological Psychiatry, 75 (4), pp. 300–6. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24199668 [accessed 1 Nov. 2017].
In some studies, a prior autoimmune disease increased the risk of depression by 45% Benros, M. E., Waltoft, B. L., Nordentoft, M., Krogh, J. and Mortensen, P. B. (2012). Autoimmunity and infections as risk factors for depression and other severe mental illnesses. [online] Neurology, Psychiatry and Brain Research, 18 (2), pp. 40–1. Available at: http://www.sciencedirect.com/science/article/pii/S0941950012000152 [accessed 1 Nov. 2017].
Brain-reactive antibodies (antibodies which only affect brain tissue) and inflammation are the key factors implicated in the link between autoimmunity and mental health problems.
Brain-reactive antibodies are present in about 2-3% of the population and normally cause no harm.
Elevated brain-reactive antibodies have been found in pregnant mothers and their children who later develop autism Benros, M. E., Waltoft, B. L., Nordentoft, M., Krogh, J. and Mortensen, P. B. (2012). Autoimmunity and infections as risk factors for depression and other severe mental illnesses. [online] Neurology, Psychiatry and Brain Research, 18 (2), pp. 40–1. Available at: http://www.sciencedirect.com/science/article/pii/S0941950012000152 [accessed 1 Nov. 2017].
In response to infection and/or inflammation, the release of inflammatory cytokines stops the development of new nerve cells in the brain known as “neurogenesis” or “neuroplasticity”.
Evidence indeed shows that infection and inflammation, which activate the release of cytokines, affect behaviour and cognitive functions such as memory.Miller, A. H., Maletic, V. and Raison, C. L. (2009). Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. [online] Biological Psychiatry, 65(9), pp. 732–741. Available at: http://www.biologicalpsychiatryjournal.com/article/S0006-3223(08)01532-1/fulltext [accessed 1 Nov. 2017].
Just as inflammation and inflammatory cytokines can reduce neurogenesis, inflammation is also implicated in neurodegenerative diseases such as Alzheimer’s disease.
The chemical markers associated with inflammation are consistently raised in Alzheimer’s and can be used to predict cognitive decline and the development of dementia.Najjar, S., Pearlman, D. M., Alper, K., Najjar, A. and Devinsky, O. (2013). Neuroinflammation and psychiatric illness. Journal of Neuroinflammation, 10 (1), p. 43. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23547920 [accessed 1 Nov. 2017].
During any physical illness, the immune system communicates with the brain through the secretion of cytokines.Yirmiya, R. (2000). Depression in medical illness: the role of the immune system. [online] The Western Journal of Medicine, 173 (5), pp. 333–6. Available at: https://www.ncbi.nlm.nih.gov/pubmed/11069873 [accessed 1 Nov. 2017].
Due to the interaction between the immune system and the brain, non-neurological infections such as pneumonia and urinary tract infection (UTI) can be accompanied by acute syndromes of brain dysfunction Han, J. H. and Wilber, S. T. (2013). Altered Mental Status in Older Emergency Department Patients. [online] Clinics in Geriatric Medicine, 29 (1), pp. 101–36. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614410/ [accessed 1 Nov. 2017] characterised by delirium and confusion. Inouye, S. K., Bogardus, S. T. Jr., Charpentier, P. A., Leo-Summers, L., Acampora, D., Holford, T. R. and Cooney, L. M. Jr. (1999). A multicomponent intervention to prevent delirium in hospitalized older patients. [online] The New England Journal of Medicine, 340 (9), pp. 669-76. Available at: https://www.ncbi.nlm.nih.gov/pubmed/10053175 [accessed 1 Nov. 2017].
Benros, M. E., Eaton, W. W., & Mortensen, P. B. (2014). The epidemiologic evidence linking autoimmune diseases and psychosis. Biological Psychiatry, 75 (4), pp. 300–6. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24199668 [accessed 1 Nov. 2017].
There is strong evidence associating infectious agents with mental health issues.
These infectious agents can cause mental health issues, including cognitive, psychotic and mood disorders.
Viruses and bacteria can act as endocrine disruptors, disturbing hormonal balance. They can also create an inflammatory-immune response.
Epstein barr Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 285.
A prior history of hospitalization with infection increased the risk of depression by 62% Benros, M. E., Eaton, W. W., & Mortensen, P. B. (2014). The epidemiologic evidence linking autoimmune diseases and psychosis. Biological Psychiatry, 75 (4), pp. 300–6. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24199668 [accessed 1 Nov. 2017].
HIV has been associated with a large number of psychiatric illnesses from depression to substance abuse.
Patients affected with sepsis (sepsis occurs when infectious agents (or toxins) enter the bloodstream and tissue and can cause serious organ damage and ultimately death if not treated) and encephalitis have been shown to have cognition issues long after the infection has cleared.
Candida albicans is a fungal infection.
All parasites emit toxins known as the indole catabolites. These burden the liver and kidneys and can make you become fatigued, irritable and can cause weight gain.
A study in 2006 showed that women with high levels of toxoplasma were more likely to give birth to children who later became schizophrenic and had birth defects Scott, T. and Gittleman, L. (May 2015). The Parasite/Anxiety Connection. [online] The Anxiety Summit, Season 3. Available at: http://season3.theanxietysummit.com/ [accessed 1 Nov. 2017].
An inflammatory response can be triggered by a number of factors. If these triggers continue over a period of time, inflammation can become chronic.
Sugars and refined carbohydrates Kharrazian, D. (2013). Why Isn’t My Brain Working? Carlsbad, CA: Elephant Press, p. 459.
Nutritional deficiencies Hyman, M. (2008). The UltraMind Solution. New York: Scribner, pp. 171-94.
Alcohol Kharrazian, D. (2013). Why Isn’t My Brain Working? Carlsbad, CA: Elephant Press, p. 459.
Often caused by food allergens such as gluten Kharrazian, D. (2013). Why Isn’t My Brain Working? Carlsbad, CA: Elephant Press, p. 459.
Food allergies can be a major cause of brain inflammation Hyman, M. (2008). The UltraMind Solution. New York: Scribner, pp. 171-94.
Fewer than seven hours a night.Hyman, M. (2008). The UltraMind Solution. New York: Scribner, p. 185.
Sedentary behaviour may contribute to negative mood by enhancing the inflammatory signaling pathway and increasing mood disturbance.Endrighi, R., Steptoe, A. and Hamer, M. (2015). The effect of experimentally induced sedentariness on mood and psychobiological responses to mental stress. The British Journal of Psychiatry. Available at: http://bjp.rcpsych.org/content/208/3/245 [accessed 1 Nov. 2017].
Excessive exercise or exercise which is too intense may lead to an excess release of stress hormones, physical damage, free radical damage and inflammation. This in turn may contribute to the development of mental health disorders.
Poor digestion Hyman, M. (2008). The UltraMind Solution. New York: Scribner, pp. 171-94.
Use of medicines such as antibiotics, NSAIDs (non-steroidal anti inflammatory drugs), proton pump inhibitors Minocha, A. (2014). Is It Leaky Gut or Leaky Gut Syndrome? Shreveport, LA: Logos Enterprises LLC.
Toxicity and then inflammation can also be triggered by certain pharmaceutical and recreational drugs such as alcohol, antibiotics, contraceptive pills, etc.
Trauma, whether physical or psychological, can lead to inflammation.
Chronic childhood trauma such as abuse will tend to cause mental health issues, not just for psychological reasons, but also for biochemical ones — the stress to the system involved in chronic trauma can lead to inflammation, which in turn can lead to mental health issues.

References: V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V.