Friday, August 24, 2012

Is Depression, Caused by Inflammation?

Depression is a leading cause of disability and is the fourth largest cause of burden of disease amongst all diseases (1) and affects one in three women.  Anybody who has ever suffered from depression or has a loved one who suffers from it knows how debilitating it can be. 

Treatment has traditionally focused on improving serotonin levels, but figures show around 35% remission after initial treatment and approximately 70% remission after four cumulative treatments (1) It is necessary to look beyond serotonin to find out what is causing depression, and adapt natural support to rebalance the underlying causes.


Raised inflammatory markers in depression

People with depression have increased levels of inflammatory substances such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-α (TNF) or C-Reactive Protein (CPR) in the blood(1,2,6,8) Higher levels of these markers affect brain signalling and produce symptoms such as fatigue, changes in appetite, increased sleep, lack of motivation, negative mood, decreased cognition and weight changes (5,8) – the classical symptoms of depression.

Conversely, people who are treated with inflammatory substances (eg interferon in cancer treatment or chronic infections) start to show depression-like symptoms (2) So what is the link between inflammation and depression?


Inflammation depletes serotonin

Inflammatory substances such as IL1, IL-6, TNF and CRP stimulate the formation of IDO (indoleamine 2,3-dioxygenase), an enzyme involved in the tryptophan metabolism. Unfortunately, this enzyme does not push tryptophan towards the serotonin pathway, but towards the kynurenine pathway instead. (1,3) This can reduce serotonin levels by 25-50%. (1) It stands to reason that we need to reduce inflammation to help improve depression, but to effectively do this we need to find out where this inflammation is coming from in the first place.


Where does inflammation start?

Conditions such as endometriosis, PCOS and other reproductive disorders are linked with inflammation, and very often patients suffering from any of these conditions also suffer from low moods or depression. The debilitating symptoms are enough to make anyone feel low, but the underlying inflammation is the real trigger that needs to be looked at.

Research shows that inflammation also often starts in the digestive tract, with harmful bacteria causing leaky gut (7). As the intestinal wall becomes more permeable, the immune system is activated. As part of the immune response there is an increased production of pro-inflammatory hormones such as IL-1, IL-6, TNF and interferon-ϒ (IFN). As described above, these substances increase the metabolism of tryptophan to the neurotoxic quinolinic acid rather than the ‘feel good’ hormone serotonin (3).  These hormones can also trigger an auto immune response triggering conditions like Rheumatoid arthritis, hashimotto's, Lupus and possibly MS.

Not everybody who suffers from frequent low moods or is depressed will have PCOS, endometriosis, or bowel dysbiosis; but everybody would benefit from finding out what underlying causes trigger low moods or depression, especially if they have tried anti-depressants and find they don’t work.


What can you do about this yourself?

A holistic treatment plan that addresses the cause and not just the symptom is crucial.   Look beyond the boundries of a general 'symptom based' simplistic consultation.   Fourteen years of clinical experience highlights the need for segmentation based, multilayer, diagnosis techniques as part of the initial step in getting to the cause. 

Establishing the underlying cause, ensures effective natural support.  Targeting medicinal herbs and orthomolecular nutrients assist in reversing the cause. 

There is a great deal of research to promote the benefits of incorporating natural support in depression.  Even something as simple as EFA's such as Omega3 Fatty acids have been found to make a difference.  Omega 3 poly unsaturated fatty acids found in fish oil not only have a strong anti-inflammatory effect, but also improve fluidity of the cell membranes (3,9). There are many studies that associate increased intake of omega 3 EFA’s with improved cognition and moods. (9) Apart from this, they can improve serotonin binding (10), further improving moods.

EFA’s could be part of a holistic treatment plan, but as each patient is different and some may already be on anti-depressants, each treatment approach is different, too. It is always best to contact your health care practitioner to provide a solid platform to redefine your health.

Narelle Stegehuis, is a practicing medical herbalist and naturopath specializing in restorative endocrinology for women, with over 14 years clinical experience.  She is both an accomplished writer, editor and technical training advisor.  A recipient of the Australian Naturopathic Excellence Award, Narelle adopts an integrated approach of both medical science and traditional complementary health care principles.  She can be contacted at

1. DM Christmas, JP Potokar, SJC Davies, “A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase – Neuropsychiatric disease and treatment 2011:7 431-439
2. B Messay, A Lim, AL Marshland, “Current understanding of the bi-directional relationship of major depression with inflammation” – Biology of Mood & Anxiety Disorders, 2012, 2:4
3. M Maes, “The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression” – Neuroendocrinology letters 2008:29(3):1-000
4. Chrousos GP et all, “ Interactive functional specificity of stress and immune response: the yin, the yang, and defence against two major classes of bacteria” – Journal of Infectious Disease, 15th Aug 2005;192(4):551-555
5. R Dantzer et all, “From inflammation to sickness and depression: when the immune system subjugates the brain” – Nature Reviews Neuroscienice 9, January 2009, 46-56, doi:10.1038/nrn2297
6. R Dantzer, “Depression and inflammation, and intricate relationship” – Biological Psychiatry, vol 71, issue 1, p 4-5, 1st January 2012-07-01
7. Maes M et all, “Increased IgA and IgM response against gut commensals in chronic depression” – Journal of Affective Disorders, 11th March 2012, doi:10.101/
8. Krishnadas R, Cavanagh J, “Depression: an inflammatory illness?” – Journal of Neurology, Neurosurgery and Psychiatry, 83 (5) 495-502, doi:10.1126/jnnp-2011-301779
9. Nurk E, Devron CA, Refsum H et all, “Cognitive performance among the elderly and dietary fish intake: the Horland Health Study” – Am Journal of Clinical Nutrition 2007; 86:1470-1478
10. Huang JTJ, Leweke FM, Oxley D et all, “Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis” – Plos med 2006,3(11):e428