Research is now frequently suggesting that people who have been diagnosed with clinical depression have a 30% increase in inflammation, a physical marker of many of the chronic conditions that are prevalent throughout the Western World today.
In this week’s article we look at the emerging research suggesting that the immune system and, in particular, inflammation in the brain — is an important contributor to the pathophysiology of depression.
Depression
The Mental Health Website give the following definition of Depression:
“Depression is a common mental disorder that causes people to experience depressed mood, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, low energy, and poor concentration.
Depression is different from feeling down or sad. Unhappiness is something which everyone feels at one time or another, usually due to a particular cause. A person experiencing depression will experience intense emotions of anxiety, hopelessness, negativity and helplessness, and the feelings stay with them instead of going away.”
Inflammation
Whenever the immune system is attacked by infections (viruses or bacteria), toxins, or even physical injury (such as a knee injury), it creates an inflammatory response — sending out messengers known as cytokines, which are either pro-inflammatory or anti-inflammatory.
Cytokines
Cytokines are chemical messengers (ie similar to hormones) made by immune cells (and certain other cells) and are released in every single inflammatory process. When they are released into the blood, cytokines can affect the function of every tissue and organ in the body, including the brain.
Research indicates that during an infection, “transient brain cytokine activation coordinates a large number of behavioural changes including weakness, listlessness, malaise, low appetite, fatigue and transient mood changes collectively referred to as ‘sickness behaviour’.”
This so-called sickness behaviour has a useful purpose and usually resolves within a few days once the innate immune system is no longer activated. However, systemic immune activation and / or brain immune activation leads to significant and prolonged induction of brain cytokines.
So while acute or short-term inflammation is a protective feature of the immune system, chronic or long-term inflammation, can cause simultaneous destruction and healing of the tissues, ultimately wreaking havoc on your body long-term.
Chronic Inflammation, Cytokines and Depression
Microglia cells, the brain’s immune cells, make up 15% of the brain’s overall mass and are your central nervous system’s first and main line of defence.
They protect the brain and the spinal cord from pathogens and clear away debris such as beta amyloid plaques; a prominent feature in the pathology of Alzheimer’s disease.
Once one of these cells is activated, it creates inflammation and can have a domino effect, causing other microglia cells to become active.
Extensive animal and human studies have clearly demonstrated that cytokines cause the symptoms and signs of disease and research suggests that there is also a clear biological link between the release of cytokines and depressive symptoms:
“First, in addition to producing all the symptoms and signs of physical illness, cytokines can provoke most, if not all, the symptoms of mental diseases, especially depression and schizophrenia.
Second, in addition to producing the mental symptoms of depression and schizophrenia, cytokines produce the physical signs commonly associated with depression or schizophrenia, such as, inflammation, hormone abnormalities, headache, and biochemical abnormalities.
Third, cytokines can pass from the blood to the brain. Also, they can be made by immune cells residing in the brain and there are receptors for cytokines throughout the brain.
Fourth, cytokines have powerful effects on neurotransmitter activities, including those linked with depression and schizophrenia, such as norepinephrine, serotonin and dopamine.”
A recent article on ScienceDaily cited research highlighting the link between Cytokines and depression, stating that “among patients suffering from clinical depression, concentrations of two inflammatory markers, CRP and IL-6, were elevated by up to 50 percent.”
Mechanisms by which cytokines are thought to cause depression
Cytokines are able to induce the synthesis of different enzymes in activated immune cells – two in particular which are abbreviated to IDO and GTP-CH1.
The IDO enzyme results in tryptophan (the precursor to the brain neurotransmitter serotonin) being broken down to kynurenine instead of being converted to serotonin, resulting in lower levels of serotonin (the happy brain chemical).
At the same time chronic inflammation also activates another enzyme called GTP-CH1 leading to the production of a product called neopterin at the expense of tetrahydrobiopterin (BH4).
BH4 plays a fundamental role in neurotransmitter synthesis including serotonin but particularly another neurotransmitter – dopamine. Low levels of dopamine are also relevant in depression. The depression caused by poor dopamine activity is different to that caused by low serotonin.
People with low dopamine are reported as having a hard time getting motivated, they feel worthless and hopeless about their lives but if they can get motivated they enjoy themselves (whereas low serotonin is associated with a loss of ability to enjoy activities). Of course people can suffer from both low dopamine and low serotonin.
Long-term or chronic stress has actually been shown to change the gene activity of immune cells before they enter the bloodstream, priming them to fight infection when there is no infection. As a result, inflammation occurs unnecessarily but still wreaks havoc on tissues and body processes.
Chronic inflammation is often associated with cancer and other disorders such as heart disease and high cholesterol. Brain inflammation, meanwhile, has been linked to several disorders, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.
The biggest problem in the Western World of today is that by virtue of several factors, including poor diet and lifestyle, most of us have higher readings of inflammation in our bodies than is considered to be healthy. This is something that clearly needs to be addressed.
Now research is suggesting that on top of inflammation being linked to chronic conditions such as cancer and diabetes, it could also play a major role in the onset of depression. Indeed, many now consider depression to be a symptom of chronic inflammation.
Triggers of inflammation
It’s not only physical injury or infections that can trigger an immune response and brain inflammation, many other factors can as well, for example:
- High carbohydrate diet
- Lack of exercise
- Stress and emotional trauma
- Head trauma
- Gluten
- Exposure to environmental toxins/chemicals
- Obesity, diabetes, asthma
- Diet
Anti-inflammatory diet
There are numerous problems with the modern diet that the majority of people living in the Western world adopt; It is high in foods that provoke inflammation, such as refined flour, excess sugar, inflammatory fats (eg rancid, trans and certain omega-6 fats). It is also very low in foods that reduce inflammation, such as vegetables , long-chain omega-3 fats and fermented foods. Numerous studies have associated the Western diet with major depressive disorder.
Inflammation is however something that can be controlled by making certain changes to your diet and lifestyle. Indeed, research from 2014 has found that providing patients with anti-inflammatory treatment can reduce depressive symptoms.
Adopting an anti-inflammatory diet and lifestyle means eating a nutrient-dense, whole foods diet, getting enough sleep, managing stress and engaging in appropriate (not too little or too much) physical activity.
We have written several blogs on the topic of the anti-inflammatory Paleo diet. You can find links to these at the bottom of this article.
Conclusion
Clearly inflammation is a significant factor in depression. So identifying possible causes, such as chronic infections, food intolerances, heavy metals, toxins and gluten, and removing them should be a key focus along with anti-inflammatory diet and lifestyle measures.
If you have any questions regarding the health topics that have been raised please don’t hesitate to get in touch with me via phone (01684 310099) or e-mail (amanda@cytoplan.co.uk).
Amanda Williams and the Cytoplan Editorial Team: Clare Daley, Joseph Forsyth and Simon Holdcroft
Related blogs
The Authentic Paleo Lifestyle – Part 2 – A Suitable Diet
The benefits of a ‘low-carb’ diet such as the ‘Paleo Diet’?
Last updated on 20th August 2019 by cytoffice
An excellent article. A lot to take in, but well worth reading – and saving for future reference.
A thoughtful informative article. Thanks.
Fascinating. What supplements would you recommend to support the system and what effect do chemical anti-inflammatories have in this picture?
Hi Joanne,
Many thanks for your question. With regards to appropriate supplements, it does very much depend on the person, but here are a few:
– Curcumin – you may be interested in our previous blog on CurcuminCurcumin
– Krill oil – this contains essential fatty acids, similar to fish oil, but also has astaxanthin an antioxidant. Fish oils could also be considered.
– Vitamin D – low vitamin D levels are linked to inflammation and have also been linked to depression
– Plant antioxidants / phytonutrients eg flavonoids and carotenoids
– Live bacteria supplements
– A multivitamin / mineral with good levels of B vitamins which are important for neurotransmitter synthesis
With regards to chemical anti-inflammatories, there is very much mixed data on these. If you would like to get in touch (clare@cytoplan.co.uk) I would be more than happy to discuss this with you.
All the best,
Clare
Really excellent article thank you! Here’s another paper on the subject http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392963/ ‘Cytokines Sing the Blues’ what a great title 🙂
Are there any supplements one can take as protection against the inflammation mentioned in the above article?
Hi Catherine,
Yes there are supplements that can be taken to protect against inflammation but it is important that these are combined with an anti inflammatory diet. It is best to look at these things on an individual basis so if you would like help on this please do e-mail me at amanda@cytoplan.co.uk,
All the best,
Amanda
This all makes sense to me. I have had a stage four tonsil cancer and neck. I had to have 25 sessions of radiotherapy and 6 of Chemotherapy . At the time I was going through immense stress and believe , that was the cause of my cancer. It makes sense the body and mind are connected. Blood flows round our body, it doesn’t stop when it gets the head or visa versa. This all makes complete sense.
Thank you for the great article!
Great article. What research shows that a whole food high carb diet produces inflammation? thanks
Hi Nua,
The blog cites a high carbohydrate diet as being pro inflammatory, mainly because this type of diet is usually based on processed carbohydrates, that are high in sugar. You refer to “ A wholefood high carbohydrate diet” which could be slightly different in that it could be made from complex carbohydrates from vegetables, but also usually also includes wholegrains which can be inflammatory in some people. So to answer your question I really need to look at the exact make-up of the diet you are describing and for me to comment explicitly on the foods included. If you want to email me directly on this I am happy to revert with comments (amanda@cytoplan.co.uk)
All the best,
Amanda
Ok, it seems the article text is a bit misleading then:
“Triggers of inflammation…High carbohydrate diet” – maybe qualify this.
Obviously if someone has an intolerance that would cause inflammation but saying ” high refined carbohydrate” (or similar) diet would less confusing and more helpful. Otherwise please supply research (would be great to read), as it takes from an otherwise very interesting article.
Dear Amanda
Could this approach be appropriate for teenage depression? Or is there something else you would look at in that case?
best wishes
Kate
Dear Kate
Certainly inflammation could be playing a role in depression at any age and teenagers often eat diets high in sugar, inflammatory fats and low in vegetables ie an inflammatory diet. They may not be getting enough sleep and experiencing exam and social stresses. So there are plenty of factors that could contribute to inflammation and depression. Awful to think of anyone suffering this condition, but particularly at this sensitive time in their life.
I would always recommend that the person visit the GP for assessment and advice.
We do offer a free health questionnaire service and if the person would like to complete a health questionnaire we can send some written diet and supplement advice.
https://www.cytoplan.co.uk/nutrition-advice/educational-literature/health-questionnaire
Best wishes
Clare
Thank you, a very interesting article. I have interstitial cystitis together with GERD so am having to be extremely careful with my diet. I have cut out multivitamins too but wonder if you could suggest a supplement that would be beneficial.
Kind regards
Hello Loraine,
Thank you for your question. It would be useful to understand the cause for the GERD – for example whether it is due to a hiatus hernia?
In the meantime, with regard to supplements, I would recommend the following:
Slippery Elm – this contains mucilage a substance that becomes a slick gel when mixed with water. It coats the mouth, throat and intestines. People use it for GERD. You could empty the capsule and mix in a cold water to form a past and then slowly add some boiling water, stirring briskly. Take with food. Again this is used for GERD
Aloe Vera Inner Leaf gel – take 1 ml per kg body weight per day with food
A live bacteria supplement – Acidophilus Plus. There is much research of using live bacteria supplements in relation to many conditions including GERD. Take 1 per day on an empty stomach.
Additional supplements to consider:
Bromelain with meals to support digestion – poor stomach digestion can contribute to reflux. Low stomach acid can be a factor but bromelain is a more gentle approach than taking digestive enzymes with hydrochloric acid. Take 1 with each meal.
Phytoshield – high in antioxidants – flavonoids and carotenoids which are found in fruit and vegetables and eating lots of vegetables is anti-inflammatory. I am suggesting this for the interstitial cystitis. Take 1 per day with food.
I know you asked for 1 supplement and I have suggested 5 – initially it can be useful to take a variety of supplements and then reduce once you have symptoms better controlled.
In terms of diet you mention you are already being careful so you will know to avoid caffeine, chocolate, alcohol, spicy foods, sugary foods. Tomatoes and citrus may also need to be avoided. Sometimes it can be useful to cut out gluten grains and reduce other grains, in particular while trying to get the inflammation under control. Focus on eating plenty of vegetables which are anti-inflammatory. Healthy fats such as avocado, olive oil, coconut oil (in small quantities). Choose easily digested proteins such as white fish. Avoid heavy meals and red meat. Bone broths made with organic bones (eg chicken bones) can be very soothing for the gut.
We do offer a free health questionnaire service. If you complete the health questionnaire which you can find on our website at this link, we will send you some written diet and supplement suggestions. I hope this helps.
All the best,
Clare