The Link Between Depression and Inflammation
Research suggests that individuals with a diagnosis of clinical depression have a 30 % increase in inflammation; similarly increased inflammatory markers are also seen in a multitude of chronic conditions prevalent in the contemporary Western World.
This article explores emerging research that suggests the immune system – especially inflammation within the brain – is an important factor in the pathophysiology of depression.
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Depression
The Mental Health Website offers this 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
When the immune system is attacked by bacterial or viral infections, toxins or even a physical injury, this creates an inflammatory response. This response sends out messengers called cytokines which are either pro- or anti-inflammatory.
Cytokines
Cytokines are specific chemical messengers that are made by immune (and some other) cells and then released whenever an inflammatory process is triggered. As they are released into the blood, these cytokines affect the function of every single organ and tissue in the body, including the brain.
Research has shown that when an infection is present, “transient brain cytokine activation coordinates a large number of behavioral changes including weakness, listlessness, malaise, low appetite, fatigue and transient mood changes collectively referred to as ‘sickness behavior’.”
This ‘sickness behavior’ serves an important purpose and generally resolves within a few days after the person’s innate immune system is no longer active, though brain immune activation and/or systemic immune activation can lead to considerable, extended induction of brain cytokines.
Short-term, acute inflammation is a protective characteristic of the immune system, but long-term, chronic inflammation risks causing tissues to be destroyed and healed at the same time, ultimately causing a number of problems within the body over the long-term.
Chronic Inflammation, Cytokines and Depression
Microglia cells are the brain’s immune cells and these are the central nervous system’s first (and main) line of defense in the event of an infection. These cells comprise around 10-15% of the brain’s overall mass.
These cells help protect the spinal cord and brain from pathogens while clearing away any debris like beta amyloid plaques – a central feature within the pathology of Alzheimer’s disease.
When one microglia cell is activated, inflammation is created which can have a domino effect, thus causing other microglia cells to become active as well.
An array of human and animal studies has shown that cytokines are responsible for causing the symptoms and signs of disease. Research has suggested a demonstrable 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.”
In fact, an article on ScienceDaily cited research which highlighted the link between depression and cytokines. The article states, “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 capable of inducing the synthesis of various enzymes within activated immune cells. In particular, two of these which are abbreviated to IDO and GTP-CH1.
The IDO enzyme causes tryptophan to be broken down to kynurenine rather than serotonin. This causes levels of serotonin to be lower, often resulting in low mood.
Simultaneously, chronic inflammation also activates the GTP-CH1 enzyme which leads to the production of neopterin at the expense of tetrahydrobiopterin (BH4).
BH4 is essential in the synthesis of neurotransmitters including serotonin, but especially the neurotransmitter dopamine. Low dopamine levels are also linked to depression, with depression caused by low dopamine activity being different to that caused by low serotonin.
Where individuals have low levels of dopamine they are reported as struggling to motivate themselves, often feeling hopeless and worthless about their lives. However, where they are able to become motivated they are able to enjoy themselves.
This is different to low serotonin-based depression which is often linked to the loss of ability to enjoy things although, of course, it is possible to suffer both low serotonin and low dopamine at the same time.
Chronic, long-term stress has been shown to change immune cells’ gene activity before they enter the bloodstream, preparing them to fight an infection which does not exist. Because of this, unnecessary inflammation occurs which causes problems with bodily processes and tissues.
This chronic inflammation is commonly linked with disorders such as cancer, high cholesterol and heart disease. Brain inflammation however has been associated with a number of disorders including Parkinson’s disease, multiple sclerosis and Alzheimer’s disease.
Many people suffer from higher readings of inflammation in their bodies than is considered to be healthy. This is something that must be addressed, but it is considered to be largely caused by regular lifestyle choices within the Western World such as poor diet, ongoing stress and bad lifestyle choices.
Research is now inferring that as well as inflammation being linked to chronic conditions like diabetes and cancer, it may also have a significant impact on the onset of depression with many now considering depression to be a symptom of chronic inflammation.
Triggers of Inflammation
While physical injury or infection can trigger an immune response and as a result brain inflammation, this can also be caused by a range of other factors which include:
- A high carbohydrate diet
- Excess intake of omega-6 fatty acids / trans fats
- Lack of exercise
- Exposure to environmental toxins or chemicals
- Obesity, diabetes or asthma
- Stress and emotional trauma
- Head trauma
- Gluten
Anti-Inflammatory Diet
The majority of people within the Western World adopt a diet which provokes inflammation due to the presence of excess sugar, refined flour and inflammatory fats such as rancid, trans and some omega 6 fats. The same diet is also low in foods which reduce inflammation such as fermented foods, long-chain omega 3 fats and vegetables. As a result of this, several studies have linked the Western diet with depressive disorders.
Inflammation can be controlled however by making specific changes to diet and lifestyle, and research from 2014 has shown that providing patients with anti-inflammatory treatment can help reduce depressive symptoms.
A nutrient-dense, wholefood diet, plenty of sleep, managing stress and engaging in appropriate levels of physical activity can all contribute to an anti-inflammatory lifestyle and diet.
Conclusion
Inflammation is a major factor in depression, so being able to identify and remove possible causes such as food intolerances, heavy metals, gluten, toxins and chronic infections should be a key factor in alleviating depressive symptoms when done in conjunction with an anti-inflammatory diet and lifestyle choices.
References are available on request.
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Last updated: Sep 3, 2018 at 8:58 AM
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