Is Depression an Inflammatory Disease?
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 50% 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.
