Mental Health

The surprising link between depression and inflammation

Depression is a term used to describe a collection of symptoms that together significantly impair a person’s mood and day-to-day functioning. Research shows it’s the leading cause of disability across the world. It negatively impacts how depressed individuals show up to school and work and how much they can enjoy their relationships and everyday activities. We look at the causes of this common condition and explore a new theory that suggests inflammation may play a role.

What are the symptoms of depression?

The core symptoms of depression are persistent sadness or low mood. It also includes a marked loss of interest or pleasure in activities, even in activities we normally enjoy.
While many consider it a disease of the brain, it can affect the whole body. Other common symptoms include:

Disturbed sleep
Loss of libido
Changes in appetite or weight changes
Fatigue
Poor concentration
Feelings of worthlessness
Excessive guilt
Recurrent thoughts of death

A person with depression may also withdraw socially and experience difficulties in their close relationships.

Depression is diagnosed in cases where at least five of the above symptoms are present, these symptoms are impairing normal functioning, and have lasted for at least two weeks. Guidelines are also clear that depression can only be diagnosed in cases where symptoms are not due to a medication side-effect or drug or alcohol misuse.

Who’s most at risk?

Having an immediate family member with depression or another mood disorder can increase our risk. Longstanding illness, such as heart disease or cancer, can also significantly increase our risk. Women are also more likely to develop depression than men and this is particularly common after childbirth or during the menopause.

What causes depression?

The exact causes of depression are unknown. We often hear it described as a ‘chemical imbalance’ in the brain, which alludes to a longstanding theory that depression is caused by a deficiency of serotonin. Serotonin is the neurotransmitter (or brain chemical) we associate with good mood and feelings of wellbeing.

The ‘serotonin hypothesis’ of depression was developed over half a century ago when doctors treating tuberculosis patients accidentally discovered that certain antibiotics made their patients feel euphoric. Further investigation revealed the antibiotics in question were restricting the activity of an enzyme called monoamine oxidase (MAO). MAO degrades neurotransmitters (namely serotonin, dopamine and norepinephrine) associated with good mood, focus and wellbeing. Researchers concluded that low levels of these neurotransmitters (and particularly serotonin) were causing low mood and depression and, since then, this hypothesis has defined the treatment of the condition.

Typical treatment

Today, selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medication. After carrying a message from one nerve cell to another, serotonin is usually reabsorbed by the brain (a process known as reuptake). SSRIs work by blocking this reuptake so that more serotonin is available to pass further ‘good mood’ messages to nearby nerve cells, theoretically improving the symptoms of depression.

There are holes in the serotonin hypothesis though. SSRIs don’t work for everyone. Only approximately 50% of people prescribed with these drugs see an improvement in their depression. Further, researchers have not been able to explain why levels of serotonin become low in the first place. In other words, we have no idea why depression takes hold in the brains of some individuals and not in others.

A new theory

In recent years, researchers have noticed that many of the symptoms of depression are the same as our ‘sickness behaviours’. These are a cluster of behaviours that occur when we become ill with an infection. They have evolved to provide our body with the ideal conditions for rest and repair and to reduce the likelihood of infecting others (ensuring the survival of the species).

Bearing a striking similarity to many depressive symptoms, sickness behaviours include:

Social withdrawal
Loss of interest in day-to-day activities
Loss of appetite
Inactivity
Fatigue
Shivering
Mood changes
Cognitive impairment.

This observation has led researchers to further explore the links between depression and the immune system. Many now believe that wayward immune function and chronic inflammation may be fuelling depression and other mood-related disorders.

The inflamed brain

When our body is injured or invaded by a threatening pathogen, this threat is met by our white blood cells (or leukocytes). First to the scene are a variety known as mast cells. These cells are constantly searching for suspicious substances and when they find something, they pump out an inflammatory neurotransmitter known as histamine. This usually takes place within minutes to hours of a threat entering the body.

The inflammatory response that follows works to protect the body. Inflammation helps to dilate blood vessels ensuring back-up immune cells can quickly reach the scene. Inflammatory signals are then transported around the body by proteins known as cytokines, which mobilise other immune cells to come and join the fight. There is a dark side to this inflammation, however. If levels are not returned to normal after the threat has been neutralised, runaway inflammation can cause untold damage to healthy tissue.

How could this cause depression?

Researchers used to believe the brain was immune privileged. This means that it has its own immune defences entirely separate to the rest of the body. They believed that the brain was separated from the rest of the body by the blood brain barrier. This barrier prevented any immune cells or cytokines from getting in and causing damage.

We now know, however, that cytokines are perfectly capable of crossing the blood brain barrier. The inflammation theory of depression suggests that this leak of inflammatory proteins into the brain can lead to changes in how we think, feel and behave. This may go some way to explain why studies show those with inflammatory illnesses (such as arthritis or psoriasis) have a significantly increased risk of depression.

While it was previously thought that the pain and inconvenience associated with these conditions caused depression in patients, it may actually be the high levels of inflammatory proteins in their body that are to blame.

While research is in the early stages, there’s growing evidence to support this new theory. In a recent trial, 30 people were injected with a safe, disease-causing bacteria or placebo. The results showed that those who were injected with the bacteria had an elevated immune response and were subsequently more depressed than those who received the placebo. Crucially, the concentration of cytokines in their blood was an accurate predictor of the severity of the depression. The more inflammation, the more severe the depression.

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