There is growing evidence that inflammation – already known to be a cause of many whole-body diseases – is also involved in diseases of the brain, including psychiatric conditions like depression.
Depression is a common and crippling disease affecting over 350m people worldwide. Around 20% of the UK population will suffer from depression at some point in their lives, with symptoms varying from feelings of sadness and hopelessness through to suicidal thoughts. The disease may be a response to bereavement or other life events or emerge without any obvious cause. All too often it persists, sometimes for life.
Despite its high prevalence, the disease is poorly understood. It is often put down to a disturbance in brain chemistry and treated in a trial-and-error manner with talking therapies and drugs that are designed to re-balance brain chemistry. For many, these approaches eventually work, but all agree that better treatments are needed and these require a better understanding of the disease.
Beating two disorders with one pill
Inflammation is the body’s response to injury or infection. Cells and proteins are mobilised to deal with the injury, do their job and then are demobilised. However, inflammation, when not properly controlled, can cause damage and disease, such as rheumatoid arthritis. These types of diseases are often controlled with anti-inflammatory drugs.
Recently, it has been suggested that depression is also an inflammatory disease. The first evidence came from people with diseases like rheumatoid arthritis and psoriasis who were also severely depressed. When these people were treated with anti-inflammatories, both their arthritis and their depression improved, suggesting that inflammation in the body was affecting the brain to cause depression.
Of course, their depression may have improved because their other physical conditions had cleared up, but the evidence strengthened when it was shown that some people with depression, and no other disease, had increased levels of blood markers of inflammation. When their brains were looked at in the latest imaging machines, tell-tale signs of inflammation were present.
All of this evidence has led scientists to think of depression in a different way: as a disease of the whole person in which the symptoms are most evident in the brain, and where treatments targeting inflammation in the body might resolve the brain problems. However, it is likely that inflammation is not always the cause of depression, and we know that inflammation comes in different types that require different treatments. So, the current problem is how to identify which of the many patients with depression have inflammation as an underlying cause and exactly what type of inflammation they have. If we can develop simple blood tests to analyse inflammation in depressed patients we would be better placed to choose the best drugs to treat individual patients.
A group of UK scientists have teamed up with researchers from several pharmaceutical companies to investigate whether mood disorders, such as depression, and neurodegenerative diseases, such as Alzheimer’s disease, could be treated by targeting the immune system. The group is called NIMA (Neuroimmunology of Mood Disorders and Alzheimer’s Disease).
The first stage of NIMA’s work (currently ongoing) is to develop blood tests and brain imaging tests that can precisely identify those people who have depression associated with whole-body and brain inflammation. The final blood test will likely look at multiple markers of inflammation in the blood and give information that not only tells the clinician that the patient has inflammation but also what sort of inflammation it is. It will then be possible to select the best possible anti-inflammatory drug for that patient, improving the chance of a successful treatment.
And here’s where the clever part of NIMA comes in: to make a new drug costs a huge amount and takes years, but the partner pharmaceutical companies already have many anti-inflammatory drugs in their lockers which have been tested and shown to be safe in patients but are not yet available on the market. NIMA scientists will be able to select drugs from this resource, test them to confirm that they have the desired activity and then take them into small, fast clinical trials in highly selected patients with the right sort of disease.
The new approach of identifying the right patients to treat with the right drugs – called “stratified medicine” – is being used in many areas of medicine, but the work of NIMA means that one of its early successes might be in one of the most difficult diseases to treat: depression. While reaching for the ibuprofen will not resolve depression in everyone, there is the real prospect that many with depression associated with inflammation will soon benefit from individually tailored anti-inflammatory treatments.