Depression alters the brain over the years and aggravates inflammation, suggesting the need to change how we think about depression as it progresses.
In an earlier study, Dr. Meyer's team discovered the first definitive evidence of inflammation in the brain in clinical depression.
This study provides the first biological evidence for large brain changes in long-lasting depression, suggesting that it is a different stage of illness that needs different therapeutics - the same perspective taken for early and later stages of Alzheimer's disease, he says.
Yet currently, says Dr. Meyer, regardless of how long a person has been ill, major depressive disorder is mainly treated with the same approach. Some people may have a couple of episodes of depression over a few years. Others may have persistent episodes over a decade with worsening symptoms, and increasing difficulty going to work or carrying out routine activities.
Treatment options for this later stage of illness, such as medications targeting inflammation, are being investigated by Dr. Meyer and others. This includes re-purposing current medications designed for inflammation in other illnesses to be used in major depressive disorder.
In the study, brain inflammation was measured using a type of brain imaging called positron emission tomography (PET). The brain's immune cells, known as microglia, are involved in the brain's normal inflammatory response to trauma or injury, but too much inflammation is associated with other degenerative illnesses as well as depression. When microglia are activated, they make more translocator protein (TSPO), a marker of inflammation that can be seen using PET imaging.
The study involved 25 people with more than 10 years of depression, 25 with less than 10 years of illness, and 30 people with no depression as a comparison group. TSPO levels were about 30 per cent higher in different brain regions among those with long-lasting untreated depression, compared to those with shorter periods of untreated depression. The group with long-term depression also had higher TSPO levels than those with no depression.
Dr. Meyer also notes that in treatment studies, patients with serious, longstanding depression tend to be excluded, so there is a lack of evidence of how to treat this stage of illness, which needs to be addressed.