Depression changes the brain over time.

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Over years, depression quite literally changes the brain, new research shows. Importantly the researchers found that persistent depression may need a different therapeutic approach from all those that have been tried so far. They findings also raised the question: Is clinical depression always the same illness, or does it change over time?

What the researchers say: New brain imaging research shows that the brain alters after years of persistent depression, suggesting the need to change how we think about depression as it progresses.

The study, was published in The Lancet Psychiatry.

The research shows that people with longer periods of untreated depression, lasting more than a decade, had significantly more brain inflammation compared to those who had less than 10 years of untreated depression. In an earlier study the 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, the lead author says.

“Greater inflammation in the brain is a common response with degenerative brain diseases as they progress, such as with Alzheimer’s disease and Parkinson´s disease,” he says. While depression is not considered a degenerative brain disease, the change in inflammation shows that, for those in whom depression persists, it may be progressive and not a static condition.

Yet currently 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, including 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 (see recent TRs). 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 degenerative illnesses as well as depression.

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. Inflammation 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 inflammation levels than those with no depression.

The researchers also note 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.

So what? Treating depression with anti-inflammatory drugs is not a new idea. Nor is the idea that depression can increase in severity with age. What is new in this study is the idea that the two are linked and that depression becomes something very different involving changes in the way the brain functions over time. This will hopefully lead to the discovery of new and better treatments for people with long-standing depression—which is actually most depression sufferers of major depressive disorder over the age of 40.