How long-term depression alters the brain

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By Maria Cohut

Depression has become a common mental health problem. For some, this condition lingers for many years, and scientists now strive to understand how that might affect the brain, and how treatments should be adjusted to address these changes.

When depression doesn’t loosen its grip for a decade, how does it impact the brain?
According to data from the Centers for Disease Control and Prevention (CDC), across the United States, 8.1 percent of people over the age of 20 have depression over any given 2-week period.

For some people, depression might only be episodic and overcome within a matter of weeks or months.

However, for others diagnosed with major depression, the condition could persist for years, affecting their lifestyle and quality of life.

Looking at cases in which major depression lasts for over a decade, researchers from the Centre for Addiction and Mental Health (CAMH) in Ontario, Canada wanted to investigate whether living with this condition for so long would significantly impact the brain, and if so, how.

Dr. Jeff Meyer, from the CAMH, led a study focusing on that question. He and his team compared the brain scans of people who had lived with untreated depression for 10 years or longer with those of people with a shorter history of depression.

The findings — published last week in The Lancet Psychiatry — suggest that specialists might want to change their approach to treating long-term depression as it progresses to match its increasing neurological impact.

Depression may be progressive

Dr. Meyer and team worked with 80 people aged 18–75. Of these, 25 had lived with depression for longer than 10 years, 25 had had the condition for less than a decade, and 30 were depression-free. This final cohort made up the control group.

In a study from 2015, Dr. Meyer and his colleagues saw that during episodes of major depression, people’s brains would exhibit markers of inflammation.

Anhedonia, or loss of pleasure in usually enjoyable activities, is often associated with depression. What are the underlying mechanisms?
Based on that knowledge, in the new study, he wanted to explore whether the brain inflammation worsened over time in people with long-lasting depression.

The scientists determined the severity of the neuroinflammation using a type of brain scan known as positron emission tomography (PET). This allowed them to monitor the activity of microglia, a type of cell found in the central nervous system, which are associated with the inflammatory response to injury.

Active microglia produce translocator protein (TSPO), which is a key marker of inflammation.

Through the PET scans, Dr. Meyer and team found that the concentration of TSPO was 29–33 percent higher in the brains of people who had lived with depression for more than a decade.

These inflammation markers were seen in three brain regions in particular: the prefrontal cortex, the anterior cingulate cortex, and the insula.

Consistent with previous findings, the brains of those who had lived with untreated depression for shorter periods of time still had higher concentrations of TSPO than the brains of healthy controls.

More focused studies required

According to the researchers, these results suggest that long-term depression should be treated as a different stage of the same condition, as it may require a different therapeutic approach than depression in its earlier phases.

This, they add, is similar to the strategy applied in the case of neurodegenerative diseases, which are also characterized by heightened brain inflammation.

“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,” notes Dr. Meyer.

If depression, although not a neurodegenerative disease, is similar to such conditions — that is, characterized by an increasingly serious inflammatory response in the brain — then it may be adequate to treat it with anti-inflammatory drugs, Dr. Meyer suggests.

Therefore, he argues that further studies should look into the possibility of repurposing such medication as therapy for depression.

Another question that should be answered, he concludes, is what the best therapy for people with long-term major depression might be, since this specific population does not usually benefit from dedicated studies.

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