Depression changes the brain over time

Research from CAMH calls for different approach in therapeutic treatment

Depression changes the brain over time

A recent study by researchers at the Centre for Addiction and Mental Health (CAMH) showed that the brain changes with the progression of depression, suggesting that depression needs to be treated differently at every stage of the illness.

The team, led by Dr. Jeffrey Meyer, showed that people with longer periods of untreated depression — defined as lasting more than a decade — had significantly more brain inflammation compared to those who had less than 10 years of untreated depression.

This study is the first in its field to show biological evidence for how the brain changes in persistent depression. Consequently, it reveals that depression is not a static condition but is instead a degenerative brain disease like Parkinson’s or Alzheimer’s.

They examined how the total distribution volume of translocator protein (TSPO), which is a marker of microglial activation, correlated with the duration of untreated major depressive disorder, total illness duration, and antidepressant exposure.

It was important to study microglial activation, because microglia are involved in the brain’s normal inflammatory responses to trauma or injuries. However, too much inflammation has been associated with degenerative illnesses as well as depression.

Participants from the age of 18–75 were recruited for the study. They were from the Toronto area and CAMH, and they either had major depressive episodes or were healthy. This research was supported by the Canadian Institutes of Health Research, the Brain and Behavior Research Foundation, and the Neuroscience Catalyst Fund.

Using the Positron Emission Tomography, the researchers scanned three primary grey matter regions of interest and 12 additional regions to measure the total distribution volume of TSPO. The researchers also investigated the duration of untreated major depressive disorder, and the combination of total duration of disease and duration of antidepressant treatment.

The research found that the 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.

“An implication of our study is that the current approach for antidepressant treatment isn’t addressing the issue that the illness is changing over time,” said Meyer.

Currently, no matter how long a person has had depression, they are treated with the same approach at every level. Meyer advocates that treatment methods should address the illness differently as it progresses.

However, there is still a lack of evidence in how to treat depression in its later phases. “People can certainly respond to treatment after not responding to previous treatments, but the rate is lower so clinical trials often exclude people who have not responded to a few previous treatments,” said Meyer.

“We are testing whether current treatments for other illnesses could be applied in depression to influence inflammation to make it more curative. There are also new treatments being developed by companies for depression for the same intent,” said Meyer.

Meyer noted that one study is not enough to change the treatment, but he is hopeful that their work will have this impact soon.

Science in brief

A round-up of the top science stories from around the university

Science in brief

Dangerous driving

What may seem obvious to any good driver can now be backed up by statistics: dangerous drivers are more likely to hit children on their way to school.

Researchers from York University, the University of Toronto, and The Hospital for Sick Children camped out in front of schools during their morning drop-off hours, measuring pedestrian traffic and scanning the road for hazardous driving habits. Their observations were compared with 12 years of police data on pedestrian-motor vehicle collisions (PMVCs) near Toronto elementary schools. The study revealed that collisions involving children happen more often near schools with dangerous driving trends.

The most common offense? Of the 118 schools studied, 88 per cent displayed instances of unsafe parking and improper drop-offs, such as children being released from the wrong side of the street. Trends were higher in schools near high-speed roadways. Researchers urge the city to employ new strategies to alleviate traffic around school zones.

— Alastair McNamara


Study shows depression affects alertness more than lack of sleep

A new study lead by Azmeh Shahid of the Sleep Research Laboratory in U of T’s Department of Psychiatry is the first of its kind to connect depressive symptoms with impaired alertness.   

The researchers used the Toronto Hospital Alertness Tests (THAT), a scale asssessing alertness, to evaluate 60 healthy adults against 264 diagnosed patients. The participants’ average score (on a scale of zero to 50) was around 35 for the control group. A score below 20.5 is the cut-off point for THAT and it indicates “clinically significant” decreases in levels of alterness.   

This cut-off was used to define the patients as either having “normal” or “impaired” alertness. The results showed that daytime sleepiness is not the same as poor alertness, and that depressive symptoms like fatigue had a stronger effect on alertness levels than tiredness. 

Dr. Shahid said the results of the study “did not surprise” the research team, as other clinical patients have been observed to experience daytime sleepiness and alertness at the same time. 

Dr. Shahid explained the results of the study are “very exciting” because THAT can be used to differentiate alertness from sleepiness, which can aid in future studies. The first quantitative definition of “normal levels of alertness” was proposed by the study, but more research is still needed to solidify this definition. 

“I think this will have huge impact in clinical practice,” Dr. Shahid added.

— Sophia Savva 

Don’t Worry, Be Happy

With the loonie sinking and the world economy sputtering, it is hard not to worry about world issues. A new study warns against worrying too much, lest our brains turn to mush. 

Dr. Linda Mah of the University of Toronto and her colleagues examined recent studies of stress and anxiety in animal models and healthy individuals. Surprisingly, they found that chronic stress and anxiety can cause long-lasting damage in the brain.

Stress is a normal part of life, but if anxiety becomes chronic, it can lead to the degeneration and impairment of the brain’s hippocampus and prefrontal cortex. The former is known to play an important role in memory and the regulation of emotions, while the latter has been associated with personality distinction.   

The stress-induced damage to these parts of the brain leads to increased risk for depression and even dementia. 

The study concludes on a hopeful note by suggesting that stress-induced damage is “not completely irreversible.” Antidepressant treatment and physical activity may reverse brain damage, as these treatments have been found to increase the rate of hippocampal recovery. Either way, don’t worry about your worrying.

— Hariyanto Darmawan