Studying brain aging and working memory in individuals with major depressive disorder
Research
By
Melody Kwong
It is widely known that aging is associated with gradual physiological changes in brain and behaviour, however, there exists a knowledge gap in understanding how major depressive disorder (MDD) impacts brain aging and cognitive function.
Natalie C.W. Ho, MSc. Student at the Institute of Medical Science, University of Toronto, currently supervised by Dr. Benoit Mulsant, was the lead author on this study, with Dr. Sidney Kennedy and Dr. Katharine Dunlop as senior authors. In this study, her team examined the impact of brain aging—measured by brain chart-based centile scores—in major depressive disorder using a multi-site sample of individuals (12-65 years old). Analyzing the brain centile scores in individuals with MDD relative to non-depressed controls, the team found indicators that MDD patients may exhibit accelerated biological indices of aging. Continued research on the relationship between aging and pathophysiology will further improve the development of novel therapeutic strategies, and help to optimize existing treatments.
We spoke to Dr. Katharine Dunlop, one of the senior authors on this research paper, to learn more about their team’s findings.
Dr. Katharine Dunlop
How is brain aging measured and why is it important to study this in people with major depression? KD: Brain aging is measured using previously published growth charts from a large (>100,000) dataset across the lifespan. Like growth charts for height and weight, we characterized brain structure from MRI scans as a percentile, where a higher percentile means your brain is larger than others at the same age. People diagnosed with major depression may show a faster decline in cognition and change in brain structure, similar to the effects of aging. It is important to study the impact of brain aging in this population because it may have implications in response to antidepressant treatment.
What motivated this research?
KD: Previous studies investigating brain aging in depression found mixed results; some studies reported a significant difference in how the brain aged in depression and others didn’t. The brain growth chart tool—called BrainChart—is a relatively new tool to measure brain development and aging using the largest brain imaging sample available. We wanted to better understand the relationship between brain aging and depression using this new tool to help resolve some of this conflicting evidence.
What was the most important finding of this study, in your opinion? KD: Confirming previous work, we were able to show that people with depression had atypical patterns of brain aging related to people without depression. Furthermore, brain aging in people without depression was associated with working memory, or the ability to keep many things in mind at the same time. This same relationship was not seen in people with depression, indicating that the diagnosis could alter age-related changes in cognition.
Natalie C.W. Ho, MSc. student and lead author
How does this change treatment in the future?
KD: Although in its early days, better understanding the relationship between aging and mental illness could yield new or personalized treatment. Since the presence of a mental illness increases the likelihood of cognitive impairment later in life, these findings could help guide early intervention strategies aimed at preventing this later life decline.
Any next steps?
KD: The symptoms of depression differ a lot from one person to the next. We plan on characterizing subtypes of depression and how they relate to brain aging. This could be used to better tailor treatments or preventative strategies.
What is the major take home message for the public?
KD: Our study allows us to better understand how depression affects cognition, brain aging and development. Using MRI scans, we were able to show differences in brain aging its relationship to cognition in people with depression, which could help us tailor treatments or develop new ones.
Dr. Dunlop and team would like to thank the Ontario Brain Institute, CIHR, St. Michael's Foundation, CAN-BIND, and Lifespan Brain Chart Consortium for making this research study possible.