AGEING AND THE BRAIN
Depression linked to premature brain ageing
Evidence is accumulating that depression and premature brain ageing are closely linked
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t’s not unusual to feel older than your years, but that might be more true for some people than they realise. There’s growing evidence that mental illnesses such as depression are somehow related to a sufferer’s brain resembling that of an aged person. But does depression cause a brain to age prematurely or does premature ageing precede the onset of disease? Researchers use physical, cellular, and molecular markers to predict an individual’s ‘biological age.’ With these tools, they are trying to understand why biological age differs from actual age in some people. Research into accelerated brain ageing is an offshoot of this line of investigation. An individual’s chronological age can be predicted by the metrics of their brain. As humans age past 30, their brain starts slowly deteriorating over the remainder of their life. These changes are both physical, such as grey matter atrophy, and functional, such as a decline in cognitive flexibility, memory, and visual processing speed. However, some things, such as vocabulary and some verbal skills, survive the ageing process. With accelerated brain ageing, a person’s brain metrics belie their actual age. The changes may be slight, but a person’s brain looks and behaves closer to that of an older brain. Some researchers, such as Katharine Dunlop of Weill Cornell Medicine, are working to delineate the relationship between accelerated brain ageing
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and depression. In 2021, together with a team of researchers in the US and Canada, she published a paper on the subject in the journal Neuropsychopharmacology. They used images of more than 700 healthy adult brains to create a model that predicted age. When the model was used to predict the age of depressed patients, it predicted an age that was, on average, two years older than the patients’ actual age. Dunlop and her team also found that patients with older-looking brains were more likely to be impulsive, and males with older brains tended to have more severe symptoms. “We found that if you were more impulsive regarding financial decision-making, you tended to have an older-looking brain,” says Dunlop. This finding echoes a much larger study from the ENIGMA major depressive disorder consortium. In this large, multinational study, led by Laura Han from Amsterdam UMC, the Netherlands, the ENIGMA consortium found structural variation in depressed patients’ brains that made them appear to be approximately one year older. Dunlop says that prior to the ENIGMA MDD working group study, a few smaller studies showed “conflicting but not incompatible results” regarding whether brain ageing and depression were linked. Dunlop also remarks that although some conditions, such as schizophrenia and dementia, show “clear-cut” accelerated ageing,
things are a “little fuzzier” when it comes to depression. The ENIGMA study goes some way to settling the debate, however, as the largest study to date on the topic. In an effort to boost the study of accelerated brain ageing and depression, Han and her team also produced a web-based tool that allows other research groups to test their own data. “There are 77 structural brain features like thickness and surface area and volumes of the brain,” says Han. If another research team acquires these metrics and plugs them into the consortia’s web tool, it will offer up a prediction of brain age. Dunlop says she believes that brain ageing research is a stellar example of collaborative research done right. “The spirit of collaboration is exemplified in a lot of the brain ageing work because it requires a lot of data from multiple sources. That ENIGMA paper is a really good example of that,” she says.
