For more than a decade, depression has been linked to a shrunken hippocampus, the main memory centre of our brain. But now, a study of more than 23,000 brain scans suggests this doesn’t stack up.
In 2015, a of nearly 9000 people – the largest of its kind at the time – concluded that people with recurrent depression have smaller hippocampi. It also suggested that growing number of depression episodes, implying that the mental health condition may be responsible for this shrinkage, rather than a small hippocampus causing depression.
Now, at Washington University School of Medicine in St Louis, Missouri, and her colleagues have analysed brain scans from 23,417 participants in the US and the UK across six large-scale datasets, including the UK Biobank. The team used modern imaging techniques that weren’t available in 2015, says Bijsterbosch.
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The researchers were surprised to find no significant link between depression – assessed via questionnaires – and hippocampal volume. “It is surprising [that] no [hippocampal] shrinkage was seen,” says at Southern Colorado TMS Center. “This study is very important and tells us we still need to learn more about all brain regions and not take hippocampal shrinkage as a given.”
The team did link depression to reduced grey matter volume or cortical surface area in the frontal cortex, the anterior cingulate and the insula. All three of these areas are involved in emotional regulation. The frontal cortex is also involved in judgement and self-control, while the anterior cingulate has been linked to decision-making and motivation, and the insula helps perceive pain.
“All of these [traits and conditions] are disrupted in depressive symptoms,” says Fleming. The reduced volumes may therefore help explain common depression symptoms, such as brain fog and pain, he says.
It is unclear why depression seems to affect these areas specifically. One possibility may be that areas like the insula have a high degree of neuroplasticity, which may make them more vulnerable to the stress of depression, says Bijsterbosch.
Bijsterbosch stresses that her team measured depression at only a single time point, while the 2015 researchers tracked the condition across multiple episodes. What’s more, most of the participants in the latest study had mild to moderate symptoms, so hippocampal shrinkage may occur in recurrent or severe cases, she says.
If the effects of depression on the brain are explored further, this could help us understand , says Fleming. A larger brain can protect against cognitive decline – if you assume cognition diminishes at some threshold of damage, then a bigger brain is going to succumb later.
It is feasible that brain shrinkage due to depression could raise the risk of this decline, says Fleming. But dementia is an umbrella term for a range of complex conditions associated with reduced brain function. Many factors can be involved, including inflammation and sticky protein plaques and tangles in the brains of people with Alzheimer’s disease, he says.
If future research robustly links brain shrinkage to depression, transcranial magnetic stimulation – using magnetic fields to stimulate specific areas of the brain – has been linked to , so it could be explored as a treatment, says Bijsterbosch.
“We hope that getting a clearer picture of the brain basis of depression will inform future work to understand individual differences and ultimately guide improvements in personalised treatment,” she says.
Nature Mental 91ɫƬ
