Your brain looks different if you have depression. But many of the differences seem to be caused by depression, rather than precede it.
When neuroscientists compare the brains of people with and without depression, there are common dissimilarities. For example, people with depression tend to have a smaller hippocampus, a brain region important in forming memories.
But it has been difficult to work out whether such differences cause the symptoms of depression or whether they result from the disorder, says Heather Whalley at the University of Edinburgh, UK. 鈥淲e don鈥檛 know which causes which.鈥�
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To answer the question, Whalley and her colleagues turned to two huge genetic databases. Consumer genetic testing company 23andMe holds information on the DNA and depressive symptoms of tens of thousands of individuals, and the UK Biobank collects DNA, lifestyle and behaviour questionnaires and brain scans from thousands more.
Whalley and her colleagues used this data, as well as already-published research, to create what is known as a polygenic risk score (PRS) for depression. A PRS assigns weight to various genetic factors that are thought to contribute to the risk of a condition. They made sure their PRS worked by testing it in a separate sample of 11,214 people.
The team then assessed the brain scans and behaviour records of those individuals with a PRS that put them at a genetic risk of depression. They found that people with higher genetic risk scores tended to have less white matter in their brains, and that it didn鈥檛 seem to be functioning as well.
Whalley and her colleagues then used a statistical analysis to work out whether these white matter differences were causing the depression or resulting from it. The analysis takes into account brain structure and depression symptoms, and looks at how closely each are related to genetic factors. Genes are present from birth, so if genetic factors are more closely linked to symptoms, for example, that suggests that the symptoms were present before the brain structure differences.
The team found that many brain differences appear to be caused by depression. But differences in a region of the brain called the anterior thalamic radiation appear to come before depression.
This suggests that the genes that put a person at risk of depression do so via this particular brain network. 鈥淚t does make sense,鈥� says Whalley. 鈥淚t鈥檚 the main relay centre鈥or information going to and from the brain.鈥�
Depression symptoms and behaviours could end up impacting the brain鈥檚 white matter connections more generally, says Maxime Taquet at the University of Oxford, who wasn鈥檛 involved in the study. 鈥淚t might be that patients with depression鈥� do not use some of the brain connections that other people would use,鈥� he says.
Being socially withdrawn, or focusing more on the negative than the positive, could have an effect, he says. 鈥淲e know that if we don鈥檛 use a pathway in the brain, that pathway starts to shrink.鈥�
Whalley鈥檚 team also found a host of lifestyle factors and experiences that seem to be linked to depression. They found that a combination of childhood trauma and poverty put individuals at the greatest risk of depression.
While childhood trauma was a risk factor in causing depression, trauma in adulthood wasn鈥檛. Experiencing high levels of stress at a young age can disrupt a person鈥檚 stress coping mechanisms for life, says Whalley. 鈥淚t might mean that you鈥檒l need a smaller trigger to have a much more stressful response,鈥� she says.
鈥淚t鈥檚 a marvellous paper,鈥� says Myrna Weissman at Columbia University in New York. Weissman plans to look for those white matter differences that seem to precede depression in her own research into families at risk of the condition. 鈥淚t could be another way of identifying individuals at risk [of depression] using biological markers,鈥� she says.
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