Brain Network Significantly Larger in People With Depression, Even in Childhood

Researchers have discovered that a brain network involved in reward processing and attention to stimuli is markedly bigger in people with depression, remains stable over time, is unaffected by mood changes, and can be detected in children before onset of depression symptoms.

Using a novel brain-mapping technique, researchers found that the frontostriatal salience network was expanded nearly twofold in the brains of most individuals studied with depression compared with controls.

“This expansion in cortex was trait-like, meaning it was stable over time and did not change as symptoms changed over time,” said lead author Charles Lynch, PhD, assistant professor of neuroscience, Department of Psychiatry, Weill Cornell Medicine in New York.

It could also be detected in children who later developed depression, suggesting it may serve as a biomarker of depression risk. Investigators said the findings could aid in prevention and early detection of depression, as well as the development of more personalized treatment.

The study was published online in Nature.

Prewired for Depression?

Precision functional mapping is a relatively new approach to brain mapping in individuals that uses large amounts of fMRI data from hours of scans per person. The technique has been used to show differences in brain networks between and in healthy individuals but had not been used to study brain networks in people with depression.

“We leveraged our large longitudinal datasets — with many hours of functional MRI scanning per subject — to construct individual-specific maps of functional brain networks in each patient using precision functional mapping, instead of relying on group average,” Dr. Lynch said.

In the primary analysis of 141 adults with major depression and 37 healthy controls, the frontostriatal salience network — which is involved in reward processing and attention to internal and external stimuli — was markedly larger in these individuals with depression.

“This is one of the first times these kinds of personalized maps have been created in individuals with depression, and this is how we first observed of the salience network being larger in individuals with depression,” Dr. Lynch said.

In four of the six individuals, the salience network was expanded more than twofold, outside the range observed in all 37 healthy controls. On average, the salience network occupied 73% more of the cortical surface relative to the average in healthy controls.

The findings were replicated using independent samples of repeatedly sampled individuals with depression and in large-scale group average data.

The expansion of the salience network did not change over time and was unaffected by changes in mood state.

“These observations led us to propose that instead of driving changes in depressive symptoms over time, salience network expansion may be a stable marker of risk for developing depression,” the study team wrote.

An analysis of brain scans from 57 children who went on to develop depressive symptoms during adolescence and an equal number of children who did not develop depressive symptoms supports this theory.

On average, the salience network occupied roughly 36% more of cortex in the children with no current or previous symptoms of depression at the time of their fMRI scans but who subsequently developed clinically significant symptoms of depression, relative to children with no depressive symptoms at any study time point, the researchers found.