Brain Network Twice as Large in Depressed Individuals

Individuals with depression may have a brain network that is twice as large as those without the disorder, according to a new study published in Nature. Researchers from Weill Cornell Medicine believe their findings could identify those at risk of developing the condition.

Only modest differences in brain structure have previously been identified in depressed individuals

Depressive disorder affects roughly five percent of adults worldwide. The mental health condition is characterized by low mood, loss of pleasure in activities, poor concentration and low self-worth. Depression can be incredibly debilitating for individuals, affecting their work, home and social lives.

Gaining insight into how depression impacts the brain on a structural level is vital for deepening our understanding of the condition. In the past, neuroscientists have used functional magnetic resonance imaging (fMRI) to study brain activity patterns via changes in blood flow. This technique has enabled them to investigate brain organization on an individual level.

Decades of neuroimaging studies have found modest differences in brain structure and connectivity in patients with and without depression, struggling to identify mechanistic insights or risk factors for disease onset. However, many of these studies have failed to accommodate the periodic nature of the disorder.

“Depression is, by definition, an episodic psychiatric syndrome. It’s characterized by periods of low mood mixed in with periods of wellness,” said senior author Dr. Conor Liston, professor of psychiatry and neuroscience at Weill Cornell Medicine.

Depression-associated brain wiring is unaffected by mood

Over 140 people diagnosed with major depressive disorder were enrolled in the study, along with 37 healthy controls. The participant's brains were scanned using fMRI on multiple visits, up to 62 times, over 1.5 years. The researchers used precision functional mapping to assess differences in brain structure and connectivity between participants. The analysis was also replicated in multiple existing large datasets.

The researchers found one brain network, called the frontostriatal salience network, was almost two-fold larger in the brains of depressed participants compared to healthy controls. The salience network consists of several brain regions in the frontal cortex and the striatum and is believed to be involved in reward processing.

This expansion was also found to be stable over time, unaffected by whether the individual felt depressed or not in that moment. Although the size of the network didn’t change, the amount of brain activity between brain regions did vary depending on mood. Brain activity was decreased in participants who were actively depressed, and this lack of activity could predict whether a person would have a depressive episode in the following week.

Individuals may be pre-wired to develop depression

The original dataset was expanded to include hundreds of other patients whose brains were scanned less frequently. The researchers found that the differences in salience network topology were also discovered in children with no history of depression and may be able to predict the emergence of depressive symptoms in later life. In children as young as nine years old, the researchers were able to identify an increased salience network in those who would develop depression in their adolescence, compared to those who would not.

“Having a larger salience network appears to increase the risk for depression—the effect is an order of magnitude larger than what we usually see in fMRI studies,” said Dr. Liston.

Identifying individuals at risk

An increased frontostriatal salience network may serve as a potential biomarker for depression risk, aiding the identification of individuals who could benefit from early intervention.

“For years, many investigators assumed that brain networks look the same in everybody. But the findings in this work build on a growing body of research indicating that there are fundamental differences between individuals,” said lead author Dr. Charles Lynch, assistant professor of neuroscience in psychiatry at Weill Cornell Medicine.

The team aims to examine how different treatment options affect brain network activity in individuals with depression, with the goal of improving treatment strategies. They are also exploring whether the enlarged brain network may share characteristics with other mental health conditions that exhibit similar symptoms, such as bipolar disorder and obsessive-compulsive disorder.

Reference: Lynch CJ, Elbau IG, Ng T, et al. Frontostriatal salience network expansion in individuals in depression. Nature. 2024. doi: 10.1038/s41586-024-07805-2

This article is a rework of a press release issued by Springer Nature. Material has been edited for length and content.