Individuals with depression may have a brain network that is twice as large as those without the disorder, according to a study published in Nature. Researchers from Weill Cornell Medicine believe their findings could lead to identifying those at risk of developing depression early on.
Depressive disorder affects roughly five percent of adults worldwide, causing symptoms such as low mood, lack of pleasure in activities, poor concentration, and low self-worth. Understanding how depression impacts the brain structurally is crucial for advancing our knowledge of the condition.
Using functional magnetic resonance imaging (fMRI), neuroscientists have previously found modest differences in brain structure and connectivity between individuals with and without depression. However, many studies have struggled to offer mechanistic insights or identify risk factors for disease onset, often failing to accommodate the episodic nature of depression.
“Depression is, by definition, an episodic psychiatric syndrome characterized by periods of low mood mixed with periods of wellness,” said Dr. Conor Liston, senior author and professor of psychiatry and neuroscience at Weill Cornell Medicine.
The study involved over 140 participants with major depressive disorder and 37 healthy controls. Participants’ brains were scanned using fMRI up to 62 times over 1.5 years. The researchers employed precision functional mapping (PFM), a technique that estimates metrics of brain function using large volumes of fMRI data over time.
The study uncovered a brain network called the frontostriatal salience network that was nearly twofold larger in those with depression compared to healthy controls. This network includes regions in the frontal cortex and striatum involved in reward processing. Interestingly, this expansion was stable over time and remained unaffected by the individuals’ current mood. However, brain activity within the network did vary with mood, showing decreased activity during depressive episodes and potentially predicting future depressive bouts.
Further, the research expanded to include hundreds of additional patients and identified similar network enlargements in children with no history of depression. This suggests that individuals may be pre-wired to develop depression. Even in children as young as nine, an increased salience network size could predict the onset of depression in adolescence.
“Having a larger salience network appears to increase the risk for depression—it’s an effect an order of magnitude larger than what we usually see in fMRI studies,” Dr. Liston explained.
Lead author Dr. Charles Lynch, assistant professor of neuroscience in psychiatry at Weill Cornell Medicine, added, “For years, many investigators assumed that brain networks look the same in everybody. But our findings build on research indicating fundamental differences between individuals.”
The team aims to explore how different treatments affect brain network activities in those with depression, with the goal of improving treatment strategies. They are also investigating if the enlarged brain network might share traits with other mental health conditions, such as bipolar disorder and obsessive-compulsive disorder.
In sum, this study highlights the potential of an enlarged frontostriatal salience network as a biomarker for depression risk, paving the way for early intervention strategies and tailored treatments for those at risk.
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.