Major depressive disorder, commonly referred to as depression, is a debilitating psychiatric disorder estimated to affect roughly 5% of the global population. Depression is characterized by persistent sadness and hopelessness, difficulty concentrating on tasks, a lack of interest in everyday activities and changes in sleep and/or appetite.
While past studies have shed light on some of the factors that can contribute to the emergence of depression, the neural processes and brain changes associated with this disorder have not yet been fully elucidated. Better understanding how depression affects the brain could potentially guide the development of new tools and strategies for diagnosing or treating it.
Past research has linked depression with changes in various brain regions, including a reduction in the volume of gray matter in the hippocampus and frontal cortex. While earlier studies have provided some interesting insights, their findings were often inconsistent or inconclusive.
Researchers at Washington University School of Medicine analyzed thousands of brain scans collected from a population sample, including people with subclinical symptoms. The results of their analyses, published in Nature Mental Health, identified various changes in the brain that appear to be associated with depression, some of which are inconsistent with earlier observations.
“Determining how the brain changes in people with depression has been a longstanding scientific goal that many papers have tried to answer,” Janine D. Bijsterbosch, the paper’s senior author, told Medical Xpress.
“Despite substantial existing work, studies designed to identify agreement between previous studies (so-called ‘meta-analyses’) sometimes struggle to find consistent evidence for depression-related brain changes. Furthermore, prior studies often focus on target brain systems likely to be involved in depression and may therefore overlook findings in other parts of the brain (e.g., as suggested in our prior work).”
The analysis of over 23,000 brain scans
The main goal of the study by Bijsterbosch and her collaborators was to improve the current understanding of depression and how it is reflected in the brain. To do this, the researchers analyzed six available datasets individually and then compared the results they attained.
“We wanted to see if a whole-brain approach using big datasets would help to find more consistent evidence of brain changes linked to depression,” explained Bijsterbosch.
“We used six big datasets covering the full lifespan that ranged from 185 to 11,000 participants per dataset. Each dataset was analyzed separately to relate summary indices of brain structure and function to depression measures (of severity and personality-based risk). The results were then combined across the six datasets.”
Consistent with earlier research, the researchers found that depression was linked to a reduction in gray matter in three brain regions: the frontal cortex, anterior cingulate cortex and insula. These areas of the brain are known to play a role in the regulation of emotions, decision-making, motivation and the internal processing of bodily sensations.
“A key surprising finding was that smaller brain regions in motor and visual regions were linked to higher levels of depression,” said Bijsterbosch. “It has been known that reduced brain size in other (e.g., frontal) parts of the brain is linked to depression, but the location of these new results was surprising because we don’t usually link symptoms of depression to sensory processing or motor action.”
Earlier research had also linked depression to changes in regions in the basal brain, such as the amygdala and hippocampus. Bijsterbosch and her colleagues, however, observed little evidence of this. It is possible that this discrepancy is linked to the population datasets that were used, which do not tend to include patients with high levels of depression severity.
Toward a better understanding of depression
This study was one of the most detailed and comprehensive explorations of brain changes associated with depression to date. Overall, its findings suggest that depression affects a broad network of brain regions that have been implicated in important mental functions.
The team’s efforts could soon inform further studies exploring how the uncovered brain changes could relate to specific symptoms of depression. Eventually, they could help paint a clearer picture of this common mental health disorder, potentially also informing the development of promising new diagnostic tools or treatments.
“One of the first authors of our paper, Kassandra Hamilton, is currently planning a follow-up study to test whether visual and motor regions encode specific symptoms of depression,” added Bijsterbosch.