Depression, a widespread and debilitating condition affecting millions worldwide, has long puzzled researchers with its complex and varied manifestations.
As current treatments prove ineffective for up to 30% of patients, the need for deeper insights into depression's underlying mechanisms and novel therapeutic approaches becomes increasingly urgent.
A study conducted by the Netherlands Institute for Neuroscience sheds new light on the disease, revealing a surprising connection between depression and microglial cells in the brain.
Prior research has hinted at the involvement of inflammatory markers in depression, with the condition often linked to chronic inflammatory diseases like rheumatism, inflammatory bowel disease, and multiple sclerosis.
These findings have raised speculation that brain inflammation might play a role in depression. However, the recent study challenges this assumption by unearthing a different phenomenon.
The researchers worked with post-mortem human brain tissue
Led by Karel Scheepstra and supervised by Inge Huitinga and Jörg Hamann, the research team examined post-mortem human brain tissue from individuals diagnosed with depression.
The brain tissue samples were generously donated to the Dutch Bran Bank for Psychiatry (NHB-Psy) by recently deceased individuals, provising invaluable insights into the neurological basis of depression.
Remarkable, the study discovered that a specific type of immune cells called microglial cells exhibited reduced activity in people with depression, contrary to expectations.
These microglial cells are crucial for maintaining synaptic connections between neurons, facilitating efficient communication within the brain. Additionally, microglial cells continuously scan the central nervous system for damaged neurons, synapses, and pathogens.
Upon closer examination, the researchers found that only microglial cells located near neurons showed diminished activity in depressed individuals. This observation led the team to investigate whether neurons communicate with microglial cells during depression, leading to their suppressed state.
Their hypothesis proved to be correct
Scheepstra, who worked as a reseracher and psychiatrist at Amsterdam UMC, explained the findings, "We used fresh tissue immediately after death to isolate microglia and compared these between depressed people and controls. We saw abnormal microglia in depressed patients, with the greatest abnormalities seen in patients who were most depressed just before death.
"Interestingly, abnormalities were only seen in the gray matter and not in the white matter of the brain. This suggests that there is a likely interaction between the microglia and the structures located in the gray matter: the neurons and synapses."
The study also shed light on the role of specific proteins, CD200 and CD47, present on brain cells and synapses, which interact with microglial cells, signaling a "don't eat me" response.
These proteins were elevated in depressed individuals, resulting in suppressed microglia and potentially hindering their ability to clear damaged neural connections.
The concept of neuroplasticity, the brain's ability to form new connections between neurons, is thought to be disrupted in depression. The researchers speculate that the altered interaction between neurons and microglial cells may play a role in this process.