Researchers at Yale University in the USA may have found an explanation for why
patients with severe depression often show decreased volume of certain
areas of the brain.
Their study, published in the journal Nature Medicine, identified a genetic 'switch'
- a transcription factor - which regulates several genes related to the
communication between neurons. This transcription factor, called GATA1, appears
to be overproduced in depressed patients, say the scientists.
Senior author Professor Ronald Duman said the team 'wanted to test the idea
that stress causes a loss of brain synapses in humans'. Synapses are the
interfaces where two or more brain cells communicate. He says the study shows that
'circuits normally involved in emotion, as well as cognition, are disrupted
when this single transcription factor is activated'.
The researchers analysed post-mortem brain tissue of depressed and non-depressed
people donated from a brain bank. They found lower expressions of several genes
related to synaptic function, as well as fewer synapses, in a frontal region
of the brain of depressed people. They also found that the transcriptional
factor GATA1 was up-regulated in the depression group.
To test the relationship between GATA1 and brain volume, the scientists activated
the transcription factor in the frontal brain region of rats. Doing so led to a
decrease in expression of genes related to synapse function, causing the loss
of connection points between neurons. Also, the rodents started to display
depressive behaviour.
A link between the structural changes of the frontal brain region in
depressed patients and biological mechanisms needs further corroboration. The Yale
researchers believe the observed damage could be a result of chronic stress and
hope that their findings will lead to new treatments against depression.
'We hope that by enhancing synaptic connections, either with novel
medications or behavioural therapy, we can develop more effective
antidepressant therapies', said Professor Duman.
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