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Depression hits genetic switch to disrupt brain cells

20 August 2012
Appeared in BioNews 669

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.

Decreased expression of synapse-related genes and loss of synapses in major depressive disorder
Nature Medicine |  12 August 2012
Depression, Stress Linked With Brain Shrinkage - Here's Why
Huffington Post |  13 August 2012
How depression shrinks the brain
CBS News |  13 August 2012
How stress and depression can shrink the brain
Mail Online |  13 August 2012
Yale team discovers how stress and depression can shrink the brain
EurekAlert! (press release) |  12 August 2012
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