Genetic Switch Involved in Depression (NIH news)

19 09 2012

The activity of a single gene sets in motion some of the brain changes seen in depression, according to a new study. The finding suggests a promising target for potential therapies.

People with major  depressive disorder, or major depression, have feelings of sadness, loss, anger  or frustration that interfere with daily life for weeks or longer. The symptoms  of depression also include memory loss and trouble thinking.

Past studies have found  that people with major depression have brains that are physically different  from those of non-depressed people. The depressed brain has a smaller  prefrontal cortex, a region at the front of the brain that handles emotion and  complicated thought. The area also has fewer and smaller neurons (nerve cells) in  the depressed brain.

To gain insight into  the neural mechanisms at work, a group led by Dr. Ronald Duman of Yale  University began with data collected in a previous study. They had done a comparison of postmortem brains from 15 depressed people and 15 non-depressed  people who were matched in age, ethnicity and gender. Using DNA  microarray chips to analyze the  activity of 20,000 genes, the researchers had found numerous genes that were  expressed (turned on and off) differently in the brains of depressed people.

For the new study,  the team focused specifically on genes related to synapses, the place where  signals pass from one neuron to another.  The work was funded in part by NIH’s National Institute  of Mental Health (NIMH) and National Center for Research Resources (NCRR). The  findings were published in the September 2012 issue of Nature Medicine.

Analysis revealed that about 30% of the genes with significantly lower expression in the depressed  brains related to some aspect of synapse function. Further experiments found  significantly reduced expression for 5 particular genes in the prefrontal cortex of depressed people.

The scientists searched for transcription factors—proteins  that bind to the DNA of other genes to turn them on or off—that were capable of  regulating the 5 genes. They found one  called GATA1 that is expressed significantly more in the brains of people with  major depressive disorder. Expression of the Gata1 gene in the prefrontal cortex was also higher in a  rat model of depression.

Raising expression  of Gata1 in cultured rat  neurons decreased the expression of synapse-related genes. It also decreased  the number of connections between neurons, supporting the idea that higher Gata1 expression can lead to the changes  seen in depressed brains.

The researchers next  tested the gene in rats and found that putting extra copies of Gata1 into their brains made them behave  as if they were depressed.

“We show that circuits normally involved in  emotion, as well as cognition, are disrupted when this single transcription  factor is activated,” Duman explains.

These findings may point toward a new target  for treatment. “We hope that by enhancing synaptic connections, either with  novel medications or behavioral interventions, we can develop more effective  antidepressant therapies,” says Duman.

— by Helen Fields


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25 09 2012
Genetic Switch Involved in Depression (NIH news) | West Coast TMS Institute | Scoop.it

[…] The activity of a single gene sets in motion some of the brain changes seen in depression, according to a new study. The finding suggests a promising target for potential therapies. People with maj…  […]

10 02 2013
West Coast TMS Institute | Genetic Switch Involved in Depression (NIH news)

[…] See on amirttl.wordpress.com […]

27 08 2013
Genetic Switch Involved in Depression (NIH news) | The LA Psychiatrist

[…] See on amirttl.wordpress.com […]

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