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At last scientists finally understand what makes antidepressants work

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Doctors have prescribed antidepressants for decades without fully understanding why they helped people. Yes, they increase serotonin levels in the brain, but a new study gives a clear picture of what else these drugs do to us.

Prozac and other major antidepressant drugs have helped people deal with clinical depression for decades, but the underlying mechanisms that allow the drugs to influence the activity of the brain's neurons weren't well understood. The end result was clear - the neurotransmitter serotonin tends to be deficient in depressive individuals, and antidepressants are able to boost serotonin levels, which helps relieve many of the anxiety and mood issues people with depression experience.

Most antidepressants don't show an immediate effect - instead, they take about three weeks to kick in. For the longest time, scientists couldn't actually explain this delay. They knew the antidepressants had to somehow "adapt" themselves to the neural pathways, but what that actually meant was anyone's guess. Now a team of French researchers have figured it out: antidepressants need three weeks to shut down a particular chemical regulator of microRNA.


This particular microRNA, designated miR-16, is in charge of making the serotonin transporter, and is generally found in the serotonergic neurons that produce serotonin. However, miR-16 is also found in neurons responsible for making the neurotransmitter noradrenaline. Here, miR-16 has precisely the opposite purpose - it completely blocks the production of serotonin in these neurons.


When drugs like Prozac go to work, they cause the serotonergic neurons to release signals. These signals cause the miR-16 to die off, which frees up the noradrenaline neurons to start making the serotonin transporter as well. Thus, Prozac both directly boosts the production of serotonin in the serotonergic neurons and indirectly causes the noradrenaline neurons to start making it as well.

It takes a little time for the miR-16 to be shut down enough for serotonin production to begin in earnest. That explains the three week delay between when a patient starts taking Prozac and first feels the effects of the drug. The researchers say the "plastic" properties of the noradrenaline neurons, in which they can alter their basic functions to help make more serotonin, is what's really crucial to Prozac's success.


[Science; image courtesy of Odile Kellermann.]