depression
Neuroscientists from the Massachusetts Institute of Technology (MIT) published a study that says that making decisions in a cost-benefit conflict, which is a situation where both outcomes could lead to both favorable and unfavorable results, is affected heavily by chronic stress. Reuters

For the past many years Prozac and Zoloft have helped many fight depression, but one of the major drawbacks of these pills — collectively known as selective serotonin reuptake inhibitors (SSRIs) — is the time it takes for them to take effect. Most SSRIs can take weeks to start showing any effect, and in some cases may even take longer.

Now for the first time, a team of Rockefeller scientists has described how SSRIs initiate their action by targeting a particular type of nerve cell, a finding which they said may herald a new type of antidepressants that will not only act much quicker than the existing ones but will also be safer.

Their findings was published last week in Neuron under the title "Initiation of Behavioral Response to Antidepressants by Cholecystokinin Neurons of the Dentate Gyrus."

Lucian Medrihan, a research associate in the lab of neuroscientist and Nobel laureate Paul Greengard who led the study, said: “While existing SSRIs can produce moderate effects within hours or even minutes, most people don't really begin to feel better until they've been on the drugs for a significant amount of time—a major drawback when it comes to treating clinical depression.”

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Most of these anti-depressants facilitate increased access of serotonin to nerve cells; serotonin is a neurotransmitter that helps the brain regulate certain emotions.

When a neuron releases serotonin to signal another cell, it normally reabsorbs excess amounts of the neurotransmitter, preventing it from lingering in the junction between two neurons. SSRIs prolong this signal by curbing the absorption of the excess serotonin.

What happens next is still something that neuroscientists are working hard to find out, as neurons get affected in different ways to this surge in serotonin; some get triggered while some calm down.

"That's because there are 14 types of serotonin receptors present in various combinations in different neurons," says Yotam Sagi, a senior research associate in Greengard's lab.

The study set out to identify “the earliest molecular steps by which SSRIs curb depression.”

To narrow down their search, Medrihan and Sagi focused on a particular group of cells called cholecystokinin (CCK)-expressing neurons in the part of the brain known as the dentate gyrus. The researchers suspected that this group of cells was affected by SSRI-induced serotonin changes.

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Using a technique developed at Rockefeller called "translating ribosome affinity purification," the researchers were able to identify the serotonin receptors present on CCK cells.

"We were able to show that one type of receptor, called 5-HT2A, is important for SSRIs' long-term effect," Sagi said. "While the other, 5-HT1B, mediates the initiation of their effect."

The researchers said identifying CCK neurons in the dentate gyrus as the site of interest, will advance scientists' understanding of how SSRIs work. "It should also facilitate development of new classes of potent and selective drugs," Greengard said.

According to a Time report, about 12 per cent of Americans took antidepressants, and 6.7 percent U.S. adults are affected by clinical depression.

“ It is costing the U.S. economy alone $210 billion a year in lost productivity, missed days of work and care for the many physical and mental illnesses related to depression, like anxiety, posttraumatic stress disorder, migraines and sleep disorders,” the report said.

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