Popular Antidepressant May Reprogram Brain Genes

Reprogramming brain genes to treat depression may sound like something out of science fiction. But it turns out that we may have been doing it at least since 1992. That is the year the antidepressant Paxil was first marketed.

A new study suggests that at least part of the way that Paxil does its job is by changing how genes in the brain of a person with depression work. A team led by researchers at the Max Planck Institute of Psychiatry in Germany have found that the drug may help to erase some of the changes that have happened because of stress.

New Possibilities for Treating Depression

Now that we think depression might be treated by erasing stress from DNA, scientists could try to  design new drugs that might do the job better.

These latest findings also open up the possibility of a more personalized approach for treating depression. In the course of their work, the German researchers found a couple of different, related markers in blood cells that might predict how well a patient will respond to Paxil.

If other antidepressants work differently, then this biomarker may help doctors prescribe the right medicine after a simple blood test. Patients may get the help they need more quickly.

And even if all antidepressants work similarly, these studies may still give doctors a quick and easy way to determine how well a patient will respond to antidepressants. This could be an important tool for patient treatment.

Indirect Evidence

These studies didn’t look directly at what was happening in patients' brains. (Pulling out a patient’s brain tissue is way too invasive.)

Instead the researchers looked at what happens to cells and live mice in the lab and what happens to patients' DNA in their blood cells. All of these studies pointed to Paxil erasing some of the effects that stress can have on DNA.

How to Erase Stress

Paxil doesn’t reprogram brain genes by changing the underlying code of those genes. Instead, it changes how they work through epigenetics.

The idea is that stress can add small chemicals called methyl groups to DNA around key behavior genes. This causes the genes to become less active, leading to depression in some cases.

The thought is that Paxil makes some of the methyl groups disappear. Now these behavior genes are reactivated and the depression gets less severe.

But this drug does not restore the original genetic programming in the brain. Instead, it is able to reduce the amount of methylation in general. The stress-related depression is relieved as a result.

Stressed DNA

Part of the reason all those little methyl groups that decorate stressed DNA are there is because of something in the cell called DNMT1.

When a cell is stressed, DNMT1 goes into overdrive and starts adding extra methyl groups to the DNA at a faster rate than is normal. Over time, the DNA ends up extra methylated which may lead to depression.

This study showed that Paxil turns DNMT1 back down again. Over time the number of methyl groups on the DNA drops, eventually leading to less depression. Or at least that is the theory.

Much more work needs to be done to confirm this but if true, these results could have wide-ranging effects on treating depression.