October 5, 2013

Genetic markers show his fight against depression uphill battle

By Jack Smith

Part of me was stoic. Part of me was sad. Part of me wanted to cry.

And part of me wanted to go all Eminem, untuck my shirt with a snatch, pull my denim jeans down to my hips and yell, “I told ya’ll somethin’ ain't right!”

That’s how I felt when the doctor reviewed the results of my genetic profile, a “personalized medicine” test from Genomind.

The test looks at 10 genes related to psychiatric conditions. The results can give the doctors an idea of what’s going on with the patient’s brain chemistry and metabolism. It also tells doctors what drugs will and won’t work.

My results weren’t pretty. The average patient at this renowned clinic has 1 or 2 genetic mutations picked up by the test. I had five.

I want to share them so others struggling with mental illness can understand what can be learned from this emerging science.

#1: Serotonin Transporter (SLC6A4)

According to Genomind, the serotonin transporter is a protein that controls the levels of serotonin in the brain. Individuals like me with a mutation in this gene have a reduced ability to move serotonin on the brain’s neural highway. In turn, the neurons have trouble communicating with each other, causing serotonin to back up in the brain instead of going where it’s supposed to go.

The bad news for patients with this mutation is many of the SSRI depressants on the market won’t help them. They also suffer more pronounced drug side effects because their brain can’t process the chemicals correctly­. A double whammy.

#2: Serotonin Receptor (5HT2C)

The serotonin receptor molecule plays an important role in signaling to the body that it’s had enough food. This is my new excuse for eating two desserts.  This receptor mutation can also block the activity of serotonin, adding more types of antidepressants to the list of drugs that won’t help. Interestingly, this mutation can also have an adverse impact on cholesterol levels. Mine was 280 last week when checked. Must be all that Blue Bell.


This one creates a problem with more of the brain’s natural happy juice, dopamine and norepinephrine. COMT is an enzyme that acts as Air Traffic Control for dopamine. Only nobody is home in my ATC tower.

This can be problematic, because those two chemicals “are critical for memory, attention, judgment and other executive functions,” according to Genomind.  (That at least explains me impulse purchases).

People with this mutation can have increased dopamine breakdown, which results in a lower level of the chemical in the brain’s frontal lobe.  That can cause depression.

CYP Enzyme (2D6)

The bulk of antidepressants go through this system, which is sort of like the garbageman of the liver.  The CYP enzyme controls how quickly the body metabolizes drugs. The report indicated my genetic mutation means I’m not efficient at metabolizing a certain class of antidepressants, causing them to clog up the drain. Like the serotonin Transporter mutation, that can mean you suffer strong side effects without reaping the reward of drugs.

CYP Enzyme (2C19)

This particular mutation means I am an “ultra-rapid metabolizer” of tricyclic antidepressants. Examples of tricyclics are Lexapro, Selexa, Elavil and Valium. I have taken all four. And none would have helped. The doctor says my body “incinerates” those drugs and renders them impotent.

So what does this all mean? I’m not sure yet, except that we plan to optimize lithium as a key weapon in my war on depression. A lot of the other options are now seemingly off the table.

The good news is we know what won’t work. Emotionally, I have peace knowing there is an explanation for my repeated relapses and all the failed attempts to get better. It really wasn’t anything I did wrong.

I’ve shared all this in hopes that it will help others navigating the stormy seas of mental illness. I’ve learned that as the patient, it’s important to be your own advocate and to be aggressive. Two different doctors I’ve seen in a month opted not to offer this test and planned to put me on meds that we now know had no chance of working.

Research the Genomind DNA test. Don’t just ask your doctor about it. Pshychiatrists’ offices are flooded with patients, and patients can’t possibly get a quality diagnosis in one 30-minute visit.

Tell your doctor you want this test done. If he or she isn’t willing to help or can’t offer the test for some reason, go somewhere that can.

Until next time, grace and peace to all. I will continue to pray for my comrades embroiled in the fight of their lives.

I look forward to sharing my diagnosis when all the puzzle pieces are in place.