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.

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9 thoughts on “Genetic markers show his fight against depression uphill battle

  1. Very interesting, helpful information regarding the physiology behind the highways all these chemicals must travel & what happens if they detour. Glad to know they are educating you as well as treating you. Hope your spirits are lifted as you feel the love, prayer, support & encouragement we all are sending your was as well as to Barclay & the children.

  2. Hey Jack. Very interesting reading, and even though the news is not great, I would not get that down about it. You have a better idea of what is going on but the science is not exact…not even close. There is so much we still have to learn about the brain, and, in some cases, there are back up mechanisms that kick in. Also, many have explained to me that genetics accounts for about 30 percent of what happens to us, which leaves 70 percent to fight back. Lithium is a great medicine, and many of the doctors I have known believe it is the best when you find the right dose. So there is plenty of hope and plenty to look forward to as you continue your journey. And, by the way, AU just kicked some Ole Miss butt! See you soon. MJ

  3. This article could have been written by my brother….his has been a long hard battle, Lithium is the only drug that seems to help. I also have an aunt on Lithium…I lost my oldest son because I couldn’t keep him on his meds…prayers for you in your battle…I am going to talk to my family about this test.

  4. This is such a great article Jack, and I feel like with every post to your blog you are changing lives. We are praying for you and your precious family…always. It seems like you are in great hands at the clinic, and amazing hands from heaven.

  5. Jack, your are undoubtedly one the bravest persons I know. I had a family member who suffered from depression and it was stigmatized. FIGHT ON JACK!!!

  6. Great article. I never had this test performed, however, three of your examples were glaringly reminiscent of what I went through. The failure of SSRIs to work and the disastrous side-effects. The failure of the tricyclics to offer any relief and the impulse control issues. Even though the medications that I take currently, (and have taken for the past three years), are working wonderfully, it is comforting to see evidence of what I always knew: that it is beyond our control – an illness and not a choice; not lack of will-power; nor lack of self-control, etc.

    Thank you, Jack for the courage to share what you are going through. Your courage gives me the courage to share as I am sure it does others.

  7. Mike,
    My first reaction when told the genetic test results was to cry. It was as if someone finally said it wasn’t all in my imagination, so I can relate somewhat to your emotions.

  8. Dear Jack,
    I knew your wonderful parents very well as I grew up in Eufaula. Your mother taught
    me and my identical twin, Anne, World History at Huntingdon College in Montgomery.
    Blogs such as yours are so needed;keep up the good work. The two books that I have
    found most helpful are Blake Levine’s, Beating Bipolar, and Dr. Jamison’s book,The Unquiet Mind.
    Perhaps you, Anne, and I could meet for lunch at the Amsterdam restaurant in Auburn. We need to discuss the National Alliance for the Mentally Ill and what a strong chapter could mean for this area. My phone number is 745-5986 and a get
    emails at my sister’s email address,
    Warmest regards,
    Carolyn Bennett Dunaway

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