What I Learned About My Depression From My DNA

September 4th 2016

Andrew Rose

It never seemed odd to me to be a nine-year-old boy taking a daily dose of Prozac or Lexapro, squeezed like an overripe pimple from one of the drug company’s sample blister-packs.

What should have been more notable at the time was that, despite taking some variety of SSRI antidepressant from the time I was in elementary school through college, I never felt much specific benefit from any of them.

It wasn’t until I became intensely depressed—even by my own vertiginously gloomy standards—after my sophomore year in college, and started taking a drug called lamotrigine that I began to feel some relief. But eventually even the lamotrigine ceased to be enough, and my psychiatrist added lithium to the mix. (Lithium deserves its own lengthy discussion; suffice it to say that, as elementary particles go, Li is up there with O and H in my book.)

It wouldn’t be the last time that I would have to disrupt my pharmaceutical regimen—adding drugs to help with sleep, to further bolster my perilously weak mood, and even a few “atypical” antipsychotics, which always made me some combination of ravenously hungry, cognitively impaired, and acne-ridden. Psychiatry had about a 51 percent success rate in providing drugs that treated my symptoms without bringing disruptive side effects along for the ride. While I have sometimes been frustrated by the hit-or-miss nature of modern pharmaceutical “polytherapy,” I know how comparatively fortunate I’ve been to have had so many different options.


Last year I decided to move back to the Northwest after ten years on the East Coast. After a bumpy landing on my return from New York, I found a job in Portland at a university and teaching hospital. One of the biggest perks of my position as an administrative assistant is the health insurance, whose fairly reasonable out-of-pocket costs are negotiated through our union.

By now, I’ve found every type of specialist I need at the university, but the first appointment I made was with a new psychiatrist. Dr. R is a younger woman whose voice bears a light dusting of her highly-educated Texan upbringing, and who has an infectious enthusiasm for the healing power of companion animals. Personality aside, on our first meeting she took a detailed history (I would later find out she served as Chief Resident in the Department of Psychiatry before taking a faculty position), and after asking several follow-up questions said that, because I had such a complicated history with psychotropic meds, I should consider having my DNA tested. After a few painless swabs inside my cheek and some paperwork, a personal artifact more telling than every minute in the psychiatrist’s chamber was on its way to be decoded.


Genetic testing as a tool for pharmaceutical treatment is a relatively new phenomenon that is growing in popularity. While the process of sampling DNA in order to anticipate favorable or unfavorable drug reactions is still relatively new, the potential benefits of more targeted therapy are immense. Katarzyna Drozda, Daniel J. Müller, and Jeffrey R. Bishop write in a 2014 article in the journal Pharmacotherapy that, despite certain reservations, the future of genetic testing is encouraging, and “any added knowledge that can help clinicians optimize the risk:benefit ratios of our available treatments has tremendous potential for improving the lives of patients.” Starting in the 1950s, longitudinal studies of the genes of patients taking first-generation antidepressants began the process of understanding which genetic markers might influence a person’s metabolism of a given drug.

The latest genetic tests are more likely to be covered by insurance and cover a wide variety of genetic markers. Many, including the authors of the Pharmacotherapy review, remain somewhat skeptical, and believe that more data are needed to assess the widespread reliability of genetic testing for neuropsychiatric drugs. While generally optimistic, Drozdal et al note that genes alone are never solely responsible for psychiatric conditions, and thus cannot be the only arbiter of treatment decisions. Antidepressants and other psychotropics are not the first medical treatment to benefit greatly from the use of DNA sampling: breast and ovarian cancer can often be predicted through examining mutations in genes like BRCA1 and BRCA2. Using DNA to guide neuropsychiatric practice needs more time to mature as a diagnostic tool, but it is already quite impressive as the biggest advancement in psychiatric diagnosis since the Rorschach Test.


My newly minted faith in the mission of our research institution sustained me as I put my hope in science. Medicine could be quantified; every molten droplet of unignorable depression might leap from my body in fear of the best chemical cure. This faith was essential, but hard to sustain as I tumbled deeper into an emotional void.

By the time Dr. R called me at work with the results of the DNA “Interpretive Report,” I had already emailed her about the drastic state of my mood. When we spoke, she had the breathless, pleasantly satisfied tone of someone for whom being proven right also means being able to help someone else. The results were too long to explain through the confidential online patient communication portal, but she wanted to reassure me that I had short serotonin alleles, among other revelations, and that there was hope in pharmacology.

What I learned in this five minute phone conversation was more definitive and more useful than the millions of milligrams of Big Pharma’s products I’d experimented with for decades. The report confirmed some things I’d long suspected, and it gave reason and depth to my pharmaceutical self in a way that showed how hollow all previous attempts at explanation had been. When we met at her office a few days later, Dr. R. gave me the report with the first item broadly and excitedly highlighted:

  1. CYP2D6 phenotype: ULTRA RAPID METABOLIZER This statement isn’t quite as clear and straightforward as it first appears. Just kidding; genetics is very confusing. Being an ultra-rapid metabolizer means that I am at risk of overdose with some medications called “prodrugs,” where my body could make me sick by producing too much of the active metabolite. On the other hand, there are what the report calls “active” drugs, which I would metabolize too quickly and get a potentially sub-therapeutic dose. Apparently this means I should avoid oxycodone in favor of certain synthetic drugs like hydromorphone, among many other substitutes the report suggests.
  2. SLC6A4 phenotype: INTERMEDIATE RESPONDER Carriers of S or LG alleles may have decreased serotonin transporter expression compared to LA/LA subjects. Possible risk or slower response to SSRIs or increased risk of adverse events. So there’s a reason I could pop Prozac like bland Pez and still be suicidally depressed half the time! The history of psychiatry is riddled with unenlightened attempts being nudged out by the only slightly more enlightened medical model du jour. Yet instead of my failure with SSRIs being either a reason to label me bipolar, or just more evidence of my pathological inability to get better, I finally had something approaching an explanation.
  3. COMT phenotype: HIGH ACTIVITY The COMT Val/Val genotype results in… decreased dopamine levels in the prefrontal cortex. …Val/Val patients with depression are less likely to achieve remission when treated with SSRI antidepressants… Val/Val patients may benefit from agents that increase dopamine availability including methylphenidate and amphetamine. Another, separate, blow to my years of pharma trial and error. Not only was I not responding to SSRIs because the dose was too low, but there was another genetic factor affecting my mood. Chronic shortages of dopamine have been a major contributor to my depression, and many other symptoms that are finally being addressed with the right medication. It’s been a sometimes Sisyphean slog through countless meds, but I’m getting closer to the ideal balance.
  4. This test should not be used as the sole means of treatment decision making… The report—six pages of results interspersed with interpretations and recommendations for medication choices—reads as if the Oracle at Delphi had a centrifuge and a laser printer. While I’ve rarely felt disappointed with any among the parade of MDs, NPs, PAs, and Ph.D.s who’ve treated my disheveled mood and its tricky attempts to evade understanding over the years, I can’t help but wonder what my life would have been like if my parents had been given this knowledge twenty years ago. Because of the profusion of pharmaceutical science and new remedies, the process of finding the right psychotropic drug may be getting more complex and time-consuming. The promise of genetic testing is to provide a clearer and more direct path through the thicket of research, discovery, marketing, and anecdote that usually drive prescribing choices.

What did I learn from my own DNA? Just as unwrapping a breakfast sausage link and examining its contents will not reveal how the meaty treat was made, merely naming and analyzing someone’s genetic material cannot reveal the full scope of their personal agonies and triumphs. However the information that this simple test contained is truly mind-blowing. To say that DNA is an amazing scientific discovery with limitless potential for explaining life on earth is obvious, but to a person who has struggled for years with one of modern medicine’s least-understood disciplines, being able to have even a little clarity in treatment decisions is revelatory. DNA after all is not just a static inscription of one's material presence, it is also a map that can help chart new frontiers of existence.