“Every genetic ‘illness’ is a mismatch between an organism’s genome and its environment. In some cases the appropriate medical intervention to mitigate a disease might be to alter the environment.”
– Siddhartha Mukherjee, M.D.
Reader, when I find myself sitting with a patient who bares their soul and speaks of a terribly traumatizing life event, I often think of my grandfather. Born in Philadelphia in 1890, Abraham Kehr only attended eight years of school before dropping out to support his family—a choice many of his generation had to make. He went on to survive a mustard gas attack while serving our country in World War I, become a Golden Gloves boxing champion, and create a flourishing career as a businessman in his place of birth. While invariably my mind drifts to my grandfather’s qualities of tenacity and resilience when a patient describes their life on the brink of chaos, these attributes aren’t the primary reason I think of him. Rather, my thoughts center on my grandfather’s serene greenhouse, and the magnificent new species of hybrid orchids he successfully raised there by mixing the genotypes of different orchid species. He even named some of them after us grandkids! As a child, I used to assist him in tending to those orchids, which required a tender, loving touch. You see, while orchids are famous for their stunning beauty and diversity, they are infamous for the extremely delicate cultivation required of them. They require strong light, but not direct sunlight. They need high humidity and good air circulation—specifically around their roots. They need time to dry out, but also require heavy watering, mimicking drenching rainfall. And like Goldilocks, they need just the right temperature, between 50 and 85 degrees.
Why does my mind think of my grandfather’s greenhouse in times of stress? It reminds me that some individuals are like orchids—absolutely incredible, requiring just the right circumstances to truly thrive. Other individuals are like dandelions. Dandelions can grow just about anywhere—not even winter’s freezes can kill them. Give them a patch of soil with just the slightest hint of moisture, and their roots, thick and sturdy, can grow 15 feet deep. Some other individuals are like this, too—also incredible, capable of being just about the same steady person regardless of external factors. Humans are creatures of comparison, and here you may be saying to yourself, “well, it’s better to be like the dandelion, so I can withstand anything.” But genetics suggest we’d be wise to withhold judgement, for it is our very genes that determine whether we are orchids or dandelions—whether we can withstand severe trauma or succumb to it. And by understanding that our genes are a starting point, precision medicine combined with psychotherapy can do a better job helping patients to work through their stress, trauma, and PTSD in a way that makes sense in consideration of their unique physical and emotional natures. Today, I want to share with you a story that for some may be triggering. It illustrates the importance genetics can play in our mental health—and it may just give you hope for a brighter future of your own.
Nina* entered my office sobbing. She had been date-raped a few weeks earlier and had been referred to see me by a good friend of hers, Chelsea, who was a former patient of mine. Chelsea had left me a voicemail that Nina would be calling, so I already knew some of the details of what had happened to her. This first semester college sophomore was crying so hard she could barely breathe as I sat there in silence, looking at her with the deep sadness in my eyes that emanated from my heart.
Before too long I said to her, “Nina, Chelsea left me a voicemail about what was done to you, and I am so sorry this happened. When you feel ready, I am here to listen to your story.” When she was ready, she began to tell me her sad, horrifying tale. Nina had been introduced to her rapist a few weeks back by a sorority sister at a house party. He was very handsome, and she’d noticed a number of pretty girls had been talking to him—ones that she felt were much prettier than her. And yet he had focused his interest completely on her. As the other girls drifted away, she felt like she’d been swept off her feet. Over the next week or so he texted her every day, and let her know how pretty she was, and how he would like to see her again.
They met for coffee one time, then dinner a second time, and the third time he invited her back to his frat house after they had a number of beers and mixed drinks. He asked her if she would like a tour of the house and she readily agreed, feeling very special and highly desired. He took her into a remote area of the basement where they could be alone, and they began to make out, and then undressed to their underwear. Nina had second thoughts at this point, and told him she was uncomfortable and wanted to go upstairs. The guy then threw her down on a sofa, climbed on top of her, grabbed her throat with one hand, and said, “If you scream, nobody will hear you. Let’s just do it.” Given how drunk he was, and with his hand around her throat, Nina believed that he might kill her if she refused, and so she went along with it.
After it was over he rolled off her and was lying on the floor in a stupor. She quickly grabbed her clothes, ran upstairs and fled to a girlfriend’s apartment and told her the entire story. She also texted the sorority sister who had introduced her to the guy, telling her what happened also. They encouraged her to go to the police for a rape kit test, but she refused, feeling too ashamed and emotionally traumatized. In the days and weeks that followed she suffered from nightmares, flashbacks, panic attacks, crying spells, depression, self-loathing, suicidal feelings, and an inability to focus in class or on her homework assignments. Nina’s life had changed, and she felt like things might never be normal again.
Our first session was heavy as she told me her story. Gut and soul-wrenching. It was all I could do to keep from weeping myself, and I had to remind myself that this would be unempathic—would make it about my feelings instead of hers—and that my entire focus had to be on her emotional needs. Maintaining my composure, and after allowing the gravity of her words to sink in, I said to her, “Nina, you are suffering from PTSD and depression as a result of the terrifying and horrifying experiences in the basement of that frat house. What I believe will help you recover from this terrible event is some medication and talk therapy to help you get over the trauma. To prescribe the best medication for you, we can do a genetic test which takes about a week to come back, and in the meantime, I can prescribe something short-term, Alprazolam ER, to alleviate your anxiety and panic attacks. We should meet once a week for the talk therapy. What do you think of this plan?” She readily agreed, and a week later we met to go over her test results and begin to help her heal.
A Light at the End of the Tunnel: How SLC6A4, COMT, and CYP Genetic Testing can Help Trauma Survivors and Those Suffering from PTSD
Nina’s Genecept Assay results revealed two pharmacodynamic variants—SLC6A4 S/S and COMT Met/Met; and two pharmacokinetic variants—CYP2D6 and CYP2C19 with “Intermediate activity.” The pharmacotherapy of PTSD has the most studies supporting the use of SSRIs, and yet Nina’s SLC6A4 variant predicted a much higher rate of side effects and lack of effectiveness for this class of medications, so they would not be a good choice. An SNRI was therefore a better choice, and I settled on Desvenlafaxine (Pristiq) which is Venlafaxine (Effexor) after it passes through the liver. I also placed her on N-acetylcysteine (NAC) and Vitamin D to address her COMT Met/Met variant. (To learn about the specifics of these genes, I urge you to return to the chart summarizing Mental Health Genes, and how they work.)
Many of Nina’s acute symptoms in response to the rape began to resolve after one month on Desvenlafaxine, NAC and Vitamin D. This was a good place to start from a pharmaceutical standpoint—but privately, to myself, I worried about the longer-term effects of her SLC6A4 and COMT variants on her PTSD, as both predict a more severe response to trauma. Here’s why…
As I mentioned in the introduction, we humans can be thought of as “orchids” or “dandelions” in the face of stress—and it’s our stress-response genes that determine which category we fall into. Nina had two short alleles on her SLC6A4 gene. This genotype confers increased “serotonergic tone” (too much serotonin) in the amygdala of her brain where fear responses are processed, and thus she would have a higher than average fear response and greater response to stress, including a greater release of cortisol, with higher rates of anxiety and depression in response to traumatic stress. Conversely, she would thrive in a low stress environment, even flourish. In other words, Nina’s genes made her an “orchid”. Someone who is a “Dandelion” has a different genotype, and can therefore survive in harsh conditions—that is, high-stress environments. To add to Nina’s vulnerability, her COMT Met/Met variant would exacerbate the effects of her SLC6A4 gene. This variant is associated with “dopamine flooding” of the frontal lobes under stress, which results in increased anxiety levels and cognitive perseverating (ruminating over and over again about things)—also resulting in a higher stress response. Nina was genetically predisposed to her specific stress response—her very genes played a role in the way she felt in the moments, days, and weeks after her trauma. It wasn’t Nina’s fault—far from it. However, understanding her genetic profile meant we could specifically address her personal genome in a way that could bring about a better outcome for her.
Allowing an Orchid to Thrive: How “Orchids” Can Overcome their Personal Genome and Recover
Over the next two and a half years, I tried to provide Nina the right “temperature, humidity, and nutrients” to help this poor orchid survive, then grow again, through as much compassion and empathy that I could muster. At times Nina became quite suicidal, as the flashbacks would become more severe, and she began to feel a murderous rage toward the monster who had raped her. She would experience terrifying panic attacks, initially brought on when she learned that the sorority sister who had introduced her to the date-rapist had known that he’d had a history of misogyny and abusive behavior toward other young women prior to introducing Nina to him at that fateful party. Over the 30 months we worked together, I helped her work through filing a complaint against the rapist, surviving two hearings (one at her school and one in court), and unwinding the murderous effects of the rape on her heart, her soul, and her self-esteem. She left her sorority, which she felt was filled with largely unempathic, self-absorbed women, many of whom avoided her when they learned of her rape (a “Dandelion Environment”). With our patient, persistent, painstaking work the “Orchid Nina” began to emerge once again. She began working at a senior living center that was known for its caring culture for both residents and staff members (an “Orchid Environment”), and she fell in love with a really good guy. At the time she terminated therapy with me, they were talking about moving in together.
Reader—I share this story with you today because this type of trauma is back in the headlines. With the R. Kelly documentary, featuring dozens of his victims who he sexually assaulted for years, sending shock waves throughout the music industry and beyond, to the Award Shows reminding many of us of the #MeToo and #TimesUp Movements that Hollywood and other industries so desperately need to face. So many individuals are triggered and re-traumatized by these headlines, and may not understand the extent of their own pain or how to make it better, and so I hope that this blog, though horrifying in parts, can help point survivors in the right direction. Genetic testing to determine whether you are an “orchid” or a “dandelion” can help you understand why your reaction to trauma may differ from others around you. And it can certainly help doctors place you on treatment plans that will slowly allow you to mend. Be well, reader. There is a light at the end of the tunnel—there was for Nina, and it is my fervent hope that there will be light (and a return of lightness) for you, too.
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*Although lessons learned from the treatment of actual patients are included in the patient stories on this website and blogsite, the historical events and facts represented have been changed to protect the identities of any real patients and to protect their confidentiality. For example, the names, ages, careers, the number and sex of their children, as well as the careers of the patients’ parents have been deliberately altered, as well as other alterations that have been made. Consequently, all characters appearing on these sites are fictitious. Any resemblance to real persons, living or dead, is purely coincidental.