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    Self-Saboteur, Gene by Gene, on the Global Stage How Denial, Delay in Seeking Help, and Personal Genomic Uncertainty Can Sabotage One’s Life

    “The impulses, ambitions, fantasies, and desires that drive human history are, at least in part, encoded in the human genome.”

                        –  Siddhartha Mukherjee, M.D.

    Reader, it’s the dead of winter and flu season has officially arrived. If it’s not the flu, it’s a cold, or a sinus infection, or an upper respiratory tract infection—the bacteria and viruses in the air are so prevalent this time of year they’ll arrive at your doorstep (or rather in your lungs!) before you even have time to utter those most-feared words… “I think I’m sick.” But I have a question for you—when you’re sick, do you see a doctor? And if not, what’s your rationale? I know plenty of people who get their runny noses to the urgent care as soon the fatigue hits, and plenty who try to “ride it out” and let the sickness run its course. But what if you’ve been sick for a long time—not days, or even weeks, but months or years? Decades? I will be the first to admit that “visiting the doctor” is not as simple as it seems. Many of us have complex but firm beliefs and unconscious biases toward or against the practice of medicine or its alternatives—and the labyrinthine nature of our country’s health care system only adds to that complexity. But when you’ve been feeling unwell for a long period of time and have not sought treatment, there’s a good chance something else may be motivating your decision—fear. Today, I want to share with you something you may not want to hear: if you’ve not felt well for a long time and have refused to seek help, you may be self-sabotaging your wellbeing.

    That’s why I want to tell you about a patient of mine named Sam. Sam suffered from anxiety for years but did not address it until it was almost too late. Let’s dig into his story—and look at how precision medicine and genetic testing helped him out of the dark hole into which he’d been falling for a long, long time.

    Sam’s Story: How Untreated Anxiety Almost Derailed a Career

    Reader, Sam* is special. A thoughtful, highly intelligent, articulate, and soft-spoken national security expert and former White House Senior Official, this 67-year-old man had crystal clear blue eyes and a slight southern drawl. During our first meeting, he introduced himself in a somewhat restrained and formal fashion and began to tell me his story. “Dr. Kehr, my internist strongly urged me to see you for a mental health evaluation. He has been encouraging me to do so for some time now, and I can no longer resist him. I held out as long as I could, because in my world involving global politics, some believe that seeing a psychiatrist is a career-limiting step. Now that I am retired, I am no longer concerned about my colleagues’ perceptions. And I’m interested in what you might have to say.”

    During his career Sam had traveled to more than 100 countries on official government business, meeting Heads of State in many of them, and had been responsible for some very sensitive discussions and negotiations. I could see why past Presidents had relied upon him—he was quietly confident, brilliant, and just so likeable as a human being. He had also had some stints as a senior executive in Fortune 500 companies during his long and storied career. However, Sam had become a shadow of his former self—his anxiety was so palpable that sitting with him actually made me feel anxious too (really!), and this countertransference reaction of mine helped me empathize with Sam more effectively. He had withdrawn from family and friends, had given up his global advising and consulting opportunities, and spent increasing amounts of time at home watching cable news and reading 5 newspapers a day. What a waste of a national treasure!

    I’d encountered patients like Sam before. He tried for years to pretend nothing was wrong, but after talking with him, it was clear he suffered from anxiety, to the point that it had become debilitating. I understand why high achievers like Sam put off treatment for years: an undiagnosed issue is a lot easier to ignore. But once you put a name to an illness, the game of pretend ceases—if you don’t seek treatment at that stage, it’s a conscious choice… one that may be difficult to come to terms with. Treatment for any illness—but especially for mental illness—can cause changes to your lifestyle and to your self-concept. Sam was afraid of those changes—he was afraid treatment would hold him back. In fact, it was the opposite: his lack of treatment had limited his potential and was slowly corroding his life. He was in emotional pain and had been for years—and he was sabotaging himself and his potential. It was time we did something about it.

    Self-Saboteur No More: How Treating Anxiety by Addressing SLC6A4, MTHFR, BDNF, CACNA1C, CD33, CHRHR1, and FUT2 Can Help Unleash your Full Potential

    You may remember our prior blog series, “Self-Saboteur,”, in which we talked about the various ways we can sabotage our lives. Sam was a self-saboteur of his very own neurobiology. In order to help Sam regain control and stop sabotaging his life, I wanted to discuss what triggered his decline. The first was his retirement from public life two years earlier, which had precipitated a life-stage crisis. Then two law school friends had passed away within weeks of each other. And Sam had also developed metabolic syndrome a year ago.  He was feeling all-too-mortal, and lacked meaning and purpose in his life. We would address his life-stage issues later, once we squared away his neurobiology. Sam’s prior medication trials hadn’t done much to attenuate his symptoms of anxiety, mild depression, and insomnia, including Clonazepam, Xanax, Ambien, and Lexapro.

    Our first step was to initiate a thorough diagnostic workup including blood studies, and Genomind’s Genecept and Mindful DNA Genetic Assays to determine his personal genome. The blood studies were quite revealing, including several elevated inflammatory biomarkers, and low levels of Vitamin D and B2. We placed him on a Mediterranean Diet and vitamin supplementation to address these issues.

    We then addressed his myriad genetic testing variants with the following epigenetic modifiers, in a stepwise fashion over 6 months:

    To treat his “risk” SLC6A4 S/S gene, which can predispose individuals to a depression that can be related to excessive serotonin activity in the amygdala, and area of the brain which is involved in mood regulation, anxiety states, and cognition (remember the “orchid” tale from last week?). Patients with this genotype have higher rates of lack of effectiveness and adverse events on SSRIs, and so we gave Sam Bupropion, a non-SSRI antidepressant that targets your body’s norepinephrine and dopamine levels rather than its serotonin levels.

    To address his “risk” MTHFR gene, which produced lower levels of an enzyme that plays a key role in producing the neurotransmitters crucial to maintaining our mental health, Sam began taking l-methylfolate supplements.

    Sam began a daily exercise regimen to stimulate the production of BDNF—the brain’s “fertilizer gene”—which in turn would help his brain increase its adaptability, plasticity, and functional potential.

    Sam’s CACNA1C gene was prone to “excitatory signaling” which meant high stress situations could be hard for him to manage while maintaining an even mood. To mitigate this, I prescribed Memantine and Nimodipine (which also treated his high blood pressure).

    We addressed a variant of his CD33 gene, which left him prone to possible neuronal damage, by placing Sam on a Melatonin CR supplementation (which also positively modifies CACNA1C expression).

    The finishing touches to Sam’s precision medicine regimen included taking N-acetylcysteine for his CHRHR1 gene, to reduce his “fight, flight or freeze” reactions,  and rotating probiotic strains for his FUT2 gene, which had left him prone to gastrointestinal issues.

    Own Your Fear through Genetic Testing and Treatment—And Stop Sabotaging Your Life!

    As we monitored Sam’s progress on his medications and lifestyle changes, we addressed his life-stage crisis in psychotherapy—and I hereby confess that I really looked forward to seeing him every week, where he would regale me with stories of international crisis management, high-level diplomacy, and his behind-the-scenes insights (the “real story”) into people I’d read about on the front page of the newspaper for the past three decades! And as he began to feel physically better, he was able to move from a purely supportive therapy to an insight-oriented one. After seven months in treatment, this formerly incapacitated “diplomatic rock star” began to reengage with life. And as a result, I believe the world will become a better place. He joined a think tank to help shape national policy regarding Russia, appeared from time-to-time on the evening news as a consultant, and had begun seeing a lovely woman. In our last session, as a show of gratitude, he brought me a vase filled with flowers (not orchids!) which was a delightful first! Together, we celebrated his “cure.


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