Precision Psychiatry and Your Gene-Based Roadmap to Better Health

Becoming Whole

Every single one of us deserves to live a healthy, whole life. In fact, it is our birthright. The goal of therapy is to help patients access that wholeness to Become Whole —and that can take time, investment, and patience. It may also require getting a second opinion including genetic testing. To illustrate these principles, let’s embark upon a journey into the therapeutic process of one of our patients, a woman named Adele.* After months of psychotherapy and medication, she wasn’t getting better. But instead of giving up, she went deeper. Adele’s story is one of perseverance, personalized precision psychiatry—and one that we hope will encourage you to stick with therapy until you become whole, too.

A “Withered Orchid” Named Adele
by Dr. Bruce Kehr

Adele* was a young mother in her early thirties with a brilliant mind and promising career. She held a master’s degree in engineering as well as a law degree, and was highly valued as a patent lawyer at her law firm. Like so many of my patients, to the outside world she seemed to have it all. Yet when she came to see me, she told me in no uncertain terms she was actively considering ending her life. She had been

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referred to me for a second opinion by her primary care doctor, as she was not feeling or functioning well on the medication regimen prescribed by her current psychiatrist. She was also in weekly psychotherapy with a psychoanalytically-oriented psychotherapist but felt too impaired to use the therapy effectively. In other words, she was stuck—and dangerously so.

At our first session, Adele described through her tears a long and complicated history. However, an overarching theme began to emerge: She felt she was living a “scripted life,” one that was written for her but not by her. Nothing in her life felt right. “Dr. Kehr,” she said tearfully, “I am just not sure I want to go on living. I have no hope for ever recovering. I just feel so vulnerable all the time. I feel terribly sick, yet medications only seem to make me worse. I am at the end of the line.”

I didn’t know it yet, but Adele would turn out to be what I think of as a highly complex “Orchid.” You might remember from my prior blog post on the topic that a variant on your SLC6A4 gene may have a bearing on your levels of resilience: some gene variants allow individuals to persevere through challenges with relative ease—while other gene variants can make these same challenges more difficult to overcome. The knowledge and insight of one’s genetic makeup, paired with the personalized precision care that genetic testing facilitates, can have a major impact on “Orchid” types like Adele.

Several years before I began treating her, Adele was diagnosed with postpartum depression following the birth of her daughter, Susan. But her history with depression had begun well before that. Adele grew up in a household that had lacked emotional warmth. Her mother was demanding, histrionic, and never satisfied with life or anyone around her; her father was emotionally distant. Her mother created in Adele a feeling of helplessness, as she could never predict when her mother would erupt in tears or anger, or level scathing criticisms toward her. This type of toxic behavior didn’t end in childhood—in fact, it persisted in her mother as Adele and I began our work together. Adele never felt emotionally safe or comfortable around her. To complicate matters further, Adele had been repeatedly sexually abused between the ages of six and nine by her father. There couldn’t have been a worse childhood environment for this “Orchid.”

Adele had been on medication for a significant period of time—but a major factor of her feeling at her wit’s end was that her prescription didn’t seem to be helping. In fact, it seemed to make things worse. Following initial treatment with an SSRI antidepressant by an earlier doctor she had seen, she began to feel she was increasingly out of control of her emotions. She developed racing thoughts, increased anxiety, and sleeplessness which at the time were attributed to her being a new mother. However the symptoms began to worsen and included irritability, anger outbursts, frequent migraine headaches, impaired concentration and executive functioning, excessive spending, despair and feelings of hopelessness, and a variety of unusual sensory experiences. Suffice it to say, her daily life could be characterized as an extremely painful “roller coaster ride.”

While Adele had been in psychotherapy for the past several years to work through her having been sexually abused as a child, and the therapy was proceeding well according to her and her therapist, Adele began to experience what she described as episodes where she felt disconnected from others around her—including her baby daughter. She described these episodes as her “spells.” Her condition had further deteriorated to the point where she was unable to work, and she arranged for a prolonged medical leave of absence from her law firm to attempt to regain her health. To complicate things further, Adele had gained a substantial amount of weight as a result of the pregnancy—60 pounds—and had only been able to lose 20 of those pounds in the two years since she gave birth to Susan. Despite her youthful age, Adele presented with many of the symptoms of an unhealthy 80 year old, for in addition to her unstable mood disorder and gazing spells, she suffered from weight gain, gastrointestinal complaints, nausea, muscle and joint aches and pains, deficits in attention and recent memory function, fatigue, and a pervasive inability to concentrate.

At the end of our first session I said to her, “Adele, your story is a sad one, yet it is also filled with hope. Despite growing up with two disturbed parents, and being subjected by them to horrible emotional and sexual abuse, you survived your childhood, and your courage, intellect and drive helped you to become a highly respected attorney; and your capacity to love others, which is remarkable given the circumstances of your childhood, has enabled you to create a beautiful family with a loving husband and a lovely baby girl. Your medical situation is a complicated one, and it would appear that the antidepressant you are taking is worsening your underlying condition. We will begin to modify the underlying biological processes going on in your brain to help you feel better and function more effectively. I am confident I can help you—and I’m proud of you for not giving up.”

Step One: Genetic Testing – A Gene-by-Gene Roadmap to Better Health

To provide her a personalized precision psychiatric approach, we performed Genomind’s Professional PGx and Mental Health Map Assays through two simple cheek swabs. The results uncovered genetic variants in Adele’s SLC6A4, CACNA1C, COMT, MTHFR, BDNF, ABCA7, CD33, CHRNA5/3, FTO, LRP1, PPARG, FKBP5, HLADQB1, and CRP Genes. Armed with this information, we embarked on a thoughtful, persistent, progressive approach to restore her health.

Step Two: Diminishing the Devastation of Adele’s “Roller Coaster Ride Gene”

The next step was to stabilize her unstable mood disorder, which was complicated by her extreme sensitivity to medications; and to determine whether her sensory illusions and “spells” resulted from childhood sexual abuse (perhaps a type of dissociation) or temporal lobe seizures. She initially responded to low doses of Lamictal (an antidepressant and mood stabilizer that downregulates the effects of CACNA1C gene expression) as we weaned her off the SSRI. You may recall from my prior blog on CACNA1C that variants on this particular gene play a role in the way our bodies regulate our emotions. Some variants make it much harder for us to “come down” from an emotional high, and leave us stuck on that emotional roller coaster ride for far longer than we’d like. She began to improve somewhat, but her moods remained unstable. We then added another calcium channel blocker, Nimodipine, which provided further stabilization.

Adele’s cognitive functioning remained quite impaired, so we added Namenda (this calcium channel blocker is a fascinating medication: it was first used to help slow the progression of Alzheimer’s Disease and has recently been shown to provide mood stabilization and improved cognitive functioning in patients with bipolar disorder as well). Namenda began to help further stabilize her mood and improve her anxiety levels while also improving her cognitive functioning.

Step Three: Systematically Solving Adele’s “Neurotransmitter Manufacturing Gene”, “Dopamine and Norepinephrine Depleting Gene”, and “Brain Fertilizer and Resilience Gene”

When individuals are treated for mood disorders, the underlying problem often lies with three key neurotransmitters: serotonin, norepinephrine, and dopamine. The abundance of these chemicals in the body are absolutely critical in mood and anxiety symptom improvement. And they also happen to be regulated by the MTHFR gene. In my prior blog, I dubbed the MTHFR gene the “manufacturing gene”, and for good reason: depending on your gene variant, your body will naturally produce more of these neurotransmitters—or less. Adele’s body was producing less. Adele’s low levels of dopamine and norepinephrine were also caused by a Val/Val variant on her COMT gene. To help her body naturally produce more of those crucial chemicals, we began her on Methylfolate.

BDNF is another gene crucial to the production of critical neurotransmitters—I call it the “fertilizer gene.” The BDNF gene promotes the survival and growth of brain cells and connective synapses, and helps your body to produce those critical neurotransmitters that stabilize your mood. Adele’s brain’s resilience to stress was impaired by her BDNF gene variant, so we added L-theanine to boost these important neurotransmitters further, and improve the resilience of her brain cells and synaptic connections. Modafinil further increased her frontal lobe cognitive functioning by increasing dopamine and norepinephrine levels.

Step Four: Addressing Adele’s “Brain Health Genes” to Build Her a Healthier Brain

Adele’s other genetic variations placed her at higher risk for dementia, elevated stress response, migraine headaches, metabolic syndrome (obesity, type 2 diabetes, high blood pressure, elevated cholesterol), and celiac/gluten sensitivity, narcolepsy, and systemic chronic inflammation and autoimmunity. This may sound like quite a lot, but the important thing to keep in mind is that lifestyle modifications and prescription medication when needed can target every single one of these issues—and genetic testing is what allows for the level of specificity and precision that produces results over time.

We arranged for a neurology workup including a sleep study, a 48 hour EEG, which revealed some focal cortical irritability in the left temporal lobe; and extensive blood work, which revealed low levels of thyroid hormone, insulin resistance, excess cholesterol, several vitamin deficiencies, elevated inflammatory biomarkers indicating generalized increased inflammation throughout her body, and gluten sensitivity. It was obvious from these test results that there were a number of epigenetic factors that were negatively affecting her mood and thinking, and so we developed a stepwise interventional strategy to address each of them that involved a gluten-free Mediterranean Diet, thyroid hormone replacement, Vitamin supplements, rotation of three different probiotics, and Curcumin to reduce inflammation. She also began working out with a personal trainer and pursued an exercise program three days per week.

Two Years Later: Adele Became Whole Once Again

After we established a treatment plan based on Adele’s individual genetic roadmap, I checked in with her at three-month intervals to ensure the plan was going well. Steadily over time, this regimen began to improve her mood, outlook, cognitive functioning, and energy level. By the end of the first year she had improved about 80% and felt hopeful for the first time in several years. Her psychotherapy was going better as she now had enough energy to face the intensely painful feelings and memories associated with having been abused. She learned how to set effective limits on her mother, improve her relationship with her husband, and find a lower-stress legal job, all of which helped this lovely orchid woman begin to grow and thrive once again! Low and behold, after about two years of treatment, the effects of these stepwise and complex interventions, while not miraculous, restored Adele to over 90% return of her baseline functioning.

“Adele, we have made tremendous progress working together. I am so happy for you. You are finally at the point where you can work far more effectively in your talk therapy, to hopefully resolve once and for all the abuse you sustained as a child; and through returning to work in a more nurturing work culture you can begin to restore your professional identity, one for which you worked so hard for so many years. Hopefully your success as a wife, mother and attorney; along with the strong bond you have with your psychotherapist; will enable you to finally resolve the conflicts that you have carried inside of you for so long.” She wept tears of joy, and I thanked her for being so diligent in working with me in a true partnership on this long and winding road to recovery.

Personalized Precision Psychiatry

While Genetic testing is no “Magic Bullet,” the lesson here is that through a personalized, precise, and persistent treatment plan; guided by one’s personal genetic variations; a number of the epigenetic stressors that perpetuate and worsen a patient’s mood disorder or anxiety can be systematically addressed and corrected.

Adele, who once felt hopelessly ill, had her hope and health restored. Reader, if you stick with treatment and work with your doctor to understand your underlying genetics, there is hope for you, too. Don’t give up!

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We’ll aim to contact you by telephone within one business day to speak with you about our services and how we can help you or your loved one.

Wherever possible we will arrange to see you for your initial appointment within two business days of our first telephone call with you.

Please call (301) 984-9791 Monday-Friday between 9:00am and 5:00pm to request an appointment by telephone.

*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.