Genetic Testing, Nutrition and Psychotherapy in the Treatment of Bipolar Depression

Adele* was a young mother in her early thirties who had a master’s degree in engineering and who practiced patent law, was highly valued by her law firm, and presented with a long and complicated history, punctuated by frequent crying spells, living what she described as a “scripted life” that she felt was written for her and not by her, and feeling “out of sorts” in every area of her life. She came in to see me for a second opinion 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.

Several years before I began treating her she was diagnosed with post-partum depression following the birth of her daughter, Susan, and had suffered from chronic fatigue and depression that antedated the pregnancy. She had grown up in a household that had lacked emotional warmth, with a mother who was demanding, histrionic, and never satisfied with life or anyone around her; and an emotionally distant father. Her mother created in Adele a feeling of helplessness, as she could never predict when mother would erupt in tears or anger, or level her scathing criticisms toward Adele. Her mother had continued this type of behavior to this day, and 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.

In retrospect, following initial treatment with an SSRI antidepressant by an earlier doctor she had seen, she began to develop feelings that 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, impaired concentration and executive functioning, excessive spending, despair and feelings of hopelessness, and a variety of unusual sensory experiences.

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, which she described as “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 the patent law firm to attempt to regain her health. In addition, she 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. So Adele, despite her youthful age, 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 patent attorney, which is a highly respected profession; 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 feel confident that I can help you.”

The first 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) as we weaned her off the SSRI, then added Wellbutrin (an antidepressant that treats “frontal lobe” depression associated with low energy levels and cognitive impairment). She began to improve somewhat, but her cognitive functioning remained quite impaired, so we added Namenda (a really interesting medication that was first used to help slow the progression of Alzheimer’s Disease, and which has recently been shown to provide mood stabilization and improved cognitive functioning in patients with bipolar disorder).

Simultaneously we arranged for a neurology workup including 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, several vitamin deficiencies, elevated inflammatory biomarkers indicating generalized increased inflammation throughout her body, and a number of delayed hypersensitivity food allergies due to a leaky gut syndrome. An overnight polysomnogram (a test for sleep disorders) was negative for sleep apnea syndrome, and a Lyme Disease screening test was also negative. 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.

Working together in a partnership we began to pursue a number of paths in parallel to restore Adele’s health. We increased the Lamictal, Wellbutrin and Namenda, and added thyroid and vitamin supplementation. Over several months her symptoms improved approximately 50% on this regimen. During the following nine months of treatment a number of additional interventions were added: due to persisting daytime fatigue we added a low dose of Nuvigil, which also helped her focus and concentration; to address her food allergies, we placed her on an elimination diet of the most offending foods followed by a rotational diet, and rotated the less offending foods, based upon their lower level of immunoreactivity; and she also began working out with a personal trainer, and pursued an exercise program three days per week.

Slowly but surely 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. However, the current standard of care in our profession is to strive toward 100% remission – yet there was not much else I could think of to add or subtract to help her feel better. “Adele, we have made good progress together, and I am proud of how diligently you have been implementing this complicated regimen that we have devised to help you. Your motivation and determination are impressive.”

Around this time we were approached by a salesperson for a new genetic test for psychiatric patients – from Genomind – that assayed a panel of ten genes via simply taking a swab to the inside cheek area to procure cells to analyze – to determine a number of parameters of how a particular patient’s neurons (brain cells) might vary in function from the average person’s cells. Adele and I discussed this test and decided to pursue it as it could only provide us additional information to possibly help her. The results turned out to be most interesting, as she had several genetic variations that can affect mood regulation and cognitive functioning. To begin with, she lacked enough of an enzyme – Methylenetetrahydrafolate Reductase – that is part of a sequence of chemical reactions responsible for converting folic acid (a B vitamin) into L-methylfolate – which is a necessary factor for the manufacture of enough levels of dopamine, norepinephrine and serotonin in the brain. These three neurotransmitters are crucially involved in the regulation of mood, cognition, and energy levels. She also was shown to have a genetic variation associate with excessive levels of calcium channel activity in the brain – a channel which helps to determine the rate that a brain cell fires or depolarizes – whereby, in my experience, excessive levels of calcium channel activity can promote anxiety, fear, and panic along with a generalized state of excessive arousal that is draining and wearing on one’s spirit. The psychiatric research literature also documents that this genetic variant is associated with bipolar disorder and depression.

To treat these genetic variations we added L-methylfolate, and Magnesium Malate which blocks some of the calcium from entering the calcium channels. Since her genetic test findings are also associated with reduced mitochondrial energy production, we added Creatine 2 grams daily, which enhances energy production in the mitochondria.

Low and behold, after about a year of treatment, the effects of these stepwise and complex interventions, while not miraculous, restored Adele to over 90% return of her baseline functioning – such that she was able to return to work four days per week after having been out of work for over two years. This immense step of returning to the practice of patent law left Adele fraught with some anxiety for sure, yet served to give her self-esteem a huge boost. We both anticipate that she will return to full-time work in the coming months.

“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 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.

The lesson here is that a comprehensive treatment plan can address a number of the epigenetic stressors that perpetuate and worsen a patient’s mood disorder or anxiety. With Adele we reduced sources of inflammation, improved her nutritional status, restored normal levels of hormones and vitamins, helped her achieve more control over her life by enabling her to set effective limits on her mother and receive reasonable accommodations at work, and treated her mood disorder and genotype with a personalized combination of medication and supplements.

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