Hardwiring the Brain: Epigenetic Modification in a Case of Childhood Rage

 In Pediatrics

Nicole Cain, ND, MA

Tolle Causam

As many as 1,080,168 children in the United States, ages 0-5, are taking a psychiatric drug.1 If we expand the age range to 0-17, that number jumps up drastically to 8,389,034. The primary types of medications prescribed for children include amphetamines, antidepressants, antipsychotics, and benzodiazepines.1

Each category of medication has its own side-effect profile, which is, in part, responsible for the high attrition rate seen in children and young adults with psychiatric concerns. In addition to the issues of poor drug compliance and undesirable side effects, there are deleterious long-term consequences associated with pharmacological treatment alone.

The purpose of this article is to discuss an actual case of a child with a behavioral disorder who was treated with pharmacological treatments that had various consequences. Specifically, it will address the unique approach taken by naturopathic physicians in terms of their evaluation, conceptualization, and approach to complex cases, as well as relevant treatments that follow the naturopathic Therapeutic Order.

The Naturopathic Therapeutic Order

  1. Address acute concerns
  2. Remove obstacles to cure / Treat the root cause
  3. Give the body what it needs
  4. Stimulate the body’s innate ability to heal
  5. Tonify weak and damaged systems
  6. Correct structural integrity
  7. Address the pathology
  8. Suppress the pathology

Case Study: Max

Max, a 10-year-old male, presented to my office in 2014. He had been diagnosed with Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder Type I (rapid cycling, mixed depression and anxiety), and Conduct Disorder. His family was affluent, educated, and eager to find a resolution to their son’s suffering.

Max’s symptoms included episodic rage alternating with panic attacks and impulsivity. He engaged in self-harm behaviors, including cutting, striking his head against the wall, and scratching. He had uncontrollable outbursts in which he would cause destruction to his own property and sometimes lash out and attack his mother. Afterward, he felt incredible remorse and would cycle into self-flagellation where he would deprive himself of food and water. He also experienced severe migraine headaches, sleeping difficulties, frequent ear infections, poor memory, jaw pain, poor appetite, gas, bloating, and foul odor of his stool, joint pains, and muscle aches. Developmentally, he was very emotionally sensitive, and he struggled academically and cognitively. He was Tanner Stage I, but was tall for his age as compared to his cohort.

Max’s medical team was comprised of a primary-care pediatrician, neurologist, psychiatrist, and psychotherapist. He had been granted an individualized education plan and a program coordinator through his school. His parents had also received counseling in order to rule out any sort of family dynamics, inside or outside of the home, that might be contributing to their child’s behavior.

Treatments had consisted of individual and family counseling, supplements, and pharmacological management. The patient’s parents reported that Max had taken dozens of medications but that each had caused a worsening of symptoms. At presentation, Max had been prescribed the following drugs:

  • Oxcarbazepine: 600 mg BID
  • Venlafaxine: 37.5 mg Q 3 days
  • Lamotrigine: 50 mg in AM, 200 mg in PM
  • Guanfacine: 2 mg QD

Max’s parents shared that they had consulted medical doctors, osteopaths, acupuncturists, chiropractors, and “Functional Medicine” experts. In addition to his pharmacy of prescription pills, Max had been given vitamins, herbs, Chinese herbs, amino acids, enzymes, probiotics, and countless other nutrients. He had completed dietary trials of gluten-free, dairy-free, egg-free, and whatever-else-free eating. He had done Candida cleanses, as well as testing for fructose malabsorption and celiac disease. They had in-home programming, counseling, behavioral coaching, and more.

For all intents and purposes, they had tried almost everything. But Max was not getting any better and the family wanted to know why.

The trio sat across from me and waited as I reviewed the stack of food allergy tests, neurotransmitter tests, stool analyses, and other records that they had saved throughout the years of seeking answers.

Genetics as Root Cause?

A key factor that differentiates naturopathic doctors from other types of clinicians is the tenet of identifying and treating the root cause. Not addressing the cause can become an obstacle to cure. The lack of efficacy in Max’s treatment tells us that we are missing something.

Following all of his symptoms downstream and searching for a uniting origin, I was led to examine his genetic material. Using a reputable company, I did genetic testing on Max and the results were beyond extraordinary.

Before discussing Max’s results, it is helpful to have a basic understanding of genetics. Compound heterozygote refers to when an organism has 2 recessive forms of a gene that arise by mutation at a particular gene location. An allele is usually 1 of 2 forms of a gene that has undergone 1 or more mutations. For example, both chromosomal alleles might be mutated but the locations may vary. A mutation affecting only 1 allele/form of genes is called heterozygous. A chromosome is hemizygous when only 1 copy is present. Hemizygosity is also observed when 1 copy of a gene is deleted, or in the heterogametic sex when a gene is located on a sex chromosome.

People typically have 2 sex chromosomes in each cell: females have 2 X chromosomes (46,XX), and males have 1 X and 1 Y chromosome (46,XY).

Genetic Testing Results

Max’s results show that he had 2 X chromosomes on many of his genes. Follow-up microarray testing further elucidated that Max had 2 X chromosomes and a Y chromosome on a large number of his genes. The associated syndrome is Klinefelter syndrome. Most often, Klinefelter syndrome results from the presence of 1 extra copy of the X chromosome in each cell (47,XXY).

Klinefelter syndrome is associated with a myriad of possible symptoms, but predominantly includes intense anger, rage, and violence towards oneself or others. When I read through the list of symptoms and traits, it was as if I was reading a description of Klinefelter syndrome, when I was actually reading Max’s case history.

Additionally, we found a mutation at the HK3 gene, which is responsible for encoding hexokinase 3. This gene is associated with pain and is a likely contributor to Max’s myriad pain complaints.

He also had a mutation at SLC6A8, which is a gene that encodes creatine transport, ie, helping cells carry creatine across the blood-brain barrier into the brain. Issues in creatine transport can result in many psychiatric issues, as well as issues with muscle power and neurological function.

Lastly, Max had a COX3 mutation. Cytochrome C Oxidase (COX) subunit III are units of DNA involved with respiratory complex IV. Complex IV is located in the mitochondria (the power plants in each cell of your body) and is involved in the electron transport chain of oxidative phosphorylation. Oxidative phosphorylation helps the body transfer oxygen in the process of making energy so that the body can transport protons into the mitochondria. Similar to the engine of your car, if the mitochondria are not properly tuned, lots of oxidative damage, or “exhaust,” is produced. This destroys cells all over the brain and body and can result in psychiatric concerns, pain issues, and more.2

While medical testing cannot yet tell us how the genes are behaving (eg, epigenetics), we can correlate our genetic testing results with the expression of the body. Through examining Max’s symptoms, with consideration of his genetic material, we can generate hypotheses about the origin of his symptoms and devise treatments to treat that genetic mutation. If the treatment results in symptom improvement, we have modified the genetic expression, thus treating the cause instead of palliating the symptoms through continued use of multiple medications.


Our treatment plan for Max consisted of the following:

  1. We evaluated the family’s acute needs and recommended further genetic counseling. Counselors can be found at nsgc.org. We also created a working relationship with his entire treatment team.
  2. Remove obstacles to cure. Because Max’s medications were ineffective at assisting him and seemed to only make his symptoms worse, we worked with his psychiatrist to begin tapering him off his medications.
  3. Give the body what it needs. The following supplements were prescribed:
    a) Creatine Powder: 5 g (or one 4-g scoop) TID. This addresses the SLC6A8 mutation by providing the body with increased amounts of creatine to increase bioavailability for those genes that are functioning in the role of transport.
    b) Ubiquinone COQ10: 200 mg (1 cap) in AM. This oxidized form of COQ10 offers powerful antioxidant support to address the COX3 and HK3 gene mutations.
    c) Ubiquinol COQ10: 100 mg (1 cap) TID (AM, lunch, PM). This reduced form of CoQ10 offers additional powerful antioxidant support to address the COX3 and HK3 gene mutations.
    d) Liposomal Glutathione (containing 250 mg glutathione and 125 mg phospholipid complex per capsule): 1 cap in AM. In 2 weeks, increase to 1 cap in AM and 1 cap in PM. This offers powerful antioxidant support to address the COX3 and HK3 gene mutations.
    e) Alpha Lipoic Acid: 600 mg (1 cap) QD with food. This offers powerful antioxidant support to address the COX3 and HK3 gene mutations.
  4. Stimulate the body’s ability to heal itself. By understanding the common symptoms associated with the diagnoses revealed through genetic testing, I was better able to identify the most “characteristic symptoms” in Max’s case. A new homeopathic remedy was prescribed and we administered a single dose of 2 pellets PO.
  5. Max also started to do physical therapy for his various body pains.

One-Month Follow-up

Follow-up 1 month later revealed the following improvements:

  • Anger outbursts: Max had, on average, 1 major outburst per week during the last 4 weeks. This major outburst lasted 1 hour, and the intensity was 8/10 (10 being the worst). There were a few smaller outbursts that lasted about 30 minutes, with an intensity of 3-4/10.
    • Previously: Frequency: 6 times per day. Duration: 30 minutes to 3 hours. Intensity: 8-10/10.
  • Anxiety attacks: Max had 1 anxiety attack when dropped off at school on a field-trip day. He was able to recover from this anxiety attack, however. Beforehand, he would become so triggered that he’d miss the outing. However, this time Max was able to collect himself after about 20 minutes and he enjoyed the outing. He has had minor anxiety on a daily basis, but it has not gone above a 3/10.
    • Previously: Frequency: 3 times per day. Duration: 30 minutes to 2 hours. Intensity: 6-10/10 depending on triggers (eg, going outside, leaving home, school).
  • Remorse, or Violence toward self: He has not scratched himself. He only hit his head once, which was during a major outburst.
    • Previously: Frequency: 3 times per day, especially in the late afternoons. Duration: intermittent and explosive, happening in short bursts that last under 5 minutes. Intensity: 6/10 (with 10 as the worst intensity of violence in the behavior).
  • Violence toward others: Max attacked his mom during the major outburst. Otherwise, he is doing more “annoying” behaviors, such as poking, tickling, pestering the family dog, and singing loudly.
    • Previously: Screaming, biting, scratching, punching, kicking behaviors. Frequency: these coincide with the anger outbursts, about 6 times per day. Duration: 30 minutes to 3 hours. Intensity: 8-10/10.
  • Neck pain: In the visit, Max reports that his neck still hurts “a lot,” but his mom states that he has not mentioned it in the last 2 weeks, whereas before he would bring it up multiple times per day. He also seems to have increased active range of motion.
    • Previously: Frequency: daily. Duration: Complained about it throughout the day. Intensity: difficult to assess; patient stated, “It’s the worst pain of my life!”
  • Muscle aches: Max denies any muscle pains at the visit. Mom says they’ve wondered if the muscle pains were a medication side effect.
    • Previously: Frequency: daily, worse at bedtime or a nap. Duration: all day. Intensity: difficult to assess; similar to neck pain.
  • Joint pains: Max reports that his knees hurt after recess, during which he plays soccer outside. Mom reports that Max does not complain about knee pain at bedtime or after a nap any longer.
    • Previously: Frequency: daily, worst at bedtime or a nap. Duration: all day. Intensity: difficult to assess; similar to neck pain.
  • Tapering medications: Going well; no negative sequel observed.

Overall: Max and his parents are thrilled with his progress. They continue to utilize the behavioral coaching and counseling, and Max is now taking the supplements recommended, based on his genetic testing. We agreed that since he appeared to be continuing to improve, we did not need to re-dose his homeopathic treatment.

Two-Year Follow-up & Summary

We followed up monthly, and Max’s progress followed a pattern of 2 steps forward and 1 step backward. Periodic adjustments to his protocol had to be made, based on his symptomatic presentation. After 2 years of treatment, Max made a remarkable transformation. He had discontinued all of his medications, and felt healthier in his body. His body pains had ultimately resolved, and he was enjoying stable relationships with other kids his age. There was greater peace in the home, and a sense of accomplishment and respect among the treatment team.

The body has an incredible ability to heal itself. If you have not found success in the treatment of your loved one, or if you are a clinician and you have hit a roadblock with a patient, it is likely that a vital piece of information is missing.

By digging deeper, identifying the root cause of symptoms and treating it gives the body space to do what it does best: heal. Max had seen fabulous doctors, who endeavored to identify the root cause. But as it turned out, Max’s genetic material required that his case be managed with very specific and unique treatments. It was only through following the Therapeutic Order, in all of its brilliance, did Max enjoy the freedom to experience true healing.

While it is very likely that Max will require life-long treatment due to Klinefelter Syndrome, he is empowered with the knowledge of what additional support his body needs. Armed with that knowledge, he now has relief from a vast majority of his symptoms and can proceed to live a life of wonderment.


  1. Citizens Commission on Human Rights International. Number of Children & Adolescents Taking Psychiatric Drugs in the U.S. April 2014. CCHR Web site. https://www.cchrint.org/psychiatric-drugs/children-on-psychiatric-drugs/. Accessed April 15, 2017.
  2. Genetics Home Reference. Klinefelter syndrome. U.S. National Library of Medicine. Reviewed January 2013. GHR Web site. https://ghr.nlm.nih.gov/condition/klinefelter-syndrome#genes. Accessed April 15, 2017.
Image Copyright: <a href=’https://www.123rf.com/profile_tatyanagl’>tatyanagl / 123RF Stock Photo</a>

Nicole Cain, ND, MA, is an expert in the field of integrative treatments for mental health. She is the only naturopathic doctor in the United States with an additional degree in Clinical Psychology and expertise in mental health, including homeopathic approaches to bipolar disorder. Dr Cain is the founder of Natural Mental Health Supplements, has taught clinical and didactic psychology at the Southwest Naturopathic Medical Center. She has 2 private practice locations: Scottsdale, AZ, and Grand Rapids, MI. She sees patients in the United States and internationally. When not hard at work, Dr Cain enjoys doing macramé, spending time with her husband, and “treasure hunting” at antique shops.

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