CHAPTER 8: G IS FOR GENETICS: KNOW YOUR VULNERABILITIES, BUT YOUR HISTORY IS NOT YOUR DESTINY

The individual nature of a single cell can be compared to that of a manuscript. Each cell inherits the same first draft. Over time, words are scratched out and others are added; genes are silenced or activated. Different qualities or phrases are emphasized; and a unique novel is born from an otherwise standard script. Humans derive their individuality from epigenomes, which are triggered by chance events, like injuries, smells, infections, or falling in love.

SIDDHARTHA MUKHERJEE, THE GENE: AN INTIMATE HISTORY

EMMY

Emmy, our nine-year-old granddaughter, started having intense seizures when she was just five months old. In one day, she had 160 of them. I was lecturing in Boston when my daughter texted me videos of the seizures where it looked as if Emmy was being electrocuted. Emmy was diagnosed with infantile spasms (later shown to be caused by a very rare genetic disorder, Koolen-de Vries Syndrome), which is associated with seizures, heart disease, and developmental delays. The neurologist gave us the grim news that Emmy might never walk and had a 30 percent chance of dying before the age of three. He wanted to put her on a medicine that was $26,000 a dose and loaded with side effects, including wiping out her immune system.

I asked about trying the ketogenic diet, which has been found to be helpful for many children with seizure disorders. Her doctor laughed at me and told me it didn’t have any science supporting its use. My wife, Tana, later told me she knew the relationship had gone sour when I asked the doctor if he knew how to read. “You’re kidding me,” I said. “It has more than 75 studies showing it decreases seizure frequency in children, with some children becoming seizure free. The studies were done at a little place in Baltimore called Johns Hopkins. You’ve heard of Johns Hopkins?” I was frustrated.

The doctor said if we wanted to try the ketogenic diet, he would not be Emmy’s doctor. “You’re fired,” I replied. “How did you get through medical school without learning about informed consent? You’re supposed to give us reasonable options, and we decide what to do, remember?”

I then called the ketogenic clinic at Oregon Health & Science University and talked to their director, who told us the diet was an option for Emmy. Within three months on the diet, her seizures subsided, and by age three, Emmy was walking to preschool.[295] It was through Emmy and many children like her I learned that although genes may increase your risk for brain health/mental health illness they can often be modified by smart, targeted interventions.

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Although genes may increase your vulnerability to brain health/mental health trouble, they can often be modified by smart, targeted interventions.

 

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If you have family members with brain health/mental health challenges, such as anxiety disorders, obsessive-compulsive disorder (OCD), depression, bipolar disorder, schizophrenia, addictions, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), Alzheimer’s disease, or Parkinson’s, you have a higher risk of having them too. Studies on identical twins and within families have shown the high genetic nature of many brain health/mental health issues.

FAMILIAL RISK OF PSYCHIATRIC ILLNESS[296]

Illness	Identical Twins	Siblings	General Population
Autism	69%	6%	0.6%
Schizophrenia	50%	9%	0.9%
Bipolar Disorder	40%	5%	1%
Depression	44%	20%	6%
Anxiety Disorder	40%	25%	6%
ADHD	66%	36%	5–15%

Yet having a genetic risk is not a death sentence; it should be a wake-up call for you to know your vulnerabilities and get serious about taking care of your brain. As you can see in the chart above, identical twins, who have identical genes, are just as likely not to develop the same conditions as their twin when it comes to schizophrenia, bipolar disorder, depression, and anxiety disorders. Genes load the gun; your behavior and environment pull the trigger.

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Genes load the gun; your behavior and environment pull the trigger.

 

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The Lincoln Legacy

Abraham Lincoln’s family tree is loaded with brain health/mental health issues. His mother, Nancy Lincoln, was described as sad, and his father often got the “blues” with strange spells where he wanted to be alone. His paternal great uncle told a court he had a “deranged mind.” His uncle Mordecai Lincoln had severe mood swings, which got worse with heavy drinking. Mordecai’s three sons struggled with depression, and one of them swung between depression and mania. One of Abraham Lincoln’s first cousins had a daughter, Mary Jane Lincoln, who was committed to the Illinois State Hospital for the Insane. During her trial, the jury concluded, “The disease is with her hereditary,” meaning that mental illness ran in her family.[297] It is clear that Abraham Lincoln suffered with periods of depression, even voicing suicidal thoughts. Yet, at the same time, in many ways, he was the epitome of mental health and was able to keep the United States together during its darkest days. His genes were not his destiny.

GENETICS AND THE FOUR CIRCLES

You may think that genetics are purely biological, but they can impact all four circles and, likewise, all four circles can influence your genes, as well as those of your children, grandchildren, and beyond —just as my nieces, Alizé and Amelie, were at risk because of their family history.

• Biological: Humans are made up of 23 pairs of chromosomes —one set from each parent —that are found in their DNA in the nuclei of their cells. All humans share 99.99 percent of their genetic code with other humans (so much for feeling special). We share about 98 percent with chimpanzees, about 60 percent with bananas, and about 33 percent with yeast. A gene is a very small part of a chromosome that codes for making different proteins, which in turn make up your cells and, ultimately, you. A lucky person has just the right number of chromosomes and genes. When the number of chromosomes is wrong, when there are extra or defective genes, or when there are certain gene variants, you become more susceptible to issues. For example, heart disease and obesity run in my family, but I do not have either because I don’t give in to the behaviors that make them more likely.

• Psychological: Too many people believe the false notion that they are condemned to have diabetes, obesity, hypertension, bipolar disorder, depression, or Alzheimer’s disease because of their genetic family history. This leads them to develop a defeatist attitude and bad habits that make it likely to be so.

• Social: Many people adopt their families’ unhealthy behaviors, which increases their risk of developing the brain/mental illnesses for which they have a genetic predisposition.

• Spiritual: If you don’t have a strong purpose in life, you are less likely to know why you want to turn off those genetic vulnerabilities.

HOW PSYCHIATRIC ISSUES IN YOUR FAMILY MAKE YOU MORE SUSCEPTIBLE TO TROUBLE

1. 1. You have the genetic vulnerability.

1. 2. You are more likely to have experienced lasting stress because of the psychiatric challenges in your family. For example, children who grow up with stress or abuse from a parent or relative are significantly more likely to experience lasting anxiety or depression.

1. 3. The stress of the illnesses in prior generations changed your genes to become more vulnerable to trouble. Stress, poor diets, environmental toxins, and prenatal nutrition in earlier generations actually changed their genes (epigenetics) to be more likely to express trouble.

1. 4. If your family members self-medicate with bad habits, you are likely to pick up those same behaviors, which increases your risk of brain health/mental health issues.

1. 5. If your family doesn’t care enough about their own health or about your well-being to change their behavior, it can be harder for you to learn to love yourself enough to adopt a healthier lifestyle.

The more of these factors you have, the higher your risk. Think of it this way: When my daughters, Breanne, Kaitlyn, and Chloe, and granddaughters, Emmy and Haven, were born, they were born with all of the eggs in their ovaries they will ever have. They were all influenced by their mother’s habits and my habits. In turn, their habits will turn on or off certain genes that will make illness more or less likely in them and, subsequently, in their babies and grandbabies. Similarly, my nieces, Alizé and Amelie, were born with genes that were influenced by the habits of their parents and grandparents. To end mental illness in Alizé and Amelie and their future children and grandchildren, they need to focus on brain health in an attempt to turn off any of those genes that increased their vulnerability to psychiatric issues.

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Genes are not a death sentence; they should be a wake-up call for you to know your risks and work hard to prevent them.

 

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YOUR ANXIETY MAY BE FROM ANOTHER TIME

In fascinating but disturbing research, fear has been shown to be passed down through generations. You may be afraid of something and have absolutely no idea why. Researchers Brian Dias and Kerry Ressler from Emory University made mice afraid of a cherry blossom scent by shocking them whenever the smell was in the air.[298] In scientific circles, this is called classical fear conditioning, and this result came as no surprise. What was startling, however, was the fact that the rodents’ offspring and even the following generation were also afraid of the scent of cherry blossoms, even though they were never exposed to the shocks. The fear was actually transmitted epigenetically.

The implications of this research are wide-reaching. Emotions like fear, anxiety, and perhaps even hatred may have ancestral origins. If you are afraid of something and have no idea why, go back through your genealogy and look for any clues that the fear may actually have nothing to do with your own experience. Prior-generation stress has also been associated with depression, antisocial behaviors, and memory impairment. Fortunately, it seems that stress in your ancestors can go both ways; another study suggested prior-generation stress can help animals learn to better cope with stress.[299]

GENETIC RISKS FOR BRAIN HEALTH ISSUES

• Family history of neurological illnesses
• Family history of psychiatric illnesses, including addictions
• Not being serious about health, despite family history
• Epigenetic factors, such as poor diet, environmental toxins, unresolved emotional trauma, and so on

Would it be any surprise how an evil or benevolent ruler would use your genetics against you or to help you?

GENETICS

THE EVIL RULER WOULD . . .

1. 1. Tell people who have a family history of brain health/mental health illnesses not to worry about taking care of their health because there is nothing they can do about it.
2. 2. Adopt “Live It Up While You Can” as the nation’s public health slogan.
3. 3. Tell subjects there’s no point in dealing with their emotional baggage because once they are dead, they are finished.

THE BENEVOLENT RULER WOULD . . .

1. 1. Inform the population that genes are not everything and learn from the misguided eugenics movement of the 19th and 20th centuries.
2. 2. Educate the population to know their genetic risks and vulnerabilities by having families tell accurate stories of their ancestors and be serious about prevention as soon as possible.
3. 3. Encourage people to be serious about healthy BRIGHT MINDS lifestyle habits and develop public service programs to let people know about epigenetics.
4. 4. Remind people that their behavior is not just about them; it is about generations of them.

SOME GUIDING GENETIC PRINCIPLES

1. 1. Genes do not cause illnesses. They make proteins, which have specific functions. The translation process from gene to functional protein is controlled and regulated by other genes and by the availability of nutrients that come from the diet.
2. 2. Few medical illnesses are caused by a malfunction of a single gene.
3. 3. Very rarely is any brain health/mental health disorder caused by a single gene. More often, multiple genes are involved.
4. 4. Even though we are born with all the genes we’ll ever have; their expression is influenced by all of the four circles (biological, psychological, social, and spiritual) and BRIGHT MINDS risk factors. This process is called epigenetics. It is rarely your genes by themselves that cause trouble. Nature and nurture always work together to create who we are and how we feel.
5. 5. Small genetic abnormalities are more common in those with autism, schizophrenia, bipolar disorder, and nicotine dependence than in healthy people.[300]
6. 6. Genetic testing is still in its infancy but will likely play an important role in the future of brain health/mental health. For now, genetic testing cannot give a brain health/mental health diagnosis, but it may give clues about vulnerabilities, which medications or supplements may help, and how you metabolize certain medications. For example, if you are of Asian ancestry and your doctor is considering the mood stabilizer carbamazepine (Tegretol), the genetic marker HLA-B*1502 should be tested because it substantially increases the risk of developing serious side effects.[301]

   Genetic testing is beyond the scope of this book, but I want to give you a sense of a few of the genes researchers believe may have some practical application to brain health. There is not a consensus about these findings among scientists, so be cautious in how you interpret this information.

   Some terminology can help:

   • Every person has two copies of each gene, one from their mother and one from their father.
   • Genotype is the array of genes an individual has.
   • A nonideal variant contains one or two copies of affected genes, also called alleles. Alleles are the variations of any one specific gene.
   • The genetic markers below are simply markers of genetic predisposition. Dietary, environmental, and epigenetic factors often modify the influence of these markers on a person’s health. Having a positive marker does not necessarily mean that an action needs to be taken.

PRESCRIPTIONS FOR REDUCING YOUR GENETIC RISK FACTORS
(AND THE FOUR CIRCLES THEY REPRESENT)

The Strategies

1. 1. Care about your genes and know your vulnerability. If you have genetic risk factors or a family history of brain health/mental health issues, get an early screening for the genes listed above. Genomind (www.genomind.com) and Genesight (www.genesight.com) are two companies our clinicians use at Amen Clinics. Questionnaires to screen for brain health/mental health issues, cognitive testing, and possibly brain SPECT imaging may be helpful.

1. 2. Avoid any risk factors that accelerate disease for your genetics (social circle if you do these activities with friends). Here’s an example: Any child who wants to play a contact sport with a likelihood of concussions (football, soccer, hockey, horseback riding, etc.) should be screened for the APOE e4 gene. Its presence increases the risk of cognitive decline and dementia later in life tenfold![302] If they have an APOE e4 gene, they should consider noncontact sports, such as golf, tennis, table tennis, cross-country running, track, and dance.

1. 3. Engage in regular healthy habits to decrease the expression of problem-promoting genes. Be serious about prevention as soon as possible and attack all 11 of the BRIGHT MINDS risk factors. If you have brain health/mental health issues in your family, you should want to be vigilant about brain health. It could make all the difference for you and your family. Studies have shown a lower risk of dementia in people with one or two of the APOE e4 genes if they had higher education levels and participated in leisure activities like sports or hobbies that involved new learning.[303] They also did better if their blood flow and vascular risk factors, such as hypertension, smoking, or heart problems, were low.

1. 4. Take nutraceuticals related to any genetic variants you may have. Refer to the chart in appendix B, and work with an integrative practitioner to determine your risks.

DO YOU WANT A BETTER BRAIN 11 YEARS FROM NOW?

One of my all-time favorite stories involves my friend Leeza Gibbons. Leeza has been a television personality for decades, having appeared as a correspondent and cohost of Entertainment Tonight for 16 years and then hosting her own daytime talk show, where we met. Her grandmother and mother died with Alzheimer’s disease, and she was terrified she would get it as well. During a stressful time, she came to one of our clinics when she was 51, and her scan was not healthy, which, given her family history, was very concerning. But Leeza didn’t allow the news to depress her; rather, it motivated her to follow the strategies in this book to enhance her brain. When I scanned her 11 years later, it was remarkably better. You are not stuck with the brain you have; you can make it better, even 11 years later.

Leeza and Dr. Amen

LEEZA AND DR. AMEN

Leeza, Age 51 SPECT Scan

Low blood flow to areas vulnerable to Alzheimer’s

Age 62

Improved overall

BRIGHT MINDS: GENETICS

STEPS TO CREATE MENTAL ILLNESS . . . AND MAKE MY NIECES, ALIZÉ AND AMELIE, SUFFER

1. 1. Believe your genes are your destiny.
2. 2. Engage in habits that turn on genetic vulnerabilities.
   • Adopt your family’s poor eating habits.
   • Self-medicate with substances like alcohol, cigarettes, and sugar.
   • Ignore stress management techniques.
   • Don’t deal with the emotional trauma from living with family members with psychiatric illness.
   • Don’t seek to understand how your genetics may make you more vulnerable to brain health/mental health issues.
   • Think that your behaviors affect no one but yourself.
3. 3. Avoid the strategies that turn off genetic vulnerabilities.

STEPS TO END MENTAL ILLNESS . . . AND KEEP MY NIECES, ALIZÉ AND AMELIE, HEALTHY

1. 1. Believe your behavior can turn on or turn off the genes that increase your vulnerability for brain health/mental health issues.
2. 2. Avoid anything that turns on genetic vulnerabilities.
3. 3. Engage regularly in healthy habits that turn off genetic vulnerabilities.
   • Consume a BRIGHT MINDS diet.
   • Address all your BRIGHT MINDS risk factors to deal with any brain health/mental health issues.
   • Practice prayer, meditation, or other ways to cope with stress.
   • Work on addressing past emotional trauma so you do not have to spread it to future generations. If you already did, help those generations get help.
   • Consider genetic testing to identify any vulnerabilities.
   • Remember that your behavior is not just about you; it’s about generations of you.

Pick One BRIGHT MINDS Genetics Tiny Habit to Start Today

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1. If there are brain health/mental health issues in my family, I will consider early screening.
2. If there is a family history of psychiatric problems in my family, I will remember that my behavior and environment can turn on or off the genes that increase my chances for brain/mental illness.
3. When I suspect I may have a brain health/mental health issue, I will consider testing my genetic vulnerabilities.
4. If I have the APO E4 gene, I will avoid contact sports and other head trauma risks.
5. When I make lifestyle choices, I will remember that my choices affect not only me, but also my children, my grandchildren, and future generations.

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[295] Daniel G. Amen and Tana Amen, The Brain Warrior’s Way (New York: New American Library, 2016), 31.

[296] Rosaline J. Neuman et al., “Latent Class Analysis of ADHD and Comorbid Symptoms in a Population Sample of Adolescent Female Twins,” Journal of Child Psychology and Psychiatry 42, no. 7 (October 2001): 933–42.

Cori Bargmann, “Overview of Genes and Behavior,” YouTube, November 1, 2013, www.youtube.com/watch?v=4qhrnOP8euI&feature=youtu.be.

[297] Joshua Wolf Shenk, Lincoln’s Melancholy (New York: Houghton Mifflin, 2005), 80.

[298] Brian G. Dias and Kerry J. Ressler, “Parental Olfactory Experience Influences Behavior and Neural Structure in Subsequent Generations,” Nature Neuroscience 17, no. 1 (2014): 89–96.

[299] Katharina Gapp et al., “Early Life Stress in Fathers Improves Behavioural Flexibility in Their Offspring,” Nature Communications 5, no. 5466 (2014).

[300] Michael J. Gandal et al., “Shared Molecular Neuropathology across Major Psychiatric Disorders Parallels Polygenic Overlap,” Science 359, no. 6376 (February 9, 2018)): 693–97, doi: 10.1126/science.aad6469.

D. B. Hancock et al., “Genome-Wide Association Study across European and African American Ancestries Identifies a SNP in DNMT3B Contributing to Nicotine Dependence,” Molecular Psychiatry 23, no. 9 (September 2018): 1911–19.

[301] U. Amstutz et al., “Recommendations for HLA-B*15:02 and HLA-A*31:01 Genetic Testing to Reduce the Risk of Carbamazepine-Induced Hypersensitivity Reactions,” Epilepsia 55, no. 4 (April 2014): 496–506. doi: 10.1111/epi.12564.

[302] M. X. Tang et al., “Effect of Age, Ethnicity, and Head Injury on the Association between APOE Genotypes and Alzheimer’s Disease,” Annals of New York Academy of Sciences 802 (December 16, 1996): 6–15.

[303] S. T. Cheng, “Cognitive Reserve and the Prevention of Dementia: The Role of Physical and Cognitive Activities,” Current Psychiatry Reports 18, no. 9 (September 2016): 85, doi:10.1007/s11920-016-0721-2.