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    Oxidative Stress and Mental Health: Treat Brain Cell HAZMAT through Genetic Testing

    “I’m to eliminate free radicals, Moneypenny.”

    ―James Bond, "Never Say Never Again"

    What You Will Learn in this Blog:

    • How mood and anxiety disorders result in accelerated cellular aging
    • The aging process is caused by inflammation and oxidative stress which produce free radicals
    • How free radicals damage mitochondria, our cellular “power plants”
    • Certain genes, uncovered through genetic testing, increase one’s vulnerability to free radicals and inflammation, and increase mitochondrial damage
    • How to “turn off” damaging genes, and “turn on” reparative genes to reduce inflammation, quench free radicals, and improve cellular health and mental wellness

    My Dear Reader: I fervently hope that you have continued to dodge the COVID bullet, and that for you and your loved ones, life is returning to some semblance of normalcy. That said, after nearly two years of drastic changes in your life, there may be some things that remain stubbornly abnormal—and perhaps seemingly out of your control. 

    For instance, if you are like nearly half of all Americans, you may have gained weight during the pandemic. If this sounds familiar, you likely know this level of weight gain can lead to real psychological distress, harming both your body image and your overall sense of self. But a sense of unwellness is far from the only consequence of gaining significant weight: the systemic inflammation that accompanies weight gain creates increased oxidative stress, which in turn accelerates the aging process in both our bodies and our brains… and it just so happens that accelerated cellular aging is one of the hallmarks of serious mood and anxiety disorders. 

    In an earlier blog about “fire in your brain” we discussed the damaging effects of this kind of inflammation, which results in “inflammaging.” Today we will describe how inflammation results from the formation of “free radicals” and how these free radicals produce oxidative stress that worsens depression by affecting the millions of proteins, enzymes, and mitochondria that reside inside each of the 30 trillion human cells and 200 billion brain cells in our bodies. Systemic inflammation and oxidative stress can lead to serious health problems. But there are steps you can take to reverse their effects. This blog will explain how. 

    Inflammation and Oxidative Stress Can Lead to an Earlier Death

    Even when suicide is excluded, individuals with serious mental disorders die at an earlier average age due to increased risk of developing chronic illnesses such as heart disease, stroke, type 2 diabetes, immune system problems in the brain and elsewhere (called “immunosenescence”), and Alzheimer’s Disease.

    There are many reasons for this, including genetic predisposition, biological changes set in motion by “macro-traumas,” and lifestyle factors which we have termed “micro-traumas.” To solve this problem, we need a paradigm shift in how we understand and treat mental illness, thinking of it more as a whole‐body, multi‐system illness rather than an illness rooted specifically in the brain alone. 

    By understanding the causes of such accelerated aging and death in all of our human cells, and what we can do about it, we can transform psychiatric care by transforming how our cells function together and separately. Let me explain how that’s possible.

    How do Inflammation and Oxidative Stress Cause Mental Illness and Early Aging? 

    Inflammation and oxidative stress damage our genes — our very DNA itself — through what is known as telomere shortening. Telomeres reside at the end of our chromosomes, and they protect and stabilize the DNA. Think of the DNA like a shoelace, and the telomeres are the little caps at the ends that protect the lace from unraveling. Telomere shortening can occur in response to inflammation, oxidative stress, stress hormones, and other factors, and is found in many chronic mental illnesses, the most common being mood disorders, anxiety, chronic stress, and schizophrenia. Because telomere shortening results in unstable genes, it can cause other chronic illnesses as well. 

    Inflammation and oxidative stress can also damage our mitochondria, which produce the energy inside our cells that powers life itself. We can think of mitochondria like nuclear power plants in our bodies: they run incredibly cleanly and efficiently in generating enormous power for their tiny size, yet they also generate “hazardous waste” that must be disposed of—waste that is known as “oxidative stressors.” 

    When affected by chronic stress and its “fight, flight or freeze” adrenal hormones, our mitochondria can contribute to the cellular aging process. Damage to these power plants can cause inefficient energy production and create even more inflammation and oxidative stressors in our bodies. It can quickly become a vicious cycle: indeed, mitochondrial dysfunction is associated with a wide range of psychiatric disorders. Dysfunction and poor energy production have been noted as a key player in depression, autism and dementia, bipolar disorder, and schizophrenia.  

    Inflammation and oxidative stress also damage other critical elements inside our cells, including amino acids, proteins, enzymes, cell walls, and other structures inside the cells, rendering our cells “senseless” and then “senescent” by damaging the information system that creates and maintains their very identities. 

    Genetic Testing, Mitochondrial Damage, and Mental Health

    There are a number of treatable genetic variants associated with both higher rates of psychiatric disorders and an increased risk of mitochondrial dysfunction. These variants can be tested using Genomind’s Professional PGx test, as well as its direct-to-consumer Mental Health Map. Below are a few of these disorders and their relationship to our genes, inflammation, and oxidative stress.   

    • Bipolar Disorder: Recent research has demonstrated that in patients with bipolar disorder, oxidative stress, mitochondrial function, and BDNF—our brain’s fertilizer gene—may influence each other, with lower levels of BDNF being associated with oxidative stress damage, resulting in damaged mitochondrial DNA. BDNF is reduced when we are subjected to chronic stress—all the more if we have the Val/Met variant. However, we can rapidly increase BDNF levels with daily exercise, high levels of omega 3s, a ketogenic diet, and microdose lithium.
    • Autism: A variant of the CRHR1 gene results in higher and more prolonged activation of the hormones leading to the fight-flight-or freeze response, which in turn elevates oxidative stress and mitochondrial damage, and breaks down the blood-brain barrier, resulting in brain inflammation. Several studies have reported mitochondrial dysfunction in autism.  Given that autism has also been associated with brain inflammation and oxidative stress, addressing these issues could have a significant benefit in children with Autism Spectrum Disorders.
    • Other mood disorders: The CACNA1C gene has been identified as one of the strongest genetic risk factors for mood disorders, including major depression and bipolar disorder. In the brain, this gene plays a pivotal role in turning on and turning off other genes, helping to grow new connections between brain cells to help new learning, and helping to keep brain cells alive. In earlier blogs we discussed how to reduce this gene’s expression (turning it “off”) to reduce anxiety, mood swings, and depression. Recent findings show that reducing this gene’s expression also protected against oxidative stress in mitochondria.

    Brain Nutrition and Supplements to Treat Oxidative Stress

    At this point you may be wondering: What can I do to fight off these negative stressors in my own body? Luckily, there are more than a few promising answers to that question.

    Antioxidants and other supplements help protect against inflammatory damage and oxidative stress, and there are numerous sources you can draw from, including the following

    • Polyphenols found in plants can increase expression of BDNF, and diets that are rich in these molecules have been shown to produce increased cognitive abilities, mood improvement, and lowered probability of neurodegenerative disorders like Alzheimer’s. 
    • Curcumin has anti-inflammatory and antioxidant effects along with antiviral, antifungal, and clearing amyloid proteins (considered a major factor in Alzheimer’s Disease). It normalizes concentration of serotonin and dopamine, important neurotransmitters that play a role in many mental disorders. 
    • EGCG represents a main component of green tea. Frequent green tea drinking can lower probability of depression occurrence and has potential to decrease symptoms of depression and stress and also increases cognitive abilities in consumers. 
    • An antidepressant-like effect was also confirmed in Ginkgo biloba by affecting serotonin and dopamine concentrations. Combined therapy with antidepressants and ginkgo biloba extract increases sleep efficacy and reduces awakenings. 
    • A polyphenol extracted from pine bark, Pycnogenol, improves symptoms of ADHD, normalizes level of neurotransmitters, and decreases oxidative stress. 
    • Coenzyme Q10 (CoQ10) represents an important antioxidant with anti-inflammatory and neuroprotective properties. Lowered level of CoQ10 is associated with mitochondrion dysfunction. Patients with drug resistant depression show lowered concentration of CoQ10 in comparison to healthy controls.
    • Omega 3 polyunsaturated fatty acids can be found in seafood and olive oil in high concentrations. Patients with depression, chronic fatigue, and bipolar disorder have been observed to have significantly decreased levels of omega 3s in comparison to healthy controls. Combined therapy of SSRI antidepressants with omegas is more effective than antidepressants alone. Consumption of at least one serving of fish a week also decreases cognitive decline in old age by approximately 10–13%. 
    • N-Acetyl cysteine (NAC) has been shown to possess anti-inflammatory properties. Administration of NAC to patients with depression as part of bipolar disorder causes significant decrease of depression severity and improves antidepressants effectiveness.
    • Deficiency of magnesium causes mild inflammation. Its shortage can cause symptoms of depression especially in elderly people. Greater intake of magnesium was associated with antidepressant-like effect in patients with depression. 
    • Lowered levels of selenium can be responsible for depressive mood, anxiety, and decline of cognitive function. Dietary intake of selenium can lower probability of postpartum depression and decrease depression severity. On the other hand, very high selenium status (110 μg/L) is also associated with depression. 
    • Deficiency of zinc is also associated with depression. Zinc stimulates BDNF expression and helps improve mood and cognition. 

    Additionally, some vitamin deficiencies are significant in creating greater oxidative stress. Significantly decreased level of vitamin E was found in depressed patients. A diet rich in Vitamin E also increases concentration of glutathione, a very powerful antioxidant. In patients with depression, lowered concentration of Vitamin C was also observed. Depression is also associated with shortage of folate and vitamin B12 levels.

    Reduce Oxidative Stress and Take Back your Health!

    Reader, while James Bond was unable to rid the world of free radicals, you can be an effective secret agent to rid them from your brain. Through understanding your personal genome, and taking gene-based supplements to reduce oxidative stress, you can rid these “terrorists” from your brain cells once and for all!

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