Breakthrough Theory of Bipolar Disorder

This past week, I had the pleasure of attending the Advanced Course for Walsh-Trained Practitioners. To date, 1,200 practitioners from 75 countries have been trained using the Walsh approach.For those unfamiliar, the Walsh Research Institute, founded by Dr. William Walsh, has looked at the nutrient levels of over 30,000 people with brain-related symptoms and found a surprisingly small number of nutrient imbalances (low zinc, high copper, high pyrroles, and methylation imbalances) that repeatedly show up. We address these imbalances in those with depression, anxiety, panic, obsessions, compulsions, inattention, brain fog, hyperactivity, autism, dementia, psychosis, and mood swings with significant and, at times, dramatic results. Bipolar disorder, however, because of its shifting in neurotransmitter states from mania and depression, can be particularly difficult to treat. More than nine million Americans have been diagnosed with bipolar disorder. This severe condition can lead to drug or alcohol use, financial or legal problems, discord in relationships, work and school instability, and/or suicide attempts or suicide. The course typically begins with an acute onset, followed by episodes of mania and depression, which often worsens in severity over time.In this post, after describing bipolar disorder, I will use Dr. Walsh’s Comprehensive Theory of Bipolar Disorder, recently shared at the Society of Neuroscience, to explain:* the cause of bipolar disorder* the reason for the onset, persistence, and increasing severity for many over time* the reason for the increased risk of other health issues* the reason for the switch between manic and depressive states* how this information impacts treatment and preventionBipolar DisorderIt is important to note that the type of bipolar disorder I am referring to here is Bipolar I, a condition in which there are discrete episodes of mania often followed by episodes of depression. Such episodes can occur rarely or even multiple times a year.Manic episodes usually last a week up to several months and include three or more of the following:* increase in activity, energy, or agitation* distorted sense of well-being or self-confidence* needing much less sleep than usual* usually talkative or talking fast* racing thoughts or flight of ideas (jumping from one topic to another)* easily distracted* poor decision-making- e.g., excessive spending, risky sexual behavior* may become psychotic (have a break from reality)Hypomania has less severe symptoms which have less impact on functioning at work, school, social activities, and relationships. Having hypomanic episodes is not sufficient to warrant a diagnosis of Bipolar I.Depressive episodes, which often last a couple of weeks but can vary, include five or more of the below symptoms that are affecting functioning at work, school, social activities, and relationships:* depressed mood (sad, lacking feeling, hopeless, irritable, angry, or tearful)* marked loss of interest or enjoyment of activities* weight loss or weight gain (without dieting or overeating)* too much or too little sleep* behavior slowed down or restless* fatigue - loss of energy* feelings of worthlessness or inappropriate guilt* problems concentrating or making decisions* suicidal thoughts, plans, or attemptsBipolar II Disorder is a different condition. This diagnosis is given when someone has at least one major depressive episode and at least one hypomanic episode. Depressive episodes are often longer here. There is never a manic episode. Despite its name, this is not a milder form of Bipolar I. Biochemically, it is considered a different disorder.Rapid cycling is used to describe bipolar disorder when, in the past year, there have been at least four episodes of switching from mania or hypomania to depression. This can describe either type I or type II (depending on the presence or absence of mania). As with many other diagnoses, the terms came from seemingly related symptoms instead of a root cause or biochemical understanding.Dr. Walsh’s comprehensive theory, which I’ll describe, focuses on Bipolar I, in which there are manic episodes usually followed by depressive episodes. For those who struggle with mood swings changing within a day or a week as opposed to discrete mood episodes of mania or depression, pyrrole disorder should be considered.Genetics or Epigenetics?Having a first-degree relative (parent or sibling) with bipolar disorder raises the risk of developing bipolar disorder. After thirty years of genetic research, however, a gene for bipolar disorder has not been identified. The genetics are more complicated. It appears there are many genes involved.2021 Genome-Wide Association Study (GWAS)These studies compared the genomes of about 5,000 individuals with bipolar disorder and about 8,000 (controls/individuals without bipolar disorder). Over time, more and more “bipolar” genetic variants have been identified. By 2021, there were 64; however, there are expected to be hundreds. Of these 64 genetic variants, 49 are DNA repair genes and antioxidant genes that occur throughout the body (not just the brain). Just as it sounds, DNA repair genes make enzymes that repair DNA. Antioxidant genes make enzymes that support our protective antioxidant systems. Many of these genetic variants are also associated with cancer and other conditions impacted by DNA damage. This would suggest that those with bipolar disorder come into the world with a vulnerability in their ability to repair DNA damage (which translates to cell damage, tissue damage, and, in the case of the brain, neuronal damage. An event, however, is required to shift this vulnerability to illness.Accelerated DNA DamageWhat damages DNA? Free radicals and thus oxidative stress. To remind you, oxidative stress occurs when our body’s inherent antioxidant systems are overwhelmed or depleted by free radicals (due to an insult - a toxic exposure(s), source of inflammation, or trauma). A depletion of our protection leaves our cells and DNA vulnerable to further oxidative stress and damage. If we have variants on protective genes, then we can be even more vulnerable.Numerous studies have found high levels of superoxide, hydroxyl, and ONNO (peroxynitrite)free radicals in those with bipolar disorder.This vulnerability to DNA damage also explains why many with bipolar disorder have a higher risk of other health issues, including heart disease, breast cancer, multiple sclerosis, kidney failure, immune disorders, migraines, gastrointestinal illnesses, and others. But What About the Other 15 Genes? Genetic Weakness on Ion ChannelsThe remaining identified genes are more specific to bipolar disorder and relate to ion channel genes. Ion channels exist on the neuronal membranes, allowing potassium, sodium, and calcium to move in and out of the nerve cell. This movement creates an electrical charge that travels down the cell, releasing a neurotransmitter into the space between that neuron and other neurons to communicate with the next cell(s). OnsetHere again, an epigenetic event (toxic exposure, trauma, significant illness, etc.) leading to oxidative overload impacts the production of the proteins used in these channels, which affects the movement of ions in and out of the cell (more specifically causing flooding of potassium ions (K+) outside the cell) leading to hyperactivity of that nerve. This is why Dr. Walsh’s theory considers bipolar disorder a channelopathy.EuthymiaEuthymia - when the mood is neither manic nor depressed - interestingly, appears to be the first mood state after the onset of the condition. The flooding of K+ outside the cell leads to hyperactivity of neurons for serotonin. However, that doesn’t appear to cause symptoms since serotonin inhibits or keeps the activity of dopamine, norepinephrine, and glutamate in check.ManiaThe onset of mania starts to occur when the serotonin neuron hyperactivity (from the K+ flooding outside the cells) starts to fizzle out. What follows is a reduction in the inhibition of the neurotransmitters (dopamine, norepinephrine, glutamate, and others) that cause widespread neuronal hyperactivity, which causes manic symptoms.Eventually, the declining serotonin activity becomes the dominating force and triggers depression, which may persist for some time. Eventually, the serotonin nerves return to hyperactivity (again keeping things at bay), resulting in a stable mood - euthymia. Progression of Illness It is well known that preventing manic episodes can prevent the severity of the condition from escalating over time. Dr. Walsh’s theory also addresses why.Aside from impacting neurotransmission, the problems occurring at the ion channels are also associated with further DNA damage. This means that each episode can potentially add to the DNA damage. Add to this typical DNA damage (for all of us) that comes with aging. A typically untreated original and often persistent insult (such as a toxic exposure), events occurring at the ion channel, and aging can lead to the progression and increasing severity of illness.TreatmentAs with any theory, the inevitable question becomes, how does this impact treatment? Allopathic or mainstream psychiatry uses medication approaches that aim and usually succeed at stabilizing mood. Again, this is important because of the consequences of mania or depression but also because of the potential physiologic damage caused by ongoing episodes. What isn’t typically addressed in conventional psychiatry are:* Sources of oxidative stress. Does this person have mold toxicity, Lyme, metal toxicity, candida or other microbial overgrowth, chemical exposures, high EMF exposure, trauma, and/or chronic stress that are continuing to deplete protections and contribute to DNA damage? These are the types of issues that those of us who consider ourselves functional and environmental psychiatrists address.* Support for the antioxidant system. As with any brain condition, robust antioxidant support is indicated to address free radicals, but in this case, it is also indicated to prevent further DNA damage and to protect the ion channels. * Nutrient imbalances in varying combinations are typically also involved, such as methylation imbalances (often overmethylation), pyrrole disorder, and copper-zinc imbalances. Each of these can be exacerbated by high oxidative stress, which is a further cause of oxidative stress.Research into targeted antioxidants will be needed to build upon Dr. Walsh’s research. The free radicals (superoxide, hydroxyl ions, and ONNO) are more easily addressed in the body than in the brain. In the meantime, in addition to more typical antioxidants, NAC (which inhibits activity at the glutamate receptor) and MT (metallothionein) promotion therapy (a combination of glutathione, zinc, B6, and specific amino acids) are expected to be beneficial.PreventionBecause bipolar disorder appears to be an epigenetic DNA damage illness (caused by major oxidative overload), early antioxidant treatment in those who are vulnerable to bipolar disorder may prevent the onset and development of this disease. It won’t be long before such vulnerabilities can be identified, as early as infancy.For more on the work of Dr. William Walsh and the Walsh Research Institute Practioner Resource Map (, visit: https://www.walshinstitute.org/As always, I welcome your comments and questions.And if you would like to help me get this information out into the world, please consider sharing.Until next time,Courtney P.S. To learn more about non-patient consultations, treatment, and monthly mentorship groups, please visit my website at:CourtneySnyderMD.comMedical Disclaimer:This newsletter is for educational purposes and not intended or implied to be a substitute for professional medical advice, diagnosis, or treatment for yourself or others, including but not limited to patients you are treating (if you are a practitioner). Consult your physician for any medical issues that you may be having. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit courtneysnydermd.substack.com/subscribe