• Gavin Guard, Medical Director

The many faces of mental health: what causes mood imbalances and what to do about it

Updated: 7 days ago

Key Takeaways

  • Mental health disorders have a genetic component but also have many biological causes

  • Many of these causes are treatable with a functional medicine approach


*in this article, I refer to mood “disorders”. By no means, is this meant to be demeaning or degrading. Rather, my hope is that this term sheds light on the notion of a disorganized brain function that is leading to these symptoms. *


Intro

Mental health is turning out to be a hot topic these days. That is because 1 in 5 people have anxiety and 1 in 10 have diagnosed depression. These numbers are probably even greater if we account for the people suffering from these conditions who go undiagnosed.

As science grows, so does our understanding of these disorders. Once thought to be just a genetic issue, mood imbalances have a strong biological component. This is good news! Instead of just chalking up these conditions to “poor genetics” or all in the person’s head, we now know that there are many underlying causes to mental health disorders.

In this article, I will uncover the many causes of mental health and mood imbalances. By addressing these factors, you can heal your brain and get back to a happier, healthier life.


Learn how probiotics can help with anxiety and depression


A broken brain

Our brain does not have any pain receptors. This means, the symptoms from a broken brain manifest much differently than other organs. If we have joint disease, we have joint pain. If we have a gut issue, we often have abdominal discomfort. The brain is different though. Often, inflammation and dysfunction in the brain present as less obvious symptoms.


Poor cognition, brain fog, fatigue, chronic pain, and mood imbalances are all signs of a broken brain that needs to be addressed.

However, a proper assessment of brain function and the underlying factors that affect it often go inadequately addressed in a conventional 15-20 minute doctor visit.

Let’s examine what is needed for a healthy brain and what are the main causes of mood imbalances and mental health disorders.


Work with me to help heal your brain


Genetics

I would be remised if I did not talk about genetics. Our genes absolutely impact if we do or do not develop mental health illness.

Many genes have been associated with bipolar disorder, depression, and anxiety. These genes impact how we neurotransmitter production/metabolism, neuron function, stress hormone signaling, and size/volume of specific brain regions.


Nonetheless, in twin studies, heritability for something like bipolar disorder is anywhere from 40-70%. This means that if an identical twin has bipolar, there is a 40-70% chance the other twin will have it.


This points to the fact that genes are important but are not decisive.

A term called “epigenetics” refers to the overall environmental exposure that we have that impacts our gene expression. This means that our genes are not our destiny and our environment- the food we eat, the air we breathe, our sleep/exercise/work patterns, etc.- all act as information that tells our body to either turn certain genes on or off. One paper stated that “epigenetic changes reflecting an alteration of gene expression influenced by life events may play a significant role in different phases of bipolar illness.”


This is empowering as it points to the fact that you are not confined to your genes alone. Your genetics are the hand of cards you were dealt, but how you play your hand matters most.

Poor glucose control and oxygen delivery

It’s important to realize that our brain is made up of cells. Specifically, it’s made up of neurons and glial cells (support cells). When these cells become dysfunctional (for whatever reason), the neural tissue (e.g. nerves) that is comprised of these cells become dysfunctional. When the neural tissue becomes dysfunctional, the brain and spinal cord tracts that are made up of the neural tissue becomes dysfunctional.


You can see then, that a state of dysfunctional cells will eventually lead to a dysfunctional brain and nervous system.

With this in mind, we need to understand what makes a cell healthy. A neuron needs 3 basic things to be healthy:

1. Glucose (sugar)

2. Oxygen

3. Stimulation

All 3 of these factors are important, but the first two are often an unnoticed issue for patients with mood imbalances and mental health disorders.

Proper glucose control (not too high or not too low) is vital for proper neuron function, and thus, brain function. However, just a fasting glucose and A1C measurements (which are typically the only thing looked at on a conventional blood sugar panel) are just the tip of the iceberg when considering the body’s glucose regulation. These markers do not account for blood sugar spikes after a meal or how hard the body is fighting to keep glucose under control. That is why I will also order C-peptide/insulin levels as well as a marker called “Glycomark” to get a better understanding of how the body is handling blood sugar.

Oxygen deliverability is another important aspect of neuron health. Anemia is characterized by poor oxygen deliverability to tissues. While most people think of iron-deficiency anemia, there are many causes of anemia including folate and B12 deficiency, low thyroid, B6/copper/zinc deficiency, kidney disease, liver disease, and chronic inflammation. All of these factors need to be looked at and addressed in order to get oxygen to your brain to function optimally.


Inflammation

Many drugs used for depression, anxiety, and bipolar disorders are targeted at lowering or increasing specific neurotransmitters. You have probably heard of SSRIs (e.g. Zoloft, Prozac) which are designed to increase serotonin in the synapses between neurons. There is a big debate currently arguing against this reductionistic view of mood imbalances. Many researchers are pointing to a more validated hypothesis of mood disorders called the “cytokine theory”.


The cytokine theory hypothesizes that many mental health disorders are caused or at least perpetuated, by chronic inflammation.

Increased inflammation has been associated with fatigue, loss of interest, impairment of concentration, anxiety, irritability, body aches, and disturbances in sleep and appetite.

Many studies have found increased levels of pro-inflammatory biomarkers in the blood of participants with mood imbalances. For example, higher levels of C-reactive protein (a protein that is increased during inflammation) was elevated during manic episodes as well as in depressed groups of people. These findings have been replicated in at least 5 meta-analysis (a review of other multiple studies).


Learn how probiotics can reduce inflammation

To further demonstrate this point, one paper noted that when those with hepatitis C were given a pro-inflammatory drug (IFN-gamma) to treat their hepatitis, a large number of patients developed manic symptoms.

A drug called lithium is a front-line therapy for mood stabilization. It has been shown to have anti-inflammatory effects.


Also, literature supports the use of low-dose aspirin in the management of mood disorders such as depression.

Let’s look at some processes that can cause chronic inflammation

  • Poor diet

  • Gut issues

  • Viral, bacterial, parasitic infection

  • Chronic stress

  • Sleep deprivation

  • Anemia

  • Toxic burden

  • Autoimmunity

It is thought that inflammation is the beginning of the cascade the onset of many mental health disorders. This may be because neuroinflammation (inflammation in the brain) can impact neurotransmitter production/metabolism/receptor activity as well as damage neurons directly. Inflammation can also reduce the volume of the hippocampus, which is the memory-forming part of the brain.

It’s been observed that those with mental health disorders have a lower life expectancy that cannot be attributed to increased suicide rates alone. Rather, higher rates of inflammatory conditions such as cardiovascular disease diabetes in those with mental health disorders are a key example of the inflammation-mental health link.

What’s even more alarming is that inflammation elsewhere in our body can cause inflammation in the brain.


Therefore, problems like joint degeneration, gut issues, and chronic sinus infections can cause an inflamed brain.

Autoimmunity

There is some great research pointing to an autoimmune component to many mental health disorders. One paper noted that there were 30 different autoimmune diseases that were a risk factor for the onset of bipolar disorder. While it’s hard to discern whether this is correlation (is autoimmunity just associated with bipolar?) versus correlation (is autoimmunity perhaps a core process in the onset of bipolar?), there is some evidence pointing to the latter (causation). To illustrate this, researchers noted that autoimmune disease such as Crohn’s disease, autoimmune hepatitis, and Guillain-Barre syndrome occur before the onset of bipolar. Given that inflammation and autoimmunity go hand-in-hand, this points us back to the notion that inflammation plays a large role in the onset of mood imbalances.

Learn how probiotics can help with autoimmunity


Those who have had past concussion have higher rates of mental health illnesses. After a concussion, the blood brain barrier opens up and can allow for influx of immune cells in the brain that then tag the brain tissue for destruction.


This process of autoimmunity after a concussion may a be a key driver of the association between concussions and mental health disorders.


Mitochondria dysfunction

You may have remembered from your high school biology class that mitochondria are the powerhouse of the cell. Mitochondria are the small “kidney bean- shaped” organelles in our cells that provide energy. However, they also play a role in hemoglobin production, fighting off infections, regulating inflammation, promoting stem cells, and killing the dysfunctional cells. Our neurons are very dense in mitochondria. It’s no surprise then, that dysfunction of these mitochondria has been associated in many mental health and neurological disorders.


When our mitochondria are not working properly, they produce oxidative damage and inflammation. Both oxidative damage and inflammation lead to further mitochondrial dysfunction, creating a vicious loop. Increased levels of oxidative stress have been associated with depression and bipolar disorder.


Research has provided evidence that there are less mitochondria, different shapes of mitochondria, and mitochondrial DNA mutations in those with bipolar. Biopsies of bipolar patients’ brains after their death have confirmed impairments of mitochondrial energy production, increased cell death caused by mitochondrial dysfunction, and increased oxidative stress.

Furthermore, the prevalence of bipolar disorder in mitochondrial diseases is about 20%, which is nearly 20 times higher than the general population. Interestingly, lithium, a drug commonly used as a mood stabilizer, has been shown to improve the health of the mitochondria.

One paper noted that 35% of all medications cause mitochondria dysfunction. This includes medications such as metformin, ibuprofen, statins, antibiotics, and antiviral drugs. What’s even more alarming is that the drugs used for mood disorders (anti-depressants, anti-psychotics) are also potent inhibitors of mitochondrial function.

I’m not saying that drugs are bad, in many cases they are needed. However, a thorough medication evaluation is necessary to see why you may be experiencing symptoms of a broken brain.

Fortunately, there are many things you can do to recover the health of your mitochondria. Such interventions include:

  • Caloric restriction

  • Time-restricted feeding

  • A proper detox program (many programs are worthless, and some can make toxic burden even worse)

  • Treat an underlying infection

  • Addressing psychological stress

  • Regulating blood sugar

  • Pruning dysfunctional mitochondria and promoting healthy mitochondria with specific compounds

The bottom line

In this article, we uncovered the multi-faceted conundrum of mental health illness. Genetics play a role but are only a small part of the many factors that can lead to mood imbalances, irritability, anxiety, depression, mania, and sleep disturbances.


It’s empowering to understand that that there are evidence-based biological causes to mental illness. More importantly, it’s vital to know that you can do something about it.

Work with me to help heal your brain


I hope you found this information useful and helpful in your journey back to a healthier and happier life.

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Resources Cited

1. Dykens JA, Will Y. The significance of mitochondrial toxicity testing in drug development. Drug Discov Today. 2007;12(17-18):777-785. doi:10.1016/j.drudis.2007.07.013

2. Kato T. Neurobiological basis of bipolar disorder: Mitochondrial dysfunction hypothesis and beyond. Schizophr Res. 2017;187:62-66. doi:10.1016/j.schres.2016.10.037

3. Koopman WJ, Willems PH, Smeitink JA. Monogenic mitochondrial disorders. N Engl J Med. 2012;366(12):1132-1141. doi:10.1056/NEJMra1012478

4. Maletic V, Raison C. Integrated neurobiology of bipolar disorder. Front Psychiatry. 2014;5:98. Published 2014 Aug 25. doi:10.3389/fpsyt.2014.00098

5. Muneer A. Bipolar Disorder: Role of Inflammation and the Development of Disease Biomarkers. Psychiatry Investig. 2016;13(1):18-33. doi:10.4306/pi.2016.13.1.18

6. Sigitova E, Fišar Z, Hroudová J, Cikánková T, Raboch J. Biological hypotheses and biomarkers of bipolar disorder. Psychiatry Clin Neurosci. 2017;71(2):77-103. doi:10.1111/pcn.12476

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Gavin Guard, MPAS, PA-C, CISSN

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