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Depression: Have You Considered These Causes?

Updated: Jun 5, 2023

sad girl slumped in window

There was a time when every day was a struggle to get out of bed. I’d cry for hours or lay there in a helpless daze. I couldn’t find joy in any of the activities that would normally make me happy.

I had experienced no emotional trauma or abuse. Yes, my parents had recently split up, and I was under a lot of stress, but was that the only cause? My blood tests were “normal.” According to my doctor, I was simply stressed and biochemically imbalanced. Prozac was the answer.

SSRIs (Selective serotonin reuptake inhibitors) like Fluoxetine (Prozac), Citalopram (Celexa) and Sertraline (Zoloft) are commonly prescribed for those suffering from depression. Along with counselling or psychotherapy, they’re the standard interventions in the medical world.

Like many antidepressant medications, SSRIs have many undesirable side effects, but of special note is the black box warning to younger users that it may increase suicidal thoughts! (1)

The exact mechanism of action for SSRIs is not fully understood, but it was theorized that low levels of the neurotransmitter serotonin were a major cause of depression. The drug prevented reuptake, and since serotonin was a key neurotransmitter involved in mood control, sleep and pain tolerance, increasing levels was meant to be the answer. Studies now dispute their effectiveness, with nearly 2 out of 3 patients with depression not achieving remission with either SSRIs or SNRIs (serotonin-norepinephrine reuptake inhibitor) monotherapy. (2)

Imbalanced levels of serotonin, both high and low, have been found to be associated with depression. Furthermore, serotonin is not the only neurotransmitter where imbalances have links to depression. Dopamine, norepinephrine, epinephrine, glutamate and GABA levels are just as important.

Neurotransmitters are chemical messengers that regulate many physical and emotional processes, including movement, cognition, stress response, emotions, energy, cravings, pain and more. They are nerve system messengers that facilitate communication between the brain, glands, organs and muscles.

nerve synapse and neurotransmitters

Also communicating vital messages are hormones. Released from endocrine glands into the bloodstream, hormones regulate the body's growth, metabolism (the physical and chemical processes of the body) and sexual development and functions.

The thyroid hormones, T3 and T4, are good examples. Released by the thyroid when stimulated by Thyroid Stimulating Hormone (TSH) from the pituitary gland, they impact every cell in the body! They play vital roles in metabolic, cardiovascular, reproductive and brain health.

Both decreased and increased concentrations of thyroid hormones lead to alterations in mental state. Too little thyroid hormone can lead to depressive symptoms, while too much can induce anxiety and nervousness.

Our mental well-being is very much reliant on the careful balance of these hormones and neurotransmitters.

Once one system is affected, it can impact all other systems of the body. It’s never a stand-alone problem, yet the standard approach looks downstream. Serotonin levels low? Give 5-HTP or SSRIs. Hypothyroid? Give levothyroxine. However, we need to consider the whole body. We need to ask, why are they low? Are other systems involved?

Although addressing the issue downstream may provide short-term relief, often the underlying cause is never addressed, and additional health concerns emerge in the future.

So, other than emotional trauma and abuse, what can be at the root of depression and many other mental health issues?

Well, the production and careful balance of the body’s hormones and neurotransmitters are reliant on several things…

1. The adequate supply of nutrients, antioxidants and enzymes

2. Low levels of chronic inflammation and oxidative stress

3. Our genetic makeup

4. Our gut health

5. Our stress levels

The adequate supply of nutrients, antioxidants and enzymes

For many biochemical reactions to take place in the body and for neurotransmitters and hormones to be synthesized, the body must have access to a wide range of nutrients.

Amino acids, the building blocks of protein, are essential for neurotransmitter synthesis. Most amino acids must be provided through our diet as they cannot be produced in the body. Serotonin, for example, is synthesized from the amino acid tryptophan with the help of the enzyme tryptophan hydroxylase. Sources of tryptophan include salmon, eggs, poultry, spinach, nuts and seeds.

healthy foods for the brain

Deficiencies in nutrients such as zinc and vitamin B6 (Pyridoxal-5-Phosphate or P5P) can alter brain levels of the neurotransmitter’s GABA, dopamine and norepinephrine, leading to a myriad of problems.

Low levels of P5P are associated with ADHD, muscle weakness, depression, anxiety and sleep disorders!

The mineral zinc has many important roles in brain function, and deficiencies are associated with delayed growth, temper problems, poor immune function, epilepsy, autism, hormone imbalances, neurodegenerative disorders and learning difficulties.

Low zinc levels can also lead to low P5P levels. For numerous vital chemical reactions to take place in the body, dietary vitamin B6 needs to be converted to its active form of P5P. It does this with the help of zinc!

Also, of note is folate or vitamin B9.

Approximately one third of depressed individuals are thought to have an outright folate deficiency. (3)

Most dietary folate requires the addition of a methyl group to become active: L-methylfolate or 5MTHF. The body makes this conversion with the help of vitamin B2 and an enzyme called MTHF-Reductase. An estimated 40% of the population struggles to convert dietary folate to its active form due to a gene mutation affecting the MTHFR enzyme. So even if dietary folate is adequate, sufficient levels of active folate can be difficult to reach.

Up to 70% of patients with depression test positive for the MTHFR gene mutation and supplementation with L-methylfolate has been suggested for the treatment of depression in several psychiatric journals. Folic acid, on the other hand, is not recommended as the conversion to active folate is even more challenging for the body than dietary folate. (4)

Folate, zinc and P5P are not the only nutrients involved in hormone regulation, neurotransmitter synthesis or with links to poor mental health. Vitamin D, vitamin C, iron, magnesium, choline, essential fatty acids (omega 3 and 6), vitamin B12 and other B vitamins may also play a role.

Important minerals for optimal thyroid function include iodine, selenium, iron and zinc.

So why are deficiencies so common? Because even if your diet is filled with a large selection of fruit and vegetables, healthy fats and protein, the nutrient content of our food supply has diminished. Medications like oral contraceptives and proton pump inhibitors for reflux (eg. omeprazole or losec) are also known to deplete essential nutrients. Then there are these four additional factors.

Inflammation, oxidative stress and cell damage

Anything that increases inflammation and free radicals in the body can have a negative impact by depleting essential nutrients and antioxidants or by destroying cells and impairing biochemical processes.

Environmental toxins, especially when combined with a poor ability to detoxify, are a recipe for disaster.

environmental toxins and pollution on a tongue

Heavy metal exposure from things like amalgam fillings, smoking, pollutants, surgical hardware, vaccines, contaminated fish and lead paints deplete essential nutrients like zinc, use up powerful antioxidants like glutathione and lead to inflammation, cell and tissue damage. Heavy metals also have an affinity for organs like the brain.

Solvents, pesticides, plasticisers, BPA, phthalates, parabens, electromagnetic radiation, mycotoxins from mould, food sensitivities, food chemicals and additives can also lead to inflammation, oxidative stress and cell damage.

Endotoxins from bacterial, viral, yeast or fungal infections are additional stressors. In some cases, their toxic metabolites can cause nerve damage and even have a direct effect on neurotransmitter function.

For example, the nasty hospital-acquired bacterial infection Clostridium difficile is known for its association with many mental health disorders, including depression, autism, ADHD, obsessive compulsive disorder, tourettes and even schizophrenia.

Our genetic makeup

The toxins have even more of an impact when we have “dirty genes.” Genetic SNPs (snips) can have an impact on our ability to detoxify, protect our cells and turn dangerous metabolites into inert ones.

Our genetic makeup loads the gun, but lifestyle pulls the trigger.

Dr Mark Hyman

I’ve already mentioned the MTHFR gene mutation, but I should also make you aware of another genetic condition called pyrrole disorder, or pyroluria. A pyrrole is a normal by-product of haemoglobin synthesis and is normally excreted in the urine. Although pyrroles have no function in the body, they do have an affinity for zinc and active B6 (P5P) and can be transported out of the body together with the pyrroles. Those with the genetic condition, when under chemical or emotional stress, find they produce an abnormally large number of pyrroles, seriously depleting zinc and P5P levels.

As you are now aware, low levels of zinc and P5P are linked to many mental health and behavioural disorders.

Poor gut health – The gut-brain connection

link between brain and your gut bacteria

A healthy gastrointestinal tract allows us to absorb essential nutrients from the food we eat, and filter waste and toxins from our body. A healthy gut contains a diverse community of microbes that help us fight infection, produce certain vitamins and even produce neurotransmitters!

Unfortunately, we destroy our gut daily, with the processed foods we eat, the medications we take and the chemicals we are exposed to.

Our gut wall contains tight junctions between the cells designed to allow small nutrient particles into the blood stream and keep toxins out. But when our gut becomes “leaky,” our body is overloaded with undigested food proteins and potentially harmful microbes, metals and chemicals, resulting in an inflammatory immune reaction.

leaky gut diagram showing a normal and abnormal tight junction

What increases the permeability of the gut? Food sensitivities (like to gluten), chemicals, a candida overgrowth and infection. Vitamin D, A and zinc are thought to help keep the gut junctions “tight.”

Chronic stress

Emotional stress has also been shown to increase the permeability of the gut (make it “leaky”).

Overproduction of the stress hormone cortisol can lead to inflammation and a decrease in serotonin synthesis as it shunts tryptophan down a different pathway.

Excess cortisol can influence the production of hormones like progesterone, insulin, TSH and thyroid hormones. It can suppress the immune system and have an impact on fertility, sleep, digestion and cardiovascular health.

Essentially, stress is a killer! Even the World Health Organisation agrees when it stated:

“Stress is the health epidemic of the 21st century.”

It wasn’t until I graduated that I realized Prozac was not the answer for me.

clouds and rain over a graphic of a person's brain

To discover what was really at the root of my depression, I needed to go deeper and ask what was causing the imbalance and how I could support my body better.

My gut health was poor. My diet was devoid of nutrients and high in sugar and alcohol. I was on the oral contraceptive pill, which further depleted vital nutrients. Stress, a candida infection, a gluten sensitivity and little exercise increased the permeability of my gut, allowing toxins to enter the bloodstream where they caused an inflammatory “fire” within my body. My poor brain and body couldn’t cope.

I needed to remember that my body was simply responding to its environment, and I needed to provide it with better conditions. When it comes to understanding and addressing mental health issues, we need to consider all stressors on the body—physical, chemical and emotional. We must start looking upstream and address the underlying causes naturally.

Medication has its place. Please do not suddenly stop taking any anti-depressants or mood-altering medications. They can help you through those challenging times, while you swim upstream, hopefully with the help of a friend and a holistic health professional.

Counselling and psychotherapy is also important, particularly if trauma and emotional stress or abuse are a factor. There is also the impact of social factors like poverty, isolation, migration and employment to consider.

However, mental health is multi-factorial. There are additional questions that need to be asked.

Does my diet need an overhaul? Do I have “dirty genes”? Do I need nutrient supplementation? Can I manage stress better? Do I need to exercise more? Is heavy metal toxicity a possibility for me? Is my home damp and mouldy? Can I reduce my toxic load by changing my personal and home care products? Could depression be a side effect of a medication I’m on? Do I need to heal my gut, address an underlying infection or avoid certain foods?

I do sometimes wonder how many incarcerated in a mental health facility or even jail could have been helped if we looked closer at their microbiome, nutritional deficiencies, toxic burden and genetic makeup. New thinking is required if we truly want to address the mental health crisis we’re facing. Essential for success is a truly holistic, integrated and collaborative approach, because doing more of the same is not working.

image of healthy food and functional medicine practitioner Georgina Compton

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