Depression: Have You Considered These Causes?

Updated: May 11

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, the stress response, emotions, energy, cravings, pain and more. They are nerve system messengers that facilitate communication between the brain, glands, organs and muscles.

Also communicating vital messages are hormones. Released from endocrine glands into the blood stream, 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.

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.

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