Understanding and conquering depression

Written by : FENILKUMAR NITINBHAI RIBADIYA, CLASS OF 2023

Depression has two forms: bipolar depression and major depression, also called unipolar depression.

Bipolar depression, sometimes called bipolar disorder, is characterized by manic highs followed by periods of crashes, feeling very low and lethargic. However, in this blog, we are discussing major depression because it doesn't have the highs and lows. It's more characterized by continuous lows.

Major depression affects around 5% of the population. That means if you’re in a class of 100 people, 5 of them are dealing with major depression or have at some point in their life dealt with it. Before moving forward, it is necessary to understand that accurate diagnosis and treatment of any mood disorders requires advice from qualified healthcare professionals.

Clinical depression has specific diagnostic criteria, including a lot of grief, sadness, anhedonia (a general lack of ability to enjoy things), guilt, and antiselfconfabulation (as if a brain circuit that writes stories just starts generating content), along with a threshold to cry, which is often considered a signature symptom of depression.

Other symptoms include vegetative symptoms, which occur without any thinking or doing, such as early waking and not being able to fall back asleep despite being exhausted, and decreased appetite.

Understanding which hormones are involved, their relation to specific symptoms, and the brain circuits affected in major depression can help in overcoming this condition. Additionally, there are scientifically proven behavioral tools that can adjust the level of a particular hormone and provide relief for some symptoms of major depression, even helping to lower the required dose of medications. However, effectiveness will depend on the individual.

In this blog, you will learn about why different hormonal changes are the culprit behind major depression and how to conquer it.

Epinephrine is thought to be related to the so-called psychomotor defects, and a reduction in epinephrine is behind the lethargy and exhaustion.

Dopamine is thought to be related to anhedonia. Serotonin is thought to be related to grief, guilt, and other emotional aspects of depression.

Serotonin, also called 5-HT, essentially derives from a precursor called tryptophan, which is found in turkey and carbohydrates. Tryptophan is eventually converted into serotonin.

Now, there is growing evidence that many forms of major depression, if not all of them, relate to excessive inflammation. This inflammation can lead to or exacerbate depression, and focusing on reducing inflammation and its associated pathways is a really good thing to do. When we are chronically stressed, inflammatory compounds like IL-6, TNF-alpha, and C-reactive protein cause inflammation of brain cells, in particular glial cells, which are typically thought to be support cells. These cells start to become disrupted.

These inflammatory cytokines act in a variety of different ways, but they mainly act to inhibit the release or synthesis of serotonin, norepinephrine, and dopamine.

To limit inflammation and to relieve some or all of the symptoms of major depression, one approach is to increase our intake of socalled EPAS or essential fatty acids. When people ingest a certain level of EPA, like omega-3 fatty acids, the relief from depressive symptoms matches the effect of SSRIs. Some studies have shown that increasing our intake of these essential fatty acids, in particular the EPA variety of omega3s, can lower the effective dose of the SSRIs. The threshold level seems to be about one gram or 1000 milligrams of EPA.

Another deeper biological phenomenon to understand is that these inflammatory cytokines cause tryptophan to not be converted so much into serotonin, but to be diverted down a different pathway involving something called IDO or indole amine, which converts tryptophan into kynurenine.

Kynurenine actually acts as a neurotoxin by way of converting into something called quinolinic acid, which is pro-depressive. Under conditions of inflammation, tryptophan that normally would be made into serotonin is being diverted into a neurotoxic pathway. Ingestion of EPAS limits these inflammatory cytokines, which can cause more of the tryptophan that one ingests or has in their body to be diverted towards the serotoninergic pathway that will eventually increase the amount of serotonin.

A second approach is regular exercise. It turns out that it also has a positive effect on the tryptophan to serotonin conversion pathway. In particular, aerobic exercise but also resistance training to some extent tends to sequester neurotoxin and further augments this conversion of tryptophan into serotonin. By getting EPAS from typical food or supplementation and doing regular exercise, we can converge on a common pathway and increase serotonin.

So let's think about WHY this behavioural tool would help you relieve depression. The answer to that is that drugs given to treat the symptoms of major depression, such as SSRIs, SNRIs, and MAO inhibitors increase the amount of noradrenaline, dopamine, and serotonin in the brain. However, tools such as EPAS and exercise are not a replacement for treatment given for depression; rather, they help individuals maintain healthy levels of these hormones in the body, which can make them feel happier and more socially connected.

If you are taking any medication, it is advisable to consult a medical practitioner before implementing these tools.

Summary of the behavioral approaches to conquer depression :

1. Increase the intake of EPAS or essential fatty acids.

2. Carrying out regular physical exercises.