Biological Depression: We feel with our brain, not our hearts

If Stanford Professor Robert Sapolsky were asked to define Major Depression in one sentence he would say that it is a BIOCHEMICAL disorder with a GENETIC component where EARLY CHILDHOOD experiences influence why a person cannot appreciate sunsets. Amazingly concise. Amazingly accurate. And amazingly true.

Sapolsky states that we humans have an astounding capability to derive pleasure from the most unlikely domains. So what could be more devastating than a disease whose main symptom is the inability to experience pleasure?

Major Depression is characterized by the following symptoms:

1) Anhedonia – The inability to feel pleasure

2) Grief and Guilt – Not your ordinary grief but the kind so severe that it takes on a delusional quality. This does not necessarily mean hearing voices but means that there is a propensity to obsess or focus solely on what is negative. A person who is in normal grief will grieve the loss but is able to see beyond the loss. Grief associated with Major Depression just obsesses over the loss and nothing else.

3) Self-Injury or suicide

4) Psychomotor Retardation – The inability to do anything due to severe exhaustion. Everything feels like it requires too much energy. When a depressed person is in this state there is little risk of suicide because even planning a suicide takes too much energy. it is when they start to lift from this state and begin showing some improvement that suicide presents a real threat.

5) Vegetative Symptoms:

Sleep: This does not necessarily refer to the inability to sleep but to the disruption of normal sleep patterns. A classic sign of major depression is waking up too early. In the brain of someone who is in Major Depression the whole structure of sleep and its patterns are in disorder.

Decreased Appetite: Normal tendency for run of the mill depression is to compensate by bingeing in order to fill the feeling of emptiness. In major depression there is no effort to fill in the loneliness and the void.

Stress Hormones: Stress hormones are elevated because there is a constant activation of the stress response. The Sympathetic Nervous System is constantly agitated resulting in the release of hormones such as Adrenaline and Cortisol. These hormones cause increased metabolic rate, increased muscle tone and raises activity inside the body. This is why depressed people feel so tired all the time.

To understand the disease, one has to understand its biological component, its psychological roots and how the two can be connected. Let’s start with biology.

An idiot’s guide to BIOCHEMISTRY ( as understood by another idiot)

Our brains work by sending chemical signals from Neuron to Neuron. The space between neurons is a liquid filled space called a Synapse. Messages are brought from neuron to neuron across the synapse by Neurotransmitters. There are hundreds of neurotransmitters that are passed from neuron to neuron, each with a different function. Three neurotransmitters have specifically been associated with Major Depression – norepinephrine, dopamine and serotonin.

The first proof that depression can be caused by a chemical imbalance is the discovery that depressed people do not have enough Norepinephrine in their system. Normally, norepinephrine is recycled or destroyed as soon as the “message” is fired in the synapse. ¬†Medication for depression can include medicine that stops the recycling and destruction of the norepineprine so it stays in the synapse longer and is able to send its message to the next neuron repeatedly, compensating for the lack in Norepinephrine in the system. Norepinephrine has been described as the “pleasure pathway” in the fifties. it was believed to be responsible for the feeling of pleasure. But they soon discovered that norepinephrine was only a minor player in the pleasure pathway. Scientists discovered that Dopamine had an even more significant effect in the pleasure pathway. It is no surprise then that Cocaine and Met amphetamine, which act directly on the Dopamine system, have become highly addictive and abused drugs. In the late 80s, Prozac was invented. Prozac is an SSRI or a selective serotonin re-uptake inhibitor was discovered to make depressed people better. Serotonin was therefore also discovered to be very crucial in the level of pleasure or happiness that a person can feel. To be insanely simplistic, what scientists discovered is that too little Dopamine can cause ANHEDONIA or the loss of pleasure, too little Norepinephrine had something to do with the PSYCHOMOTOR RETARDATION and the absence of Serotonin had something to do with the obsessive feeling of GRIEF; all of which are major symptoms of Major depression.

Psychic Pain is just as real as Physical Pain

What is also very interesting is the discovery of the neurotransmitter called Substance P. Substance P is an important element in pain perception. Substance P is what transmits pain information to our central nervous system. Substance P is what tells us that we stubbed our toe or that our whole body is burning.  It was discovered that when medication which reduced Substance P in the body is given to depressed people, it makes them feel better. This suggests that psychic pain is not just a metaphor but that it is actually regulated by the same neurotransmitter than transmits information about physical pain. The pain depressed people feel is REAL.

The Limbic System: The part of the brain that regulates emotions

There is evidence that the Limbic System which is the part of the brain which is responsible for our emotions (fear, lust, anger, rage, love etc.) can affect our reptilian brain, which is the part of our brain that controls our “regular plumbing”. The reptilian brain is what regulates our blood pressure, makes our limbs move this way and that, basic operational stuff in our bodies. The cortex,which is the biggest part of our brain is responsible for our logic — it is what we really use to THINK. When we are physically hurt such as when we meet an accident and get hit by a car, the cortex activates our body’s stress response. Simplistically speaking, in a depressed person, the cortex convinces the rest of the brain that the sad thoughts and feelings are real, as real as if we were hit by a car or gored by a wild animal. And because of that the body physically reacts the same way and triggers a stress response.This is why in extreme cases where every type of therapy has already failed, there is Cingulotomy, where the connection between the cortex and the limbic system is severed. Unfortunately, while this relieves depression, it also robs the person with the capability of experiencing pleasure.

Hormones and their role in Depression

People diagnosed with Hypothyroid have low levels of thyroid hormones and people with this disease always go through major depression. 20% of major depressions are undiagnosed hypothyroid problems. The thyroid regulates metabolism and people with lack of thyroid hormones tend to feel sluggish, gain weight easily and have difficulty losing weight despite increased activity.

Women are twice as likely as men to have depression and many instances indicate that these also have to do with hormone levels. Women tend to have major depression at particular periods when their hormones are going haywire — PMS, Post partum depression etc.

All of these… neurochemistry, the structure of the brain and hormonal changes all scream biology. The physiological connection to depression is irrefutable. It truly is as much a biological disease as diabetes and cancer.

(Psychological Aspect of Depression to follow in the next blogpost)