The Biology of Depression & Stress Pt. 1: Why the Current Theory Fails So Often

(These are all of the posts we have on this topic)

1st Post on Stress and Depression Why the Current Theory Fails So Often

2nd Post on Stress and Depression Cortisol

3rd Post on Stress and Depression Pregnenolone

4th Post on Stress and Depression DHEA

5th Post on Stress and Depression BDNF
6th Post on Stress and Depression: The Cholesterol/Dopamine Connection
7th Post on Stress and Depression: Increasing levels of Brain Derived Neurotrophic Factor (BDNF)

The "mind" and the "brain" are an interesting dualism. The brain, as seen in biology, is essentially an impersonal and somewhat mechanical circuit of biochemistry. The mind on the other hand is considered unique and individual. Each mind has its own storage of memories and experiences. As we move forward in this blog today we will be looking at the chemistry behind what causes depression and its relationship to what we experience in our minds as depression.

Why do we care about depression? What are the burdens of depression in our everyday lives? What follows are statistics regarding major depression (medically significant depression, not just feeling down for a day):

 • Retrospective studies (looking back at recorded cases) show a lifetime incidence of major depression of 16%.

• Prospective studies (looking forward toward expected rates of depression) suggest twice that rate of occurrence.

• More people suffer from major depression (US Statistics of 40 million) than heart disease (12 million), cancer (10 million) and HIV/AIDS (1 million) combined.

• Major depression is the leading cause of disability in North America, and by 2020 it is projected to be the leading cause world-wide.

• Major depression costs over 30 billion dollars each year in the US alone.

• Nearly 30% of people with major depression report suicidal thoughts.

What has been the prevailing theory explaining depression since the late 1950’s? When we go to the doctor and get treated for depression, what is the protocol, or theory which determines the treatment we receive? The traditional theory is called the biogenic amine hypothesis. It views a case of depression as though it is the result of a deficiency of certain chemicals in the brain (nor-epinephrine, serotonin & dopamine). Therefore, their amounts need to be increased to solve the issue of depression. This is partly true, but this begs the question, "If this is the solution to the problem why are there still so many people in the world that are still depressed?" Even using this current model of thinking, it is a fundamental fact in the treatment of depression with drugs that there is no approved laboratory test that can tell a doctor what type of depression you actually have. Treatment involves a shotgun, trial and error approach which can see patients bombarded with medications in the hope that one of them will work.

Why do we need a new model for looking at the treatment of depression? According to the current theory, depression can be improved by various drugs that increase the availability of two types of neurotransmitters, namely: noradrenaline and serotonin. Many of the drugs used to treat depression decrease something called “monoamine oxidase” (MAO), which degrades the neurotransmitters previously mentioned. In theory, blocking the action of MAO will lead to an increased amount of the neurotransmitters needed to fight depression. Sounds great in theory, but there appears to be a lot more involved in depression than just neurotransmitters.

In the 1950s, drugs were developed that blocked the re-uptake in the process described above. These drugs - still widely used today - are called tricyclic antidepressants or TCAs. The Biogenic Amine Hypothesis has been the cornerstone of research on depression for more than 30 years. However, an important fact cannot be explained by this prevailing theory. Laboratory tests indicate that antidepressants such as TCAs and MAOIs increase available neurotransmitters quite rapidly, often within a matter of hours. Yet, typically, clinical relief seems to take a lot longer. A person suffering from depression may not experience any level of relief for up to 6 to 8 weeks.

Further:

• Current models do not explain why some people are susceptible to depression, while others are not.

• Current treatments we use today were largely discovered by accident, unguided by evidence of biological pathology (the first anti-depressant drug was an anti-tuberculosis drug that had the side-effect of making people happy, even though they were locked in a sanatorium).

Current models are based on the response of the body to certain drugs, not an underlying knowledge of what cause is being treated. So, the side-effect of this drug is a better mood … why does that happen when you take said drug? Oh, it increases “x” chemical … so that must be what is causing depression.

Almost of the drugs being used today are “me too” drugs. Zoloft, Selexa, Paxil and Lexapro all work to a degree, but they don’t work any better than the earlier medications used decades ago, though they have fewer negative side-effects. They are also rebranded to make more money. This means that ALL drugs are based on one idea. An idea that has never been fully explained. Furthering the need for a new model to treat depression, we know from clinical use (actual use of treatment, not just based on an idea or a theory) that current treatments are not fully effective. They only work on some types of depression. The reason for this is likely in large part because the diagnostic criteria are based on the following non-laboratory based symptoms from something called the "DSM" (diagnostic manual for psychologists):

• Depressed mood most of the day.
• Diminished interest or pleasure in all or most activities.
• Significant unintentional weight loss or gain. • Insomnia or sleeping too much.
• Agitation or psycho-motor retardation noticed by others.
• Fatigue or loss of energy.
• Feelings of worthlessness or excessive guilt..
• Diminished ability to think or concentrate, or indecisiveness.
• Recurrent thoughts of death

In some patients, these symptoms may be caused by a lack of the neurotransmitters.  In this case the problem would be addressed by the prescribed drugs. In others, they might look the same on the surface but have completely different root problems. These root problems may have nothing to do with the neurotransmitters that these prescription drugs alter.

The reason for this is that people are being prescribed medications without actually measuring their blood for a deficit in the neurotransmitters. The drug won't help if it is not needed, this is the root of many of the side effects caused by pharmaceutical drugs. Also, if depression is strictly a problem of the mind … why then do people with depression suffer from higher rates of chronic disease? Heart disease, stroke, diabetes, osteoporosis & dementia are all higher in people with depression. This clearly points to a problem that involves the entire body and not just the brain.

In a series of upcoming blog posts we will be examining several new and exciting frameworks for what causes depression, as well as what you can do about it!

Feel free to comment and share these posts.  The world is a dark place for some of us, the goal of these up coming posts is to bring some light to those who need it.

Stay Tuned!

Yours,
David