The Biology of Stress and Depression Pt. 3: Pregnenolone

(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)

Hello again,

Welcome to our third post on the biology of Stress and Depression.  Just to recap the previous posts, please review the following:

The current model regarding the problem of depression sees it as a lack of neurotransmitters (dopamine, serotonin & nor-adrenaline). This view sees depression as a “lack of happiness”. If you want to treat a depressed patient you give him/her drugs to increase the presence of these deficient hormone(s).  Increasing amounts of these hormones should, in theory, make people happier. The trouble is that in the light of other theories of depression, this theory is very limited.  In addition, it does not take into account the impact of stress on the body.

Current research clearly shows us that stress leads to depression.  Excessive amounts of stress lead to the gradual destruction of the hippocampus.  The hippocampus controls the the body's reaction to stressors. Increasing amounts of stress and the consequential destructive impact on the hippocampus lead to a reduced ability to handle further stress. It can become a vicious cycle.  That cycle is highlighted by research finding that untreated stress/depression is linked to having a smaller hippocampus which in turn is directly linked to being predisposed to depression, largely because of reduced ability react appropriately to stressors.  Clearly, stress does lead to depression. 

Note that stress is also often regarded as something people have control over. This is often not the case.  Stressors are not just psychological. They can be biological or physical in nature and either is often completely out of our control.  

In order to cut depression off at the source, we need to find ways to deal with stress. One step, which your body does naturally, is to produce a neurochemical called pregnenolone. Pregnenolone is a steroidal hormone produced naturally in the body. Pregnenolone is a precursor hormone synthesized from cholesterol. It is primarily found in the adrenal glands but it is also generated by the liver, skin, brain, testicles, ovaries, and the retina of the eyes. Pregnenolone may be one of the most important neurochemicals because it seems to have a regulating effect on other steroidal hormones.

Steroids in general are a large group of structurally related biochemicals that encompass anti-inflammatory, sex-determining, and growth-regulating functions. Pregnenolone is the grand precursor from which almost all of the other steroidal hormones are made.  These other hormones include: DHEA, progesterone, testosterone, the various estrogens, and cortisol.

Pregnenolone has been shown to be up to 100 times more efficient for memory enhancement than other steroids or steroid-precursors, in laboratory animals. Pregnenolone seems to be the most powerful memory enhancer ever reported on in animal studies. Pregnenolone has been reported to not only make people sharper mentally, but also happier.  It’s also may enhance the ability to perform on the job while consecutively heightening feelings of well-being.  Not surprisingly, pregnenolone has also been reported to reduce high stress induced fatigue. Its importance in decreasing the impact of stress is significant.

Effects of pregnenolone also include stress reduction and increased resistance to effects of stress, improvement of mood and energy, reduced symptoms of PMS and menopause, improved immunity, and repair of myelin sheaths. Myelin sheaths are like insulators on your nerves. They help make sure that electro/chemical impulses say strong and going in the right direction along the nervous system. Pregnenolone also functions as a potent neurosteroid in the brain. It controls and strengthens the transmission of messages from neuron to neuron and strongly influences learning and memory processes.

As is the case with other steroid-hormone precursors, pregnenolone levels decline with age. By the age of 75 our bodies produce 60% less pregnenolone than the levels produced in our mid-thirties. For this reason pregnenolone is considered one of the biomarkers of aging. Like counting the rings of a tree, by evaluating the level of pregnenolone at any given point of a person's life, it is often conceivable to make a guess as to their age.

Other hormones which decline with age are: DHEA, the estrogens, testosterone, progesterone and growth hormone. These are also considered biomarkers of aging. Pregnenolone provides the initial raw material from which most steroid hormones are made. Consequently, many of the bodies' other hormones will decline in a parallel fashion.

How does pregnenolone relate to depression?  Please review the following list of effects it has on the nervous system in general.

Enhancing Memory and Cognition

Increasing acetylcholine levels, improving neurogenesis (the formation of new neurons), and adjusting gamma-aminobutyric acid (GABA) are among the avenues pregnenolone uses to increase memory and mental function.  Acetylcholine is a critical neurotransmitter that assists brain cells in communicating with each other. Many Alzheimer’s medications ( Aricept® and Reminyl®) work by reducing the breakdown of acetylcholine. In a recent study, French researchers discovered that infusing pregnenolone sulfate (a sulfated derivative of pregnenolone) into the brains of rats boosted acetylcholine release by 50% while improving cognitive recognition of a familiar environment.

Neurons created through neurogenesis are cells that send and receive electrical signals to and from other parts of the body.  This is a vital mechanism in both humans and animals. The potential to boost neurogenesis gives hope to those with chronic, debilitating diseases such as Alzheimer’s, Huntington’s and Parkinson’s.  Aware that neurogenesis is sensitive to hormonal influences, researchers in the study mentioned above examined the effect of pregnenolone sulfate on neurogenesis in young and old rats.  Infusion with pregnenolone sulfate increased nerve growth in both 3- and 20-month-old rats. The researchers concluded that pregnenolone could prevent the appearance of age-related cognitive disturbances.

GABA is another critical neurotransmitter related to proper mental function.  An inhibitory neurotransmitter that aids in relaxation and sleep, GABA acts as a “balancer” for the brain, helping us balance excitation with inhibition. There are encouraging indications that pregnenolone may both inhibit and enhance the activity of GABA receptors, thus helping modulate nervous system function.

Countering Fatigue and Stress

As was discussed in previous posts, there is a direct connection between excessive stress and depression. This included a discussion of ways in which treating stress and depression may lead to cognitive improvements.

A research group studied pregnenolone effects on improving job performance in students and workers. They found that pregnenolone helped both groups learn and remember tasks which were challenging enough to be stressful. Pregnenolone not only boosted job performance, but it also helped produce heightened feelings of well-being in the test subjects as well as decreases in fatigue.

During periods of stress, our output of adrenal hormones increases. Increased output of these hormones has been associated with increased fatigue in army pilots, resulting in poor performance. In a study of pilots under stress, 50 mg of pregnenolone daily improved performance with no adverse side effects.

Combating Depression

Antidepressant medications not only are associated with a host of adverse side effects, including: loss of libido, weight gain, constipation, and insomnia, but also do little to address underlying foundations of depression. Numerous studies demonstrate that a deficiency of pregnenolone may be  a much stronger link to depression than deficiencies in neuro-transmitters such as dopamine, serotonin and nor-adrenaline .

In one study, subjects with either current depression or a history of depression exhibited significantly lower levels of pregnenolone than non-depressed individuals. Additionally, patients with active depression had lower levels of pregnenolone compared to those in remission but with a prior history of depression. 

Pregnenolone has a defined role in mental health.  The goal of this post is not simply to encourage supplementation. Rather, the aim is to shed light on other aspects of depression that are not currently being addressed by anti-depressant medications.  Future posts will be looking into other hormones and factors related to depression.

Stay Tuned!

Healing Sounds Introduction

A very quick introduction to healing sounds qi gong. In this video, David Lloyd from Crane Medicine in Milton Ontario explains how healing sounds work.

www.cranemedicine.com

The Biology of Depression & Stress Pt. 2: Cortisol

(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)

Hello again,

This blog post is the second in a series of posts that we will be doing on Depression & Stress.  

In the previous entry (click here to see it), we discussed the fact that the current model for the treatment of depression revolves around one central theme.  That theme is called the biogenic amine hypothesis.  This theory views the cause of depression as a lack of key neurotransmitters (nor-epinephrine, serotonin & dopamine).  The drugs currently being used to treat depression only focus on increasing these chemicals in the body, theoretically adding gas to a depressed person’s fuel tank.

This theory appears to be helpful in some people, but not all, in fact not even half.  That is the purpose of this series of posts we are doing on depression, to look into other theories than just the standby concept.

Depression is clearly a physical problem.  The lack of motivation, aches and pains, and increased general disease risks, make it clear that depression has roots deeper than just the emotions alone.  Further these risks relate to an extended period of time.  This means that there must be long-term factors that pre-dispose people to depression (no, we are not talking about inheriting depression from your parents).

A major factor predisposing people to depression is stress.  Stress impacts the body through something

called the Hypothalamic Pituitary Adrenal axis (HPA).  The hypothalamus is the main regulator of all the hormones in the body.  The hypothalamus releases something called corticotropin releasing hormone (CRH), and that goes down to your pituitary gland.  Your pituitary gland is often called the “master gland” of the body.  Your pituitary releases factors that influence all of your other glands: thyroid, adrenals, pancreas, sexual organs … you name it.  The pituitary also releases something called Adrenocorticotropic hormone (ACTH).  The name explains what it does: Adreno refers to the adrenals, cortico to cortisol and trophic means to stimulate.  ACTH stimulates your adrenals to release cortisol, a major stress hormone. 

The take way from this science is this: once your pituitary gland is stimulated to release CRH it starts a chain reaction of events that lead to increased stress hormone levels in the form of cortisol. 

So … that’s it!  Crush cortisol and we’re cool calm and collected … right?!  Not so fast.  Cortisol is vital to the human body.  Without it, you’ll die.  But, it should be available in short term and/or low grade doses, not the amounts that stimulate a fight or flight response.  You need to moderate it. 

The problem with chronic overstimulation of cortisol production is that it travels back into brain.  The brain is very receptive to cortisol.  It makes sense, since this hormone is designed to save us from hungry bears.  However, the calm state of happiness that we all seek doesn’t fit well with running for your life.  In fact, cortisol alters levels of serotonin dopamine and nor-epinephrine (please see our first post about these happy hormones).  This is a cornerstone of the current thinking regarding what causes depression.  But the root of the problem is not a lack of hormone; that is just a symptom.  The REAL problem is the suppression of happy hormone production caused by stress.

This is your hippocampus on stress and full of holes

How can cortisol be destructive?  A seminal study done by Robert Sapolsky back in 1983 found that stress hormones cause brain damage. What he did to discover this was take rats and plant a placebo or a slow release form of cortisol in different sections of their brains.  The area of the brain that he was studying was the hippocampus.  The hippocampus has two functions that are vital to our discussion here: management of stress hormone levels and establishment of long-term memories.  Guess what?  The implanted stress hormones killed off a massive amount of cells in the brain in comparison to the placebo.  What this tells us is that prolonged exposure to high levels of stress will kill your neurons and brain tissue.  New evidence has emerged that supports this idea in humans.  The average hippocampus of depressed people has been shown to be smaller than undepressed people by about 15%.  It gives you something to think about regarding the loss of memory during traumatic events; it also shows how the poor regulation of stress can lead to brain dysfunction.  They also feed each other … it’s a slippery slope in a lot of ways … if you lose hippocampal cells the lining on breaks go.  Once the breaks go on your hippocampus, you can’t control the flood of stress hormones.  These stress hormones further damage your hippocampus and the cycle continues.

This lends some scientific support to the idea that depression leads to other health problems.  It’s long been known that excessive stress can lead to ill health.  Now you can see that depression is just the end stage of excessive stress hormone production.  The good news is that if you start taking steps to treat your depression, you can stop the wave of problems that come with depression.

In 2003, Yvette Sheline published a paper studying the function of the hippocampus in untreated people with depression.  Take a look at the chart for people with untreated depression.  But if you treat depression, Sheline found that it protected the hippocampus.  This is very reassuring.  If you treat depression, it saves your brain.  This means that treating depression may be neuro-protective.  It also means that toughing depression out and just living with it may be damaging your nervous system, and not something to be courageous about.

In this post we established the idea that stress is damaging your nervous system, and we gave you a direct link to how excessive stress may lead to depression.  Further we’ve shown that when you start to put the break on depression, you can shortcut the cycle and may actually save your nerves and brain from further damage.

In our next post, we will go into ways that you can take action to reduce stress and protect yourself against the negative health consequences of depression.

Stay Tuned!

David

Tea: Health benefits and a brief history

Please note: While herbal “teas” can be brewed from a variety of leaves, flowers, or roots, in this article we focus on tea leaves. Tea – Oolong, green, white, yellow, red and black – comes from the leaves of the Camellia sinensis plant. The difference in taste and health benefit comes from the way the tea leaves are processed: to make black tea, the leaves are fermented, which neutralizes many of the antioxidants present in the leaves, while oolong / white / yellow / green tea is produced by lightly steaming the fresh-cut leaf. At the end of this article we will be discussing several additional herbs that may be added for further health benefits.

A SHORT HISTORY…

There are many old sayings in Chinese on the value of tea.  One however shows the immense value customarily placed on tea. It reads: “Better to be deprived of food for three days, than tea for one.” That is quite a strong statement, but it is also very telling of the new scientific research backing up this tradition.

The tea leaf has branches in many places, but its roots are in China. As legend has it, a man named Shen Nong, who is considered the father of farming and medicine in China, discovered tea in the process of developing a written account of the medicinal use of herbs. History says he was poisoned one day after eating more than 60 herbs. He then used tea to balance / detoxify the poisonous effect of the herbs, thus saving his life.

Before the people of ancient China consumed tea as a daily beverage, it was used as medicine. The use of tea leaves is categorized as “clearing heat and purging fire.” The traditional medical indications for drinking tea mainly consist of digestive conditions such as nausea, vomiting, and diarrhea. However, the treatment of headaches and reducing excess fat in meat-heavy meals are also included in its use.

CALM YOUR SPIRIT …

Another interesting association with the tea leaf is its strong connection to the monastic traditions throughout Asia. Hermit monks living in the mountains of China grow tea near their huts. A lovely poem by an anonymous monk reads: “The singing kettle sounds like a cicada pouring forth his woes to the departing summer.” Tea is traditionally said to relax the mind and calm the spirit. But wait, what about its caffeine content?

Researchers have often wondered why tea, despite its stimulating caffeine content, tends to calm one’s spirits without making them drowsy. Furthermore, mountain monks who engage in meditation drink tea to dispel mental sluggishness, and yet do not become mentally agitated. The answer is a rare amino acid in tea called L-theanine. This amino acid is the component in oolong / green tea that is largely responsible for its relaxing benefits.

Many tests have demonstrated the anti-stress effects of L-theanine. One of the more revealing of these experiments examined brain wave patterns after the ingestion of L-theanine. In this study, fifty volunteers were divided into high-anxiety and low-anxiety groups. Each group was given either 50 or 200 mg of isolated L-theanine in water once a week. Their brain waves were measured during the hour after ingestion. The results showed marked increases in relaxed wakefulness roughly 40 minutes after ingestion.

OTHER HEALTH BENEFITS …

Animal studies have shown oolong / green tea, or its extracts, to be effective against chemically induced cancers. These cancers include: lung, breast, colon, liver, skin, and a variety of gastrointestinal cancers. Furthermore, oolong / green tea extracts have been found to protect animals from certain types of prostate cancer.

Human evidence for the health benefits of oolong / green tea consumption is also impressive. Extensive evidence shows that people who consume high amounts of oolong / green tea live longer, develop less cancer, have healthier cholesterol levels, and suffer less cardiovascular and liver disease.

How to Brew – Use one teaspoon of loose-leaf green or oolong tea per cup of water. Brew for 2 to 3 minutes using water that has just begun to steam – not yet boiling. Most high quality loose-leaf teas can be re-used several times. 

BOOSTING YOUR BENEFITS …

Modifying your tea is a simple and delicious task that has many added health benefits. Below are three herbs, each with their own special effect on the body. In order to modify your tea, go to a Chinese herb shop and buy a bag of one of the following herbs, and add a handful of the chopped ingredient and let it steep with your regular tea leaves. You can just add one, all three, or combine them as you wish.  Write down the Mandarin names and show it to the people at the shop, and they will direct you to the herbs in question.

• Fructus Jujubae, Da Zao in Mandarin, or simply Chinese date in English, is a potent and tasty add to your regular tea. Make sure to add the kernel at the center, crack it open with scissors or pliers. This will unlock the most potent part of the herb. Chinese dates have a long list of traditional indications, including: boosting digestion, generating strong blood cells, calming the spirit, and reducing the toxicity of other herbs. Chinese dates also have a sweet taste, making them perfect after a hearty meal.

• Fructus Lycii, Gou Qi Zi in Mandarin, or simply Goji Berries in English, are another strong and tasty way to modify your regular tea. Goji berries are an incredibly valuable daily tonic. They too have a long list of indications, including: brightening the eyes, moistening the lungs, generating fresh and strong blood, and boosting virility.

• Arillus Longan, Long Yan Rou in Mandarin, or simply dried longan fruit in English, is a wonderful addition to your regular cup. Both sweet and warm in nature, this herb is used to boost heart and digestive function. It is also used to simultaneously bolster Qi, the body’s vital energy, and blood. This is a commonly used herb to strengthen the body after giving birth or a long illness.

Conclusion …

As the ancient Chinese would have said, “A drop of water shall be returned with a burst of spring.” The meaning of this saying is that even if it was just a little help from others, you should return the favour with all you can when others are in need. This is a perfect saying when it comes to your tea, just a teaspoon can go a long way for your health. Bottoms Up!

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