The Biology of Stress and Depression Pt. 4: DHEA

(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)

Welcome to the fourth post on the biology of Stress and Depression.  Just to recap important information from the previous posts, please review the following:

The current model regarding the problem of depression (that most medical providers believe) 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 explanations 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 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 reinforced 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. This is largely because of reduced ability react appropriately to stressors.  Clearly, stress does lead to depression. 

Note: stress is often regarded as something people have control over. This is often not the case.  Stressors are not just series of thoughts. Stress 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 all forms of stress. 

In the previous post we discussed a neuro-hormone with anti-depressant properties called pregnenolone. In this post we will be discussing another important neuro-hormone involved with stress and depression called DHEA.

DHEA is an abbreviation for dehydroepiandrosterone. Levels of DHEA peak in your 20's and slowly fall as you age. By the time you reach 40, your body makes about half as much DHEA as it used to. By 65, levels drop to 10 to 20 percent; by age 80, it plummets to less than 5 percent.

DHEA is a hormone made primarily by the adrenal glands. Hormones are chemical messengers that affect the function of cells and tissues all over the body. DHEA and cortisol are long-acting stress hormones and they are inversely related to each other. If one of these hormones goes up, the other goes down. They also have opposing functions.  Where DHEA has an anabolic or regenerating influence, cortisol has a catabolic or degenerating effect. Both of these hormones are indispensable, but they must be in proper balance for optimal health. How does the relationship between these hormones become unbalanced? The short answer is "stress maladaptation".

Stress maladaptation refers to an inappropriate response to prolonged stress. The typical reaction of the body to a stressor is to produce adjusted amounts of both cortisol and DHEA. When the stress is gone, the body readjusts its output of both cortisol and DHEA to resting levels. Both return to an appropriate baseline. This is what happens with short episodes of stress. However, when the stress is prolonged, the body begins to increase levels of cortisol while reducing levels of DHEA.  How long does it take for this to happen? One study showed that after just 28 days of constant stress, cortisol levels had climbed to 240 percent and values for DHEA had dropped to 15 percent of original levels! What's worse is that even after the stress is removed, the body sometimes does not recover and bring these hormones back to normal baselines. Instead, it remains in the stress response mode with high cortisol production and low DHEA output.

Remember, stress and its ever present partner cortisol shrink and erode your hippocampus.  A happy, healthy and large hippocampus is a major factor in avoiding depression.  Poor stress management and the resulting DHEA deficit are a major factor in depression.  In fact, DHEA supplementation has been shown to promote neurogenesis (regrowth of new nerve tissue) in the hippocampal regions of rats which have been artificially stressed with high levels of injected cortisol. 

Multiple human clinical studies have also shown that DHEA effectively treats depression:

1. The National Institute of Mental Health studied 46 patients age 40-65 with major and minor depression. After six weeks of administering DHEA, 23 patients showed a 50% reduction in depressive symptoms. Ten patients chose to continue taking DHEA for one year at a low dose and remained free of depression.

2. Ten elderly men (58-69 years old) with a range of age-related symptoms such as feeling weak and having low-energy showed significant improvement in symptoms after taking 25 mg of DHEA every morning for one-year. 

3. In a 1999 study published in Biological Psychiatry, researchers tested the effects of DHEA in 15 people who had developed mid-life depression. Sixty percent of those receiving DHEA responded well to treatment compared to only twenty percent of those who received the placebo.

4. In a large-scale study conducted in 2007, of 2,855 elderly men and women, it was concluded that low DHEAS levels were linked with depressive symptoms.

5. A 2007 study of sixty-one patients with Dysthymic disorder (DD), a chronic state of mild depressive symptoms, found that individuals with DD have low levels of DHEAS.

A  2009 comprehensive review of DHEA in the treatment of depression concluded:

"... to date, every controlled trial of DHEA in depression has reported significant antidepressant effects."

Managing cortisol is becoming a major factor in the treatment of stress and its resulting depression.  There is more research to be done, but to be honest, no matter where one looks, there is always more research that needs to be done.  The results from the above list of studies is already more impressive than the results of traditionally approved drug treatments for depression.

Does this mean you should run out and supplement with DHEA without guidance from a health care provider?  No.  DHEA is a hormone, not a vitamin.  But the clinical results show that this treatment will help some of those not helped by their current anti-depressant medications.

In our next post we will be discussing Brain Derived Neurotrophic Factor …

Stay Tuned!

Yours,

David