The Biology of Stress and Depression Pt. 6: The Cholesterol/Dopamine Connection

(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 sixth installment on the biology of stress and depression turns to research on cholesterol and its relationship to emotional states. For some people, the information presented here may come as a bit of a shock.  There are strong indications in current research that cholesterol has very little to do with heart disease. There have been several books written on this problem that go into great detail. My own work can be found here (click link). The footnotes nested in the text are particularly valuable to anyone researching the subject.

In short, cholesterol by itself is not bad for your health. Cholesterol is involved in basically every process in the body given that various parts of individual cells are made up of cholesterol.  Given the amount of research available, this post is not going to spend much time defending the position that cholesterol is helpful and not harmful. It is, however, going to explain the vital role that cholesterol plays in your emotional stability.

Several years ago, there was a paper published in the Journal of Psychiatric Research.  The research followed just shy of 4, 500 veterans for 15 years. At the end of the study they made an in interesting finding that participants with LOW total cholesterol numbers who concurrently were suffering from depression were SEVEN TIMES more likely than other subjects to die prematurely from unnatural causes such as suicide and accidents! This work basically got no attention from the media. Most medical doctors were likely to dismiss the study as well. Why? (A closer look at this WHY question can be found by following the link above)

For years scientific research has noted the problematic relationships between low cholesterol, depression, and an elevation in problems with impulsive behaviors. For example:

1.       A study published in the Journal of Behavioural Medicine observing men aged 40 to 70 found that the men with long-term, low total cholesterol levels "have a higher prevalence of depressive symptoms" when compared to subjects with higher cholesterol levels.

2.       A 1993 study in the prestigious journal The Lancet reported, "Among men aged 70 years and older, categorically defined depression was three times more common in the group with low total plasma cholesterol...than in those with higher concentrations..."

3.       Women with low cholesterol levels are also vulnerable to depression. A Swedish study, also published in the Journal of Behavioural Science, involving 300 healthy women, aged 31 to 65, concluded that women in the lowest cholesterol group, the bottom ten percent, suffered from significantly more depression symptoms than the other women in the study.

Unfortunately, a diagnosis of depression is often associated with a higher risk of suicide. The link between suicide and low cholesterol is also well supported

1.       The results of a 2008 study of hospitalized psychiatric patients published in the journal of clinical psychiatry suggested that low cholesterol may be associated with suicide attempts.

2.       University of Minnesota from the Archives of Internal Medicine found that people with total cholesterol levels lower than 160 mg/dL were more likely to commit suicide than those with higher cholesterol levels.

3.       As published in Progress in Neuro-Psychopharmacology and Biological Psychiatry, cholesterol and blood fat levels were found to be lower, on average, among patients with bipolar disorder who had attempted suicide than bipolar patients who had not.

 So, where is the connection between depression and low levels of cholesterol? Research from the Karolinska Institute has found that a healthy dose of oxidised cholesterol (known as oxysterol) is indispensable in promoting the development of the human stem cells that make dopamine. For those who don’t know, dopamine is a big player in the chemistry of our nervous systems. A huge variety of illnesses are associated with upsets in dopamine levels.

People with Parkinson’s disease experience the death of the dopamine producing neurons in the substantia nigra regions of the brain and this leads to general shaking in their bodies. People with ADHD, (Attention Deficit Hyperactivity Disorder), strive unsuccessfuly to supply their brain with enough dopamine to focus. One of dopamine's functions is to kick start us. It is a kind of chemical motivator. It is actually small bursts of dopamine that make us want to actually get up and DO stuff. 

Our brains are big on cholesterol! It is a primary building block of our brain cells and without it they literally die off. But in addition, as this article emphasizes, cholesterol is a primary contributor to the production of dopamine and dopamine is what makes us motivated and forward thinking. Dopamine is the currency of the reward center in our brains.

We usually think of dopamine as linked more with things like reward or drug-addiction, but the list of things dopamine actually does is more complex than that. Dopamine is involved in movement, for example, but it is also involved in, for lack of a better word, “motivated behavior”. Think of dopamine in terms of “salience”. In other words, it helps to determine how relevant something is to your interests. Its effects encompass all motivated behaviors for things such as food, sex, drugs, etc. as well as the development of major depressive disorder. People with depression often exhibit reduced motivation, anhedonia (a decrease in pleasure from usually enjoyed things), as well as possible decreases in motor function.  

All of these difficulties can be linked to incorrect levels of dopamine. So targeting the dopamine system is one of the ways in which we can look at potential mechanisms and treatments for depressive behaviors.

Cholesterol is also the precursor to the neurosteroids we discussed in previous postings (DHEA & Pregnenolone). Low cholesterol means low output of those vital sparks that keep our nerves happy and active.

The research noted in this and previous posts suggests strongly that cholesterol is incredibly important in the stability of mental health. It is a key to the production of dopamine. Dopamine is central to bodily movement & “wanting things” like: new experiences, new possessions, new potential mates and a future. All of this begs the question of whether knee jerk use of medications and alterations in diet designed to decrease cholesterol levels are actually a wise idea.