Stress, Cortisol, and Depression

What’s the evidence to think there’s a link between stress and depression?

There are 23,000 references in PubMed if you type in stress and depression.

The first type of evidence is epidemiological: People who have just had major stressful events are statistically more likely to fall into a depression.

Stressors are 2.5 times more likely in depressed patients compared to controls.

In community samples, 80% of depressed cases were preceded by major life events

Most episodes of major depression are preceded by stressful life events (although
most people do not become depressed even if they experience a negative life event).

It all seems so obvious that stress could lead people to be depressed. But actually it’s not.

For example, why doesn’t excessive stress cause something else? Why doesn’t it cause us to run amok, doing all sorts of wild and crazy things? Why depression?

Why doesn’t stress cause us to work harder? That would be logical–for our bodies to pump out more adrenalin and make us work harder to fix the problems we face.

The answer is we don’t know.

But to have any chance of understanding the human stress response and depression, we have to start with the basic nature of the human stress response.

We have a generalized response to a variety of stresses. Psychological stress and physical stress on the body generally lead to the same set of hormonal responses within the body, which is in itself unusual, or at least, counterintuitive.

We have one main stress response syndrome in our body:
Perception of threat
Hypothalamus activation
Pituitary activation
Adrenal gland activation
Adrenalin+Noradrenalin+Cortisol

During stress, a chain reaction of physical and chemical processes prepares the body for a fight or flight situation. After the logical, thinking part of the brain recognizes that danger is present, another part of the brain, the hypothalamus releases Corticotropin Hormone Releasing Factor (CRF). This in turn stimulates the pituitary (the “master gland”) to release Adrenocorticotrophic Hormone (ACTH). The release of ACTH triggers the secretion of cortisol from the adrenal cortex (the adrenals are located on the kidneys) to provide energy and to help suppress inflammation. Through a neural pathway (that is, via a nerve rather than chemical release in the blood stream), the adrenals are also stimulated to produce more chemicals called adrenaline and noradrenaline. These in turn serve to accelerate the pulse rate, elevate blood pressure, and stimulate the central nervous system.

The fight or flight response is a good thing. It has saved many of our forbears from saber tooth tigers and other dangers. But what is good for us in the short run is not necessarily good for us in the long run.

And cortisol is one of those things. I believe that our best bet at the current time to understand why stress would lead to depression is cortisol.

We do have some evidence that that may be true.

Cortisol like drugs, i.e., steroids, can cause depression as one of their side effects.
People who are given high levels of synthetic glucocorticoids for autoimmune disorders or inflammatory issues have greatly increased risk of going into a depression.

Secondly, we know that long term exposure to cortisol results in some really nasty effects on the brain, particularly the hippocampus. The hippocampus is the memory center of the brain. It also does something else. It modulates the release of cortisol. Long term exposure of the hippocampus to stress leads to loss of neural branches called dendrites. And it leads to problems with memory loss.

If cortisol has a damaging effect on the hippocampus, then it also might have a damaging effect on other parts of the brain. There is only one article I found on this , but it could be true. The negative effects of prolonged cortisol exposure occur throughout the body, so it is not a far stretch to believe that we have only begun to understand the negative effects of it on the brain.

Thirdly, about 50% of people with depression hypersecrete cortisol. Of course, by itself this proves nothing. But it would be consistent with the hypothesis that too much cortisol leads to – too much cortisol. In other words, stress leads to too much cortisol, which can lead to damage of the hippocampus, which unleashes more cortisol.

By the way, elevated cortisol levels occur in mania as well as depression.

Now, let’s transition from looking at depression as a biological disorder to looking at the psychological aspects of depression.

It is certainly possible that once we become depressed, the depression itself stresses us. It enhances our negative thoughts, which increase our perception of threat and stress, which increases our cortisol output, which in turn would further cause disorder of brain functioning.

There is some evidence that the anterior cingulate, a curved bundle of nerves around the corpus callosum between the limbic system and the prefrontal cortex is affected by or is causing depression. And there is a small amount of evidence that high cortisol levels can cause atrophy or smaller volume in the anterior cingulate.

And there, the physiological trail runs cold. We just don’t know the rest. But sometimes a bad theory is better than no theory at all.

So here is the theory in my head when I am working with patients.

Stress begins for most people as a psychological process, although there are also physical components. If my wife is in the hospital, I may sleep different hours, eat different meals, and so on. But also there is mainly psychological stress.

Then the HPA axis causes the release of cortisol. If this is on a sustained basis, the long term effects of cortisol affect the hippocampus and perhaps the anterior cingulate.

Since the hippocampus is supposed to help regulate the HPA axis, if it is impaired, then the HPA axis may get further out of control leading to more cortisol.

Ultimately, the anterior cingulate and the serotonin pathways are affected, leading the person to become depressed if this goes on for too long, and the person has certain genetics.

But even if the trail runs cold, we may know enough to inform our decision making. Stress, particularly prolonged and severe stress is not our friend. Combatting stress takes time and energy, and in some ways it is simply easier to let ourselves be stressed out, even if that is more painful. But it is not good for our brains and it is not good for us. And depending on our genetics, it is often a luxury that we just can’t afford.

Thinking about stress psychologically.

Stress is not just the result of a situation. It is the combination of the situation and our way of perceiving the situation.

We used to think of, or I used to think of, stress as something which could go away. And once it went away, then everything would return back to normal. This way of thinking clearly has gone out the window. Memory will sometimes return back to normal after exposure to chronic stress is over, but not always.

And multiple depressions leave us even more vulnerable to further depressions. Thus, we cannot conclude that we simply return back to normal.

I sometimes say to my patients that stress is a luxury that we can’t afford. What do I mean by that? Because oftentimes, there is little that we can do about stress. Either we are stressed or we aren’t.

But that’s not quite true. There are things we can do about stress.

Cognitive therapy, for example, is aimed at helping people to be less stressed by situations than they otherwise would be.

So there is some sense in saying that stress is a luxury that we can’t afford. To the degree that we do have any control at all over our stress, we cannot afford to let ourselves sink to the bottom of the pit, with the idea that we will eventually bounce out. For some of us, this undoubtedly triggers a genetic response of biological depression. For others of us, it may impair our hippocampus if this goes on for months or years. And for others of us, it may do both.

So if stress is a luxury that we cannot afford, what can we do about it?

This is where the panoply of typical depressive therapies comes in.

Cognitive therapy works to reduce irrational negative thoughts. Why is this important? Because without excessive negative thinking, our body just might turn off the stress response. Which could turn off the cortisol. Which would give our brains a chance to heal.

Behavior therapy sometimes works on assertiveness training. Why is this important? Because assertiveness often fixes situations that we perceive as threatening, which means we don’t have to be stressed, which means that our bodies can turn off the cortisol, which lets our brains heal.

Interpersonal therapy works on improving interpersonal relationships. Which again often fixes situations that we perceive as threatening, which means we don’t have to be stressed, which means that our bodies can turn off the cortisol, which lets our brains heal.

Therapy sometimes helps the person to gain control, or at least enhance their feeling of control, which etc etc.

Get the picture? We cannot afford the luxury of stress. If there is anything that we can do which can turn off the stress response, then we need to do it. If we can divert our attention for a few hours, so much the better. If we can fix the situation, so much the better. If we can find more adaptive ways of thinking about the problem so much the better.

Can People Keep Up Psychologically in a Flat World?

The recent book, The World is Flat, offers many stimulating ideas about how the world has evolved in recent years to the poker game it now is--the U.S., China, India, and the other players at the table. It gives a synopsis of the recent past but also a glimpse of the future. For people who have not yet read it, it summarizes the how the computer age has led us into a new economic age in human history.

For the first time, a person in India without an education in a first world country, can compete on almost a level playing field with people in first world countries. In the past, it might be necessary for a person from China who wanted to be successful in business, to train at Harvard or UCLA, and then to remain in the United States or Europe to establish a business. As new businesses become more computerized and more dependent on the internet, the actual geographic location of the business and entrepreneur becomes less and less important. It is becoming less important to do business physically in a first world country. Moreover, there can be a benefit to establishing the location of a business in a third world country if that is where the cheap labor is and if that's where the resources are. Sales and marketing can to a great degree be done over the internet while the physical plant is almost anywhere in the world.

The pace of change is staggering. China is turning out 65,000 engineers a year. In the United States, we are no longer just competing with others in the U.S. We are competing with China, and India, and soon others as well. We have been setting the pace for them to keep up with; soon they may be setting the pace. We have been content (many of us) to work 8 hour days. They are willing to work 12 hour days to be in the game. Can we keep up with them? Do we even want to keep up with them? Can we afford not to keep up with them? And if we do, can we deal psychologically with the continuing changes which will be at our doorstep. For persons in the computer industry, skills start to become obsolete after a year or so of not keeping up. But in the future, it could be six months, and then even less time.

In the past, individuals in the U.S. could decide whether they wanted to be ambitious or not. Whether to work hard or not. Whether to strive for more money, possessions, etc.--or not. And we can still make that choice. However, individual choices now have national implications and repurcussions, perhaps in the same way that they did during World War II. During that war, individual productivity was tied to the survival of the nation. The United States could not thrive and perhaps not even survive if people were to choose the easy life.

But whereas that war was limited to a particular period of time, there is no end in sight to the international competition which is only now gearing up to a full degree. Countries who fall behind, may stay behind for a long time. Countries who choose a life of leisure may end up being the servants of the trendsetters, that is, economically doing the bidding of those with the patents, the copyrights, and the industries.

In a worst case scenario there might be a frenetic pace of competition in which there was no pause. This is the most troubling aspect of the coming situation psychologically. People need balance in their lives. They need some leisure. They need time to reflect. A state of urgency (if not emergency) could be imposed theoretically, not this time by a dictator or the need to respond to a dictator as in World War II, but by the simple need not to be left behind, not to become a satellite nation to other more industrious nations which were willing to do whatever it took to be the inventors, the producers, and hence the dominators of the world economy.

This is reminiscent of the Charlie Chaplin movie, Modern Times, in which the machine conveyor belt gets the best of him . He cannot stop it. Once the machine is started, it seems unstoppable. In contrast to his movie The Great Dictator, it is now the machines (and those who run it) which are in control. Is it possible that the nations of the world could, in their competition to survive and flourish, get onto a treadmill in the world where no nation can afford to pause or get off? Is it possible that no one would dare to get off? And how might this translate down to the level of the individual? Could individuals get caught up in this same frenetic pace? What of the people who cannot deal with that new pace? It is not only cultures but also individuals which must adapt to it.

But perhaps this is looking at the situation somewhat pessimistically, from the vantage point of one living in America, where comfortable living is now rather taken for granted. It can be daunting facing the new crop of 65,000 engineers a year coming from China. But for one of those graduating students, the internet revolution flattening the Earth is indeed an opportunity to break free of poverty and isolation.

The long term consequences cannot be foreseen. But we can keep our eyes open to both the potential rewards and the dangers of the new and accelerating pace of global competition.

Stress and Anger as Psychological "Luxuries" We Can't Afford

Most people think of stress and anger as simply part of life. We have to put up with them because they come with the territory of living. However, research increasingly indicates that both of these take a negative toll on our minds, bodies, and relationships.

Certainly, they are not totally avoidable. Some degree of stress is healthy for the body and mind. It actually strengthens us. But the old saying of Nietzche is not true--"Whatever does not kill me makes me stronger." In fact, what does not kill us may kill off brain cells and add fat to our waist. Excessive stress has been shown to harm cells in the hippocampus, which is a part of the brain central to storing memories. It has also been shown to lower the immune system's ability to fight off infection. Depression and anxiety can be triggered by stress in some individuals. For others, stress may lead to unhealthy use of alcohol and other substances.

The goal of the healthy individual need not be to eliminate stress altogether but to avoid very high, unusual levels of stress if possible. How can this be done? Many people believe that the stress they experience is totally beyond their control. But it is not. Here are some things which can be done to diminish stress.

First, live a healthy lifestyle. Do the obvious. That is, don't take excessive risks financially. Nurture and nourish relationships. Build for the future in both finances and social support.

Secondly, work on any excessive negative thinking. My web site has several handouts on how to do this (http://www.drbeckham.com/). Very often 50% or more of the stress we experience is of our own making from excessive negative thinking.

Deal with problems slowly, methodically, one at a time. Don't avoid problems. They will just pile up. And don't try to take on all problems at once. That will just overwhelm you.
Most of my clients have one of two different problems: either excessive negative thinking or avoiding problems. Working these two areas can do wonders for a person's stress level.

Next week: the "luxury" of anger.