Thank you for writing! The treatment of depression is a very complex subject, but I think it is possible to give you some basic facts in a short article. Please keep in mind that some of the discussion in this article is very simplified to keep the article short.

The problem with the word "depression" is that it can stand for anything from a bad hair day to a very serious or life-threatening disorder. So, professionals like me don't use the word depression without adding to it the word "mild," "moderate," or "severe."

Depressions that last longer than two weeks and include symptoms such as early morning awakening with difficulty returning to sleep, significant loss of motivation, low energy, loss of interest in life (suicidal feelings or plans, constant sadness), and loss of appetite with weight loss are the moderate to severe type and do not generally get better without help from medication. Milder forms of depression may include symptoms such as increased hostility, irritability, over-eating, over-sleeping, and difficulty concentrating. "Burnout" is a term that has been used for depression that is induced, for instance, by over-working. "Clinical depression" is a term that is reserved for the moderate to severe forms of depression. Burnout and clinical depression can be very similar and arise from the same sources of stress.

No matter how healthy our brain may be, we are each vulnerable to a more biologically-based depression under the right circumstances of physical or emotional stress. How vulnerable we are to depression depends on our physical ailments and our family history of depression. More ailments and more family members with clinical depression signify a higher vulnerability.

To understand which depression treatment strategy to utilize, it is important to understand how stress produces depression. After reading this article, you will be able to impress your friends with words like hippocampus, corticotropin releasing factor (CRF), and brain-derived neurotrophic factor (BDNF). CRF appears to be the main culprit in depression. Stress dramatically increases CRF levels in the brain. CRF is essentially toxic to nerve cells in the hippocampus.

The hippocampus is a small part of the human brain located inside each of two temporal lobes. It forms a part of the limbic system. Among other things, it is involved in happiness, short-term memory, navigation, and information routing. It is one of the "oldest" parts of the brain. Unlike the cerebral cortex, that huge, "newer" part of the brain that makes humans the thinking animals that we are, the hippocampus exists in almost all mammals, in a similar form and having a similar function as it does in humans.

By using special brain MRI imaging techniques, many human studies have found a link between a smaller hippocampus and moderate to severe depression. What makes a hippocampus smaller? The current answer is that high CRF levels damage the hippocampus which makes it shrink. You might wonder how people who are always stressed avoid hippocampus damage and a resultant clinical depression. That is where BDNF comes in. In my opinion, I think we will discover that an individual's baseline BDNF level is genetically determined.

BDNF is made by nerve cells and not only is it a protective chemical, it also stimulates neurons to grow and make more connections to other neurons. The hippocampus normally has large amounts of BDNF. So, the cycle goes like this: Stress increases CRF; high CRF levels damage the hippocampus; damaged nerve cells lose the ability to produce certain chemicals such as serotonin and BDNF; depression follows.

Is there anything that can help? In rats, both the antidepressant Prozac (a selective serotonin reuptake inhibitor or SSRI) and exercise increase BDNF levels. In rats, both Prozac and exercise also protect against the bad effects of CRF. In rats, Prozac helps the hippocampus regenerate new nerve cells and dendrites. No tool yet exists to measure BDNF in the human hippocampus. However, given what we know about human CRF levels and stress, the relationship between a smaller hippocampus and depression, and how SSRI antidepressants actually help the hippocampus recover, we can be reasonably sure that CRF is bad and BDNF is good. If you wish to read more about the hippocampus, please visit www.hippocampus.us.

It is very difficult to live a stress-free life. Before there were medications that increased central nervous system chemicals such as norepinephrine, serotonin, and dopamine, moderate to severe depression was often treated primarily by taking a long vacation at a local "sanitarium." By decreasing the stress levels over a long period of time, it was likely possible for the hippocampus to recover without medication. However, this is generally not a treatment available or even preferable for most people. SSRI antidepressants do the work of assisting the hippocampus in the healing process. For moderate to severe depression, an appropriate antidepressant medication is a very important part of the treatment strategy.

However, for mild to moderate depression, there is no single, best treatment. In my opinion, medication is often not a complete solution. In fact, in the mild to moderate range of depression, medication can be a complicating factor by producing mostly side-effects.

Mild to moderate depression is complex for many reasons. It is very individual. Many difficult experiences and dysfunctional belief systems can give rise to depression. That is why, for the purpose of finding long-lasting solutions to depression, professionals should not rush to judgment and think only of one-sided solutions. Utilizing compassionate and thorough data gathering and assessment is important for discovering the psychological roots to a nagging depression and to formulate a plan of treatment.

Many professionals feel that it is not necessarily what happens to depressed persons that causes them to be depressed, but rather, what they tell themselves about what happens. Some examples of common thinking patterns that can lead to depression include over-generalized thinking, perfectionistic thinking, and the tendency to catastrophize.

Social skills that should be looked at are related to dissatisfaction with friends, coworkers, family, or job. Depression can result from a feeling of disconnectedness brought about by misperceptions of ourselves and others. Depressed individuals often have negative self-perceptions. There may be a tendency to be less assertive and less positive for various reasons relating to self-concept or old programming about how one should behave or what to expect out of life.

In my opinion, psychotherapy, notably cognitive–behavioral or interpersonal psychotherapy, should be considered the treatment of first choice for mild to moderate depression because it has been shown to lead to a superior long-term outcome. If antidepressants are used, psychotherapy should be included because of what has been shown to be a higher risk for relapse with treatment by medication alone. In addition, it has clearly been shown that exercise increases BDNF and cell proliferation in the hippocampus.

If therapists can learn to be patient in dealing with the emotional difficulties of depressed individuals and help them to find specific treatment strategies, a very significant percentage will have positive outcomes. I hope this helps. -- Best wishes, Dr. Debug.

Ron Sterling, M.D. (Dr. Debug) is an award-winning psychiatrist in Seattle, Washington. He has been writing for newspapers and magazines since 1998 on subjects ranging from good manners to senior mental health. He hosts and maintains the well-known Internet mental health center, DearShrink.com. The Doctor Debug column is dedicated to assisting with the "debugging of malfunctioning elements in our own personal programming."

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