The Brain Chemistry of Depression -- Stress Hormones

If changes inside the cell are the basis for depression symptoms, what leads to such changes?  In other words, what might be the first event leading to depression?  

A new theory is emerging that probably answers this question for at least some versions of depression, especially in people who have suffered some kind of emotional trauma, especially those who suffer that trauma early in their life.  

Unfortunately, early life trauma is surprisingly common, particularly sexual abuse of young women.  Dr. Sadek (below) cites a million sexual abuse cases per year in the U.S., "verified". If you doubt that, read the abstract from Sweden reporting a minimum estimate -- but  don't read this abstract if you already know about the subject all too well.  

The new theory goes beyond serotonin and norepinephrine, which are clearly involved in depression, to look at stress hormones.  Many people with mood problems have others in their family who also have mood problems; the same is true of anxiety problems.  So one of the factors leading to depression is a genetic vulnerability, although not in all cases.  The other factor is some early traumatic experience.  Sexual or physical abuse is one example.  So is early separation from, or neglect by, a nurturing parent.  So is prolonged exposure to emotional abuse (very harsh emotional treatment, intended to hurt -- for one definition).   These factors -- especially when combined -- lead to changes in a person's nervous system that appear to be very long-lasting, perhaps lifelong in many cases.  Stress hormones within the brain may be the basis for these lasting changes. 

Here is a brief summary of how depression is being thought to begin.  This is merely my attempt to translate into "plain english" the summary offered by the main researchers in this area -- Dr. Nemeroff and colleagues, and Dr. Sapolsky.  I'll give you the references in a minute if you want to try the "doctor lingo" version. 

The general "new" idea is that stress hormones may actually damage the brain when stress is sustained.  Low doses of stress may cause changes that are useful, but if this goes on too long, those changes can start to become harmful.  What starts out as some minor remodeling, like re-doing your bathroom, can become actual destruction, like damaging the walls and getting water damage in three rooms when all you meant to do was move the bathtub!

Much of the new research focuses on a stress-related molecule called "corticotropin releasing factor (CRF)".  Until recently CRF was thought to be the signal from the hypothalamus (the "master gland") to the pituitary (traffic light central for the brain hormone system), telling it to release ACTH, which in turn tells the adrenal cortex to release adrenalin (epinephrine).  If I just lost you, don't go away yet.  That was the basic model of the stress reaction from the brain on down.   You don't need that part of the model to see what's new and important here. 

It turns out that several sites in the brain make and release CRF.  That changes the whole model, see?  CRF is no longer just some measly messenger starting the message from the brain to the body, it is a central and common molecule in the entire stress response within the brain -- that is, before the rest of the body gets in the act via adrenalin.  And unfortunately, it looks like stress can do bad things to the brain (perhaps via CRF itself).  The hippocampus, especially, seems to be vulnerable in two ways: first, stress may just shrink the hippocampus directly, probably by promoting cell death there.  This is the subject of the lengthy review by Dr. Sapolsky.  The mechanism may include  interfering with the cell-feeding ("trophic") local molecules that may be important in preventing depression in the first place.  

 To go beyond this brief summary, you can read an on-line version from the researchers themselves, if your doctor vocabulary is very good.  Here's a medical dictionary if you need one.  To read Drs. Sadek and Nemeroff, you'll need to register first on Medscape if you've not done so already (free, no spam).  








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