February 09, 2010
 
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The Neurobiology of Depression
 
Dr. Lopez is a faculty member of the Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor.


Being clinically depressed is very different from just feeling down or blue. Depressive episodes (there are several kinds) can last months, sometimes years, and can interfere with your social and work functioning. Unfortunately, depressive episodes also tend to recur and, if left untreated, will become more frequent and/or more severe as the disease progresses.(41)

According to the official professional reference guide, Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), to be considered depressed, you have at least five of the following symptoms and they represent a change in your life:
  1. Depressed mood most of the day, nearly every day
  2. Markedly diminished interest or pleasure in all, or almost all, activities
  3. Significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day
  4. Insomnia or sleeping too much (hypersomnia) nearly every day
  5. Psychomotor agitation or retardation nearly every day
  6. Fatigue or loss of energy nearly every day
  7. Feelings of worthlessness or excessive or inappropriate guilt
  8. Diminished ability to think or concentrate, or indecisiveness
  9. Recurrent thoughts of death, recurrent suicidal ideation, or a suicide attempt or a specific plan for committing suicide
All Too Common
Depression is very common. Seventeen per cent of people will experience depression sometime during their life. To add insult to injury, if you are acutely or chronically ill, you are even more likely to suffer from it, with rates ranging from 30% to 50%, depending on your specific medical condition.

Though the picture sounds grim, (and will seem especially so if you are depressed, for thinking nothing will get better is often a symptom of depression) we are starting to learn more about the biochemical and other factors that may be involved. Hopefully, with this knowledge, will, eventually, come effective treatment strategies.

Do We Know What Causes Depression?
The actual basis of depression is unknown but it is widely accepted that it is influenced by genetic, environmental and neurobiological factors. Depression does run in families26 but whether this is genetic or simply reflects the kind of parenting a depressed person is able to offer their child is difficult to determine. In addition there are many environmental factors, such as loss of a loved one, unemployment, an unexpected medical illness, that appear to increase the likelihood of depression.

Many brain chemicals ("neurochemicals") and hormones have been linked to the development of depression (e.g., norepinephrine, dopamine, thyroid hormones). However, research studies have implicated disturbances in the serotonin (5-HT) system and the Limbic Hypothalamic-Pituitary-Adrenal (LHPA) axis as two of the neurobiological alterations most consistently associated with mood-altering illness.(18)(36)(24)(39) Recent work, in fact, has strongly suggested that the interaction between these two biochemical systems may play a significant role.

Adrenal glucocorticoid (the "stress" hormone), which helps regulate your metabolism and is produced by the adrenal gland, a tiny gland that sits on top of the kidneys, interacts with serotonin 5-HT receptors in the brain during conditions of chronic stress or severe allostatic load." This is not surprising, as we have known from studies on animals that the two systems are linked in a variety of ways.(33)(7)(30) One of these linked regions, the limbic HPA axis (LHPA), regulates arousal, sleep, appetite and the capacity to experience and enjoy pleasure, as well as the control of mood. As the list of symptoms at the beginning of this article indicates, the functioning of each of these areas can be disturbed in a depressive episode.

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