If this were true, wouldn't we expect depression not to recurr after
termination of a thorough anti-depressant medication treatment? The data
seem to show otherwise.
Bill Scott
>>> Carol DeVolder 07/24/11 12:45 PM >>>
This is kind of a long post, and many of you will not be interested
in it at all (maybe nobody), but this is in response to the discussion
of antidepressants, depression, its potential causes, and so on. I'm not
turning it in for a grade, so please don't grade me on it. I hope it is
somewhat coherent though, because I really like all of the possibilities
for explanation that emerge in this model. In a previous post, I
mentioned Robert Julien’s Behavioral Pharmacology as an
excellentresource. Of course I don’t think he has the final word on the
topic ofdepression and antidepressants, I do think he provides valuable
insight.Paraphrasing what he has to say on the topic (paraphrasing
liberally, I mightadd, so don’t fault me for plagiarism*I already know
that I am doing that),starting with the pathophysiology of depression,
Julien describes what herefers to as the neurogenic theory of
depression.
This description describes depression as related to loss ofvolume (due
to neuron loss), especially in the hippocampus. Julien points out that
numerous symptoms ofdepression such as impaired attention,
concentration, and memory are related tofunctions of the hippocampus or
the prefrontal cortex. He also notes thatchemicals such as cortisol can
have deleterious effects on the functioning ofthe hippocampus and
prefrontal cortex(tying together the research that suggeststhat stress
can result in loss of brain volume, especially in these areas).According
to research by Frodl et al. (2007), the hippocampus actually shrinkswhen
exposed to a variety of stressors, including depression. That same
researchreports that stress is one of the most common causes of
depression.
However, Julien notes that recent research has shown thatexisting
neurons are able to repair or remodel themselves (plasticity), and
infact neurogenesis also is possible; again, especially in the
hippocampus, butalso in the prefrontal cortex. According to his
explanation, two known secondmessenger neurochemicals are importantin
protecting neurons from damage due to trauma or injury, and in promoting
andmaintaining the health and stability of newly generated neurons.
Julien arguesthat antidepressants increase the action of these 2nd
messengersystems resulting in repair and restoration of volume to the
hippocampus andpossibly the prefrontal cortex.
Here’s a stepwise summary of how these 2ndmessengers might act in the
presence of SSRIs /SNRIs or other antidepressants:
Step 1: Antidepressantdrugs increase the level of the monoamines
(especially 5-HT and NE) in thesynapse.
Step 2: binding ofeither 5-HT or NE triggers a 2nd messenger system
that uses cAMP (cyclicAMP).
Step 3: cAMP triggersthe expression of CREB (cAMP
response-element-binding protein).
Step 4: CREB activatesthe production of BDNF (brain-derived
neurotrophic factor)
Step 5: BDNF promoteshealthy neurons and connections (likely involving
the growth of new neurons,especially in the hippocampus).
Julien supplies ample references to support these statements.Also,
Julien writes that the time frame in which all of these steps occur
mightexplain the therapeutic lag that accompanies the onset of
administration ofantidepressants and the onset of their therapeutic
effect.
If you’ve read this far, hopefully I’ve shown thepossibility that
depression may be due to stress (loss of a loved one, jobloss, ongoing
factors), chemical imbalance (genetic or acquired), or theinteraction of
any or all of these factors (the diathesis-stress model).
Althoughantidepressants may alleviate depression under this model, other
things can aswell; for example, psychotherapy, exercise, self-help,
stress-reductiontechniques, or time.
Some references:
Angelucci, F., et al. (2005). BDNF in schizophrenia, depression,
andcorresponding animal models. Molecular Psychiatry 10, 345-352.
Blendy, J. A. (2006). The role of CREB in depression andAntidepressant
treatments. Biological Psychiatry,59, 1144-1150.
Duman R. S. and Monteggia, L. M. (2006). A neurotrophicmodel for
stress-related mood disorders. Biological Psychiatry, 59 , 1116-1127.
Frodl, T. et al. (2007). Association of the brain-derivedneurotrophic
factor Val66Met Polymorphism with reducedhippocampal volumes in major
depression. Archivesof General Psychiatry, 64, 410-416.
Nair, A., and Vaidya, V. A. (2006). CyclicAMP responseelement binding
protein and brain-derived neurotrophicfactor: Molecules that modulate
our mood? Journalof Bioscience, 31, 423-434.
Done for the day--going outside as soon as it stops raining.
Carol
--
Carol DeVolder, Ph.D.
Professor of Psychology
St. Ambrose University
518 West Locust Street
Davenport, Iowa 52803
563-333-6482
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