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 excellent resource. Of course I don’t think he has the final word on the topic of depression and antidepressants, I do think he provides valuable insight. Paraphrasing what he has to say on the topic (paraphrasing liberally, I might add, so don’t fault me for plagiarism—I already know that I am doing that), starting with the pathophysiology of depression, Julien describes what he refers to as the neurogenic theory of depression.
This description describes depression as related to loss of volume (due to neuron loss), especially in the hippocampus. Julien points out that numerous symptoms of depression such as impaired attention, concentration, and memory are related to functions of the hippocampus or the prefrontal cortex. He also notes that chemicals such as cortisol can have deleterious effects on the functioning of the hippocampus and prefrontal cortex(tying together the research that suggests that stress can result in loss of brain volume, especially in these areas). According to research by Frodl et al. (2007), the hippocampus actually shrinks when exposed to a variety of stressors, including depression. That same research reports that stress is one of the most common causes of depression. However, Julien notes that recent research has shown that existing neurons are able to repair or remodel themselves (plasticity), and in fact neurogenesis also is possible; again, especially in the hippocampus, but also in the prefrontal cortex. According to his explanation, two known second messenger neurochemicals are important in protecting neurons from damage due to trauma or injury, and in promoting and maintaining the health and stability of newly generated neurons. Julien argues that antidepressants increase the action of these 2nd messenger systems resulting in repair and restoration of volume to the hippocampus and possibly the prefrontal cortex. Here’s a stepwise summary of how these 2nd messengers might act in the presence of SSRIs /SNRIs or other antidepressants: Step 1: Antidepressant drugs increase the level of the monoamines (especially 5-HT and NE) in the synapse. Step 2: binding of either 5-HT or NE triggers a 2nd messenger system that uses cAMP (cyclicAMP). Step 3: cAMP triggers the expression of CREB (cAMP response-element-binding protein). Step 4: CREB activates the production of BDNF (brain-derived neurotrophic factor) Step 5: BDNF promotes healthy 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 might explain the therapeutic lag that accompanies the onset of administration of antidepressants and the onset of their therapeutic effect. If you’ve read this far, hopefully I’ve shown the possibility that depression may be due to stress (loss of a loved one, job loss, ongoing factors), chemical imbalance (genetic or acquired), or the interaction of any or all of these factors (the diathesis-stress model). Although antidepressants may alleviate depression under this model, other things can as well; for example, psychotherapy, exercise, self-help, stress-reduction techniques, or time. Some references: Angelucci, F., et al. (2005). BDNF in schizophrenia, depression, and corresponding animal models. *Molecular Psychiatry* 10, 345-352. Blendy, J. A. (2006). The role of CREB in depression and Antidepressant treatments. *Biological Psychiatry, 59,* 1144-1150. Duman R. S. and Monteggia, L. M. (2006). A neurotrophic model for stress-related mood disorders. *Biological Psychiatry, 59* , 1116-1127. Frodl, T. et al. (2007). Association of the brain-derived neurotrophic factor Val66Met Polymorphism with reduced hippocampal volumes in major depression. *Archives of General Psychiatry, 64*, 410-416. Nair, A., and Vaidya, V. A. (2006). CyclicAMP response element binding protein and brain-derived neurotrophic factor: Molecules that modulate our mood? *Journal of 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 This e-mail is probably not confidential, but please don't share it without asking. --- You are currently subscribed to tips as: [email protected]. To unsubscribe click here: http://fsulist.frostburg.edu/u?id=13090.68da6e6e5325aa33287ff385b70df5d5&n=T&l=tips&o=11592 or send a blank email to leave-11592-13090.68da6e6e5325aa33287ff385b70df...@fsulist.frostburg.edu
