Depression

Neurogenesis and Depression

To this point there are confounding findings as to the role of neurogenesis and depression using animal models of depression.  Originally it was thought that a lack of neurogenesis may be the cause of depression due to the correlation between patients showing depression like behaviors and a decrease in the size of those patients’ hippocampus. However, further studies showed evidence to dispute this and new theories were formed from studies done using antidepressants.  These studies showed that neurogenesis was less involved in becoming depressed, and more involved in the treatment.  Mainly focusing on SSRI’s and tricyclic antidepressants, theories were formed to how the mechanisms of these antidepressant drugs used neurogenesis to help deter the symptoms of depression.  Currently, research is at a crossroads of learning more of these mechanisms to create better treatments for depression.

Treatments Used in Research:

SSRI’s ( Selective Serotonin Reuptake Inhibitors)

Block the reuptake of serotonin (5-HT), an excitatory neurotransmitter in the brain that plays an important role in mood control, causing more 5-HT to stay at the synaptic cleft and allow for more signaling to other neurons

Common SSRI Drugs: Prozac, Zoloft, Praxil, Celexa, Lexapro, Luvox



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Tricyclic Antidepressants

Block both the 5-HT and norepinephrine, also an excitatory neurotransmitter in the brain involved in arousal, reuptake at their respective receptors allowing more signaling to other neurons using both of these chemicals

Common Tricyclic Drugs: Anafranil, Adapin, Aventyl, Elavil, Norpramin, Pamelor, Pertofrane, Sinequan, Surmontil,Tofranil, Vivactil

Research

Malberg et al. (2000) first suggested the possibility that neurogenesis supports the therapeutic effect of antidepressants in a rat model for depression.  The antidepressants studied were monoamine oxidase inhibitor (tranylcypromine), a serotonin-selective reuptake inhibitor (fluoxetine),and a norepinephrine-selective reuptake inhibitor (reboxetine), as well as elecroconvulsive shock, also an effective treatment for depression.  Malberg et al. (2000) found that all of the treatments increased the proliferation of neurons in the subgranular zone (SGZ) and proposed that this increase is a mechanism to fight depression.

Santarelli et al. (2003) found that treatments of the antidepressants fluoxetine and imipramine, a tricyclic antidepressant, increase neurogenesis in a mouse model of depression.  Also, by blocking neurogenesis, both of these drugs were found to lose their behavioral effects.  This finding supports the theory that antidepressants work through an increase of neurogenesis.  However, in an eating latency test, in which animals were determined to be depressed when their eating decreased, so called depressed mice showed the same rate of neurogenesis as the non-depressed mice.  This showed that the change in behavior was not due to a decrease in neurogenesis.

Henn and Vollymar (2004) report, along with Santerelli et al. (2003) and Malberg and Duman (2003), that a reduction of neurogenesis is the cause of depression-like behaviors.  Later, Sahay and Henn (2007) reported that adult mice lacking neurogenesis did not show a greater susceptibility to depression like behaviors.  To this point it is believed that neurogenesis is necessary for the treatment of depression using SSRI’s and tricyclic antidepressants, however depression is not caused by a decrease in neurogenesis.

Castren and Rantamaki (2009) suggest that brain-derived neurotrophic factor (BDNF) plays a crucial role in neurological recovery from depression.  They propose a theory that abnormal neuronal networks are formed during adverse conditions in important stages of development.  This causes an increase in the expression of BDNF and allows the brain to recover from adverse conditions in the future.  Depressed patients show a decrease in blood levels of BDNF, however, treatment can normalize the levels.   There is evidence that mechanisms of antidepressant drugs involve BDNF signaling.  Therefore, there is a possibility that BDNF is used as a sort of guide to fix abnormal neurological connections and fight the symptoms of depression.

As one can tell, the research up to this point on the role of neurogenesis in depression and its treatments are ambigous.  However, there has been research reporting a relationship between the two.  This leads researchers to believe that through further understanding of the mechanisms underlying depression and antidepressant drugs, more conclusive findings will be reached. To learn more of the possible implications this research has helped inspire see potential applications.

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Aknowledgments

Depressed Person: http://ocw.jhsph.edu/courses/PsychiatricEpidemiology/

Symptoms of Depression : http://www.pristiq.com/depression_symptoms.aspxc

Common Antidepressant Drugs: http://www.webmd.com/depression/recognizing-depression-symptoms/antidepressants

SSRI Diagram : www.lidtke.com/townsend/index.htm

Tricyclic Antidepressants Diagram and information: http://www.cnsforum.com/imagebank/item/Drug_TCA_efficacy/default.aspx

Page Authors: Ian Dell

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