Depression & the Serotonin System
Depression is one of the leading causes for disability WORLDWIDE.
There are currently 121 million people worldwide who are affected by depression.
Only 25% — ¼ — of those individuals have proper access to effective treatment for the disease.
THEN, of that 25% of depressed patients, only about 60 to 80 % report to have been treated effectively.
This means that roughly 25 to 50 million people worldwide experience no relief from their systems, and receive no adequate treatment.
Despite all of these statistics that indicate that depression is nearly unbeatable in many cases, it can in fact be diagnosed and treated in primary care.
So – how is depression treated? The simple answer is that depression individuals are more often than not prescribed anti-depressant drugs. These anti-depressants, sometimes called AD’s, work by elevating levels of brain norepinephrin, which is more commonly known as serotonin.
HOWEVER, typically, the effects of AD therapy lag about 3 to 4 weeks behind this elevation in brain serotonin levels – and THIS finding suggests that long-term changes neural plasticity or neurochemistry are mediating antidepressant effects. The enzyme that is responsible for the synthesis of serotonin in the brain is called tryptophan hydroxylase 2 (TPH2), and mutations in the TPH2 gene have been strongly associated with major depression and responses to antidepressants.
Thus, this brings me to the focus of the lab that I have been working with since joining the Research Scholars Program.
We are currently investigating the effects of brain serotonin deficiency in response to AD’s.
In order to do this, my mentor and I have been comparing the cellular responses of WT mice and mice with a ‘loss of function’ mutation in their TPH2 gene to chronic treatment with antidepressants.
So far, we know that CHRONIC and NOT ACUTE treatment with fluoxetine (the active ingredient in AD’s like Prozac) for 3 weeks leads to increased neurogenesis in the dentate gyrus of the non-mutant mice, while those mice with mutant forms of TPH2 no show increased neurogenesis.
NOW, we are in the process of determining whether serotonin supplementation in mutant TPH2 mice restores the therapeutic effectiveness of fluoxetine by restoring the ability to increase neurogenesis in the dentate gyrus.
And just to clarify, serotonin supplentation simply means that we administer the neural serotonin precursor – 5-HTP— to the mice with the TPH2 loss of function mutation.
As it stands, the goal of this study is to eventually make it possible to screen depression patients for TPH2 mutations or for brain 5-HT (serotonin) deficiency, thereby allowing medical professionals to specifically treat those individuals with a combined SSRI (antidepressant) AND serotonin supplementation strategy.