One of the conundrums about modern psychotherapy is that while we know SSRIs work to alleviate symptoms of unipolar depression, nobody is sure exactly why. That is to say, we know that the drugs inhibit the reuptake of serotonin, but what does that neurotransmitter have to do with depression?
The neurogenesis hypothesis is one proposed way to explain how depression functions in the brain. Most of the neurogenesis in humans takes place in the dentate gyrus of the hippocampus (although there is some olfactory neurogenesis as well). There are two parts to the hypothesis:
1) That there is a causal relationship between neurogenesis and depression. This largely relies on correlative and indirect evidence, such as the link between stress and neurogenesis, and the link between stress and depression. However, in order to show a causal relationship, then depression would have to lead to a decreases in neurogenesis, which is not the case in rodents (see Vollmayr et al., 2003). So the first part of the hypothesis has been (mostly) placed aside for the time being.
2) That anti-depressants may work via the stimulus of neurogenesis. This remains a viable idea (Santarelli et al., 2003), although the evidence supplied is primarily in non-humans.
All of this leads to yesterday, when the MIT Tech Review reported that a drug specifically stimulating neurogenesis was going to clinical trials. It will be interesting to see how effective the drug is. And if part 2 of the neurogenesis hypothesis holds true, then it is indeed possible that patients who don’t respond to SSRIs may respond to a drug that stimulates hippocampal neurogenesis directly.
Again, we shall see.
Link to article in the MIT Technology Review.
L. Santarelli, M. Saxe, C. Gross, A. Surget, F. Battaglia and S. Dulawa et al., Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants, Science 301 (2003), pp. 805–809.
B. Vollmayr, C. Simonis, S. Weber, P. Gass and F. Henn, Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness, Biological Psychiatry 54 (2003), pp. 1035–1040.