Treating Depression: Is Neurogenesis the Answer?
Most people are aware that their skin cells are continually dying off and being replaced. Perhaps there is less awareness of the fact that nerve cells in the brain do much the same thing. A bit like our skin it’s a cycle in which dead cells are simply replaced. The formation of new nerve cells is known as neurogenesis. In people who are depressed there is evidence that degeneration of nerve cells in the brain is faster than replacement. Indeed there is physical evidence that an area of the brain called the hypothalamus can be shrunk by as much as 10 percent in people who suffer from depression.
So what’s the relationship between this and what we know about antidepressants? In a previous Sharepost – Time to Close the Curtain on the Serotonin Show? - I pointed to the fact that antidepressant medication has a fairly patchy track record when it comes to treating depression. Conservatively, around 50 percent of those treated with antidepressants fail to respond. Actually the figure is likely to be higher than this, possibly as much as 70 percent. Perhaps because of the popularity of the newer antidepressants the idea took hold that depression was due to some form of chemical imbalance in the brain. Top up the serotonin levels and improvements would be seen (or not more likely).
Accepting the fact that SSRI antidepressants do appear to have a positive effect in some people, the question to be asked is, why should it take at least 4-6 weeks before an effect is seen? If we have a headache and take an aspirin the effects are fairly rapid, yet we don’t accept that headaches are due to a lack of aspirin in the body. Even if we accept that serotonin influences mood (which it does) it still doesn’t explain why it takes so long. This is exactly the issue that various researchers have been tackling. If there is a delay between taking antidepressants and their effects it suggests some other process or processes are at work – but what are they?
The neurogenesis theory of depression points to serotonin as a mechanism that stimulates new neural growth. Yet its effects are quite slow, sometimes minimal and appear ineffective in many people with depression. It’s early days yet but researchers may be tapping on the door behind which are answers. Last year, for example, the journal Nature Medicine published interesting findings involving ceramide. Ceramide can be thought of as fatty molecules. In the brain the action of ceramide appears to block brain cell growth. In mice studies it was found that the action of drugs such as Prozac was actually to decrease levels of ceramide in the brain. So rather than additional serotonin giving relief to depressive symptoms it was actually by blocking the effects of ceramide which provided some scope for neurogenesis.
Let’s not get too excited. Although the neurogenesis theory explains the time frame necessary to see an effect the science is still in its formative stages. Results are patchy and this is further compounded by the fact that knowledge into the neurogenesis mechanism is still developing and many questions remain to be answered.
Billings, K (2014) The Future of Depression Treatment: The Neurogenesis Theory. Biological Sciences, Feb.
E. Gulbins et al, Nat. Med. 19, 934-938 (2013).