THE first clear evidence of how antidepressant drugs help to boost brain cell formation could lead to better treatments for depression.
The hippocampus is one of just two brain regions known to grow new neurons throughout life – a process called neurogenesis. This process is disrupted in people with depression, although it is not known whether this is a cause or symptom of the condition. It is clear, however, that one of the ways that antidepressants work is by boosting neurogenesis in the hippocampus. Christoph Anacker and his colleagues at King’s College London have now worked out how they do so.
Previous research has shown a link between some antidepressants and stress hormones called glucocorticoids. So Anacker’s team decided to test whether the antidepressant sertraline acts on the glucocorticoid receptors of brain cells. They grew human hippocampal progenitor cells in a dish and added sertraline. Ten days later, the cultures showed a 25 per cent greater than expected increase in the number of new neurons.
When the researchers added a drug to block the glucocorticoid receptors before adding the antidepressant, the number of new neurons produced after 10 days was similar to that expected from natural growth. This suggests that the antidepressant does indeed exert its effect through this receptor (Molecular Psychiatry, DOI: 10.1038/mp.2011.26).
“Both glucocorticoid hormones and antidepressants activate this receptor, but they do so in very different ways,” says Anacker. He thinks the result will enable researchers to develop more effective antidepressant drugs with this specific target.
Allan Young of Imperial College London agrees. “The results suggest that we should be focusing our efforts on developing medicines for depression which act directly on the stress hormone system.”