Canadian scientists have identified a gene that makes some people susceptible to major depressive disorders. Speaking at the Forum of European Neuroscience today (9 July), Professor Nicholas Barden explained, "This is a major breakthrough in the realm of psychiatry and will have groundbreaking implications for diagnosis and the development of new anti-depressant treatment." It has been known for many years that genetic factors are at the base of depression and bipolar disorder, but the complex molecular networks involved remain unknown. "The actual gene, known as P2RX7, is found in humans and animals and is responsible for depression. It has taken many years to find," said neuroscientist, Professor Barden from CHUL Research Centre in Quebec.
Finding it is highly significant in uncovering the molecular pathways involved in depression. The results were published in May 2006 American Journal of Medical Genetics* During their lifetime, about 5-12% of men and 10-25% of women will experience at least one episode of major depression. People with bipolar disorder - also known as manic depression - experience extreme mood swings. The total social cost of depressive disorders is estimated to be billions of dollars per year. By 2020, depression is expected to rank first in disease burden in economically developed countries.
Depression has until now often been associated with the serotonin system in the brain, a system that can influence mood and emotion. "What is particularly exciting is that P2RX7 has nothing to do with serotonin," said Professor Barden. Drugs that boost the flow of serotonin can be effective anti-depressants, but take weeks to take effect.
The fact that P2RX7 that has nothing to do with serotonin could partly explain why. Animal studies have shown that this gene is expressed in brain areas known to be involved in depression, and depressive-like behaviour in mice could be reversed by treatment with drugs that stimulate P2RX7. P2RX7 also plays an important role in the brain's response to inflammation, which is known to be part of many neuropsychiatric disorders. Additionally, stress hormones decrease the activity of this gene, suggesting a mechanism for the onset of depression following severe stress. "A person may have the mutated gene, but its 'default setting' means that they may not develop depression. We don't yet know how P2RX7 works and we still believe that a multitude of genes feed into the same pathway that may induce depression," said Professor Barden.
The identification of the gene means that anti-depressants in the future could target the gene directly. With anti-depressants currently targeting the serotonin system, P2RX7 is bypassed to an extent. In animal studies, activators of P2RX7 have an immediate anti-depressant action, giving hope that new anti-depressant medication, with a new mechanism of action, can be developed.
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