Whole genome scan finds depression hotspots

A whole genome analysis has identified 19 specific regions very likely to contain genetic variations that raise the risk of a severe form of depression. The new study indicates that one of the "susceptibility loci", which contains a gene called CREB1, plays a particularly big role in the illness.

"We can't do better than this," says George Zubenko of the University of Pittsburgh Medical School, who led the work. "This is the strongest statistical evidence for any susceptibility locus for any psychiatric disorder reported to date." The likelihood that the observed genetic linkage of recurrent depression to CREB1 resulted from chance is less than one in a billion, the researchers say.

Previous studies had implicated CREB1 in depression but the link in the new study was unusually strong, especially in women. The gene produces a protein that has a number of functions in the nervous system. Investigation of this and other loci will help identify new drug targets.

The work is "tremendously exciting", says John Kelsoe of the University of California, San Diego. "This is one of the strongest findings for any psychiatric disorder I've seen."

Since 1986, Zubenko and his colleagues have followed a group of 81 families with a high incidence of recurrent, early-onset, major depressive disorder (RE-MDD). This form of the illness is highly heritable, but some members of these families instead suffer from milder forms of depression.

The researchers used blood samples to assemble complete genetic profiles of 520 people from these families. They then compared the genomes of individuals who suffered the severe, recurrent depression with those who had the milder forms. This analysis produced the 19 significant genetic "peaks".

In general, depression is twice as common in women as in men and the new study backed this. The team found the link between severe depression and CREB1 was even stronger in women than in men. Zubenko told New Scientist that CREB1 protein interactions with hormones may cause the sex differences in depressive illness.

Journal reference: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics.

Peter Farley

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