Mixed signals

Two of the aberrations discovered in the new study were in genes used in a major signaling system in the brain,giving clues to processes that might go awry and suggestions of how to treat the diseases.

What we identified here is probably just the tip of an iceberg, said Dr Jordan Smoller,lead author of the paper and a professor of psychiatry at Harvard Medical School and Massachusetts General Hospital.

The new study does not mean that the genetics of psychiatric disorders are simple. Researchers say there seem to be hundreds of genes involved and the gene variations discovered in the new study confer only a small risk of psychiatric disease.

The work began in 2007 when a large group of researchers began investigating genetic data generated by studies in 19 countries and including 33,332 people with psychiatric illnesses and 27,888 people free of the illnesses for comparison. The researchers studied scans of peoples DNA,looking for variations. The question: Did people with psychiatric illnesses tend to have a distinctive DNA pattern in any of those locations?

About six years ago,around the time the new study began,researchers had examined the genes of a few rare families in which psychiatric disorders seemed especially prevalent. They found a few unusual disruptions of chromosomes that were linked to psychiatric illnesses. But what surprised them was that while one person with the aberration might get one disorder,a relative with the same mutation got a different one.

Jonathan Sebat,chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at the University of California,San Diego,and one of the discoverers of this effect,said that work on these rare genetic aberrations had opened his eyes. Two different diagnoses can have the same genetic risk factor, he said.

No one had systematically looked at the common variations, in DNA,he said. We didnt know if this was particularly true for rare mutations or if it would be true for all genetic risk. The new study,he said,shows all genetic risk is of this nature.

The new study found four DNA regions that conferred a small risk of psychiatric disorders. For two of them,it is not clear what genes are involved or what they do,Dr. Smoller said. The other two,though,involve genes that are part of calcium channels,which are used when neurons send signals in the brain.

The calcium channel findings suggest that perhaps and this is a big if treatments to affect calcium channel functioning might have effects across a range of disorders, Dr. Smoller said.

There are drugs on the market that block calcium channels they are used to treat high blood pressure and researchers had already postulated that they might be useful for bipolar disorder even before the current findings.

One investigator,Dr. Roy Perlis of Massachusetts General Hospital,just completed a small study of a calcium channel blocker in 10 people with bipolar disorder and is about to expand it to a large randomized clinical trial. He also wants to study the drug in people with schizophrenia,in light of the new findings. He cautions,though,that people should not rush out to take a calcium channel blocker on their own.

We need to be sure it is safe and we need to be sure it works, Dr. Perlis said.