Study confirms schizophrenia gene link

A new study provides more evidence that a gene which affects levels of a key brain chemical is involved in schizophrenia. A team based at Stanford University in California, US, found that children with a single, 'low-activity' copy of a gene called COMT (catechol-O-methyl transferase) are at higher risk of developing psychotic symptoms than those with a single 'high-activity' copy of the gene. The researchers, who published their findings online in the journal Nature Neuroscience, say they hope that the research will lead to new treatments for schizophrenia, and new ways of detecting people at high risk of the condition.

Schizophrenia is one of several brain disorders thought to involve an imbalance in levels of dopamine, a key brain communication chemical. Too much or too little dopamine can dramatically affect a person's thought processes, movement, or behaviour. The COMT gene makes a protein that breaks down dopamine in the brain, and comes in two different versions - the more active 'val' form, and a less active 'met' variety.

In the latest study, the scientists looked at children born with a small part of one of their two chromosome 22s missing, or deleted. This deletion encompasses the COMT gene, as well as several other genes. It causes a condition known as velocardiofacial syndrome, which is characterised by special facial features, heart defects and cleft problems. The condition also raises the risk of developing a psychotic disorder such as schizophrenia to 30 per cent, compared to the average population risk of one per cent.

The team wanted to investigate if, in children born with a copy of COMT missing, alternative versions of the remaining gene affected the risk of psychotic symptoms. So the scientists studied 24 children born with a chromosome 22 deletion, and compared them with 23 children who had an unknown developmental disorder. At the beginning of the study, none of the participants showed any signs of psychosis. However, five years later, when they were teenagers, seven (29 per cent) of those with the deletion had developed a psychotic disorder, compared to just one in the control group. Furthermore, the children with a deletion and a low activity 'met' version of COMT on their other chromosome 22 had more severe symptoms, compared to those born with a deletion and a high activity 'val' version.

The scientists think that having just one, low activity version of COMT can lead to damagingly high levels of dopamine in the developing brain of a child with velocardiofacial syndrome. They liken the process to dialing-in a radio station - dopamine levels need to be precisely tuned, not too much or too little, to maximise the signal and minimise the noise. Team leader Allan Reiss said: 'Although this deletion probably causes less than five per cent of schizophrenia cases, it's the only well-defined genetic risk factor we have right now', said, adding 'in the future, researchers will likely discover multiple causes of this disorder, with complex interactions between genetic and environmental risk factors'.