Emerging evidence suggests many people with schizophrenia have small genetic abnormalities that affected their brain in childhood and adolescence.
In a series of new studies on adult onset schizophrenia, NIH scientists discovered individuals possessed high rates of rare genetic deletions and duplications that apparently disrupted their brain during youth.
These tiny anomalies were found in 15 percent of adult onset schizophrenia patients and 20 percent of child and adolescent onset patients, compared with only 5 percent of healthy participants.
Collectively, the mutations carried by patients were significantly more likely than those in healthy participants to disrupt genes involved in brain development — potentially implicating hundreds of genes in the illness, which affects about 1 percent of adults.
“This is an important new finding in the genetics of schizophrenia,” said NIMH Director Thomas R. Insel, M.D.
“Identifying genes prone to harboring these mutations in brain development pathways holds promise for treatment and prevention of schizophrenia, as well as a wide range of other neurodevelopmental brain disorders.”
Two independent teams of researchers report on their combined findings in an article published online in Science Express, March 27, 2008.
The prevailing genetic model of schizophrenia implicates common variants of certain suspect candidate genes, each exerting modest effects, in interaction with each other and environmental factors. This hypothesis holds that risk stems from common variations in the sequence of the genetic code that result in altered protein products.
About a year ago, researchers reported evidence strengthening the case for a different kind of genetic risk. Many people with autism were found to have different, spontaneous and individually rare structural variations — variations in the number of copies of genes. These copy number variations were scattered throughout the genome, suggesting that many different genes could be involved in autism spectrum disorders.
The new findings in schizophrenia echo those in autism, but also broaden their implications. The results suggest a new approach for discovering genes for schizophrenia and other mental disorders, say the researchers. Any mutation in the hundreds of genes involved in brain development could lead to a different set of neurodevelopmental consequences – schizophrenia, autism, mental retardation, or no illness at all. Each person with one of the illnesses could have a different genetic cause for the disorder.
The functional consequences of these structural genetic variations may differ, depending on interactions with other genes or environmental events, say the researchers, making any gene harboring a deleterious structural mutation a “candidate gene.” Any gene harboring one mutation likely contains others. Although each might be individually rare, together such disease-causing variations in one gene could explain a substantial number of illness cases, they suggest.
Among key study findings: