Many scientists have drawn another blank in their search for a universally applicable genetic explanation for schizophrenia, binding the case for new approaches to researching the illness. A paper by Douglas F. Levison and colleagues report that despite earlier findings to the contrary, there is no close link between schizophrenia and genes on the long arm of chromosome 1.
The researchers scoured the chromosome in more than 1,900 patients before reaching this conclusion."Schizophrenia is a complex psychiatric disorder," said co-author Dr Ann Pulver of Hopkins University. "It can't be explained by either a single altered gene or a single environmental cause. There are clearly genetic components, but they are likely to be varied and to interact in many ways with non-genetic factors."
She added that it was still possible that genes on chromosome 1 may contribute to schizophrenia, but they would influence only a small proportion of patients. Dr Philip Ward of the US National Institute of Schizophrenia and Allied Disorders said the findings underscored the need for a new method to "get a handle" on the condition.
"A previous study in Science showed that there was a highly significant link to this gene," he said. "However this multicentre study shows that this does not hold across a range of populations." Dr Ward said that since the discovery of the first genetic linkage with schizophrenia, which made the cover of Nature in 1995, genes on chromosomes 6, 8, 13, 22 had been linked to schizophrenia.
"The trouble has been to get the link to replicate across different populations," he said. According to Dr Ward, such findings raise questions about the approach that needs to be taken in research. Schizophrenia is known to involve genetic factors, since people who have relatives with the condition are more likely to have it, with 40 to 60 per cent concordance between identical twins.
"This tells us there's something genetic but that it's not that simple otherwise there'd be 100 per cent concordance in identical twins," said Dr Ward. "We need to stop hoping to luck upon a single genetic magic bullet and start thinking about what makes people susceptible." He said it was not schizophrenia itself that was inherited, but rather risk factors that predisposed people to the condition.
There were various clues that suggested these risk factors include problems with attention and reading, problems with fine motor co-ordination, obstetric complications, and older fathers, he said. The risk factor approach is already common in research on cancer, heart disease and diabetes, but schizophrenia researchers do not yet have the large database of evidence gathered by researchers in other fields.
One limitation had been that diagnosing schizophrenia is based on self-assessed symptoms, said Dr Ward. There's no lab test for hallucinations, you just rely on the patient saying they are having them." More holistic studies, looking at the brain structure, function, and genetics of closely-related people with schizophrenia would help the field go forward, he said. We need to go beyond diagnosis to find biophysical markers." This would enable more targeted, individualised, and evidence-based treatments.