An international team of researchers have for the first time shown that natural variations in a specific gene influence brain structure.
This study may help improve the scientific understanding of autism and other neurological disorders.
Co-led by Scripps Research Institute scientists, the research grew out of a larger project called the Thematic Organized Psychosis (TOP) study, which was led by Ole Andreassen at Ullelval University Hospital and Institute of Psychiatry at the University of Oslo in Norway.
TOP called for using extensive magnetic resonance imaging (MRI) scanning of hundreds of patients, including many with severe mental disorders, in collaboration with Anders Dale of the University of California, San Diego (UCSD), School of Medicine.
In the current study, the researchers focused on a gene called MECP2 because it plays major roles in controlling brain development.
Past studies with mice have shown that MECP2 regulates the activity of a wide range of other genes important in brain development. Substantial mutations in the gene also cause the rare disease Retts syndrome, in which brain growth slows, leading to a range of debilitating neurological problems and mental retardation.
Previous studies have also linked MECP2 to autism.
Given its obvious import, Schork says: "This was a logical gene to target."
During the study, the researchers explored whether common variations likely to have small effects individually in the MECP2 and surrounding region in the DNA of patients could be tied directly to the way a patient's brain develops.
They found that indeed some of these variations, known as single-nucleotide polymorphisms (SNPs), did correlate well with various measures of a patient's brain, though there was no identifiable tie between the variations and the mental disorders.
The closest connection they found was between two specific SNPs and lower surface area folds of the outer layer, or cortex, of the brain-the "grey matter," which plays critical roles in thinking, language, memory, and other functions.
"So, those sorts of common variations actually do have some functional consequences that are dictating variations in brain size," says Schork.
Interestingly, the pattern was only seen in males.
Schork and his colleagues say that because MECP2 has been linked to autism, there is a very real possibility that studying SNPs in autistic patients might reveal one or more that link to brain development problems. This could even illuminate possible paths for autism treatments, they say.
The researchers are also looking at possible connections between variations in other key genes and various brain regions.
Besides overall brain size, researchers believe that some neurological conditions might be tied to increases in the size of certain brain components, perhaps due to unidentified genetic mutations. This could prevent other components from growing to their full size due to the limited space inside a skull, preventing proper functioning.
"Who knows? This opens things up considerably. Now we can cast a much wider net and maybe rope in genes nobody had a clue about and discover something that otherwise wouldn't have been known," says Schork.
The study has been reported in an advance, online Early Edition of the Proceedings of the National Academy of Sciences (PNAS).