A research team has found an association between genetic irregularities and white matter, a feature of brain structure known to be disrupted in schizophrenia. These findings help shed light on the illness.

Reporting their findings May 27th in European Journal of Human Genetics, the team included five NARSAD-funded researchers: 2002 and 2006 Young Investigator grantee Tonya J. H. White, M.D., Ph.D.; 2010 Young Investigator grantee Stefan Ehrlich, M.D.; 2004 Young Investigator Vince D. Calhoun, Ph.D.; 1999 and 2004 Young Investigator and 2014 Independent Investigator grantee Vincent A. Magnotta, Ph.D.; and 2002 Young Investigator and 2007 and 2010 Independent Investigator grantee Beng-Choon Ho, M.D.

White matter consists of cells that create a protective layer around the wire-like extensions of neurons, which reach out to transmit signals to other cells. The protective sheathing, which also helps the signals travel faster, consists of a material called myelin, and the cells that build it are called oligodendrocytes. Oligodendrocytes differ from neurons in that they support signaling in the brain but are not themselves involved in nerve signal transmission.

White matter integrity is known to be decreased among people with schizophrenia. For the first time, a research team has also found that decreased white matter integrity among patients is linked with mutations in genes that code for oligodendrocytes, as well as a mutation in a neuronal gene that regulates myelin sheathing. These associations point to a relationship between white matter abnormalities and genetic irregularities affecting myelin sheathing. This relationship is relevant to the development of schizophrenia.

“Perhaps what is unique about the approach our team took is that we looked at multiple genes involved in similar functions and it was not one gene alone that resulted in the differences, but the combined small effects from multiple genes,” Dr. White said.

The link between schizophrenia and myelination-related genetic mutations was found whether or not the patients had abnormal white matter. This suggests that these mutations relate to schizophrenia through added mechanisms beyond white matter integrity.

The team says their findings help identify potential indicators of schizophrenia risk: white matter integrity is a potential structural indicator, and the identified mutations to oligodendrocytes and neuronal genes are possible genetic indicators. Future research will aim to determine whether schizophrenia can one day be treated with myelination-related proteins that shield against the loss of white matter integrity.

Read the abstract.