Study uses new approach to study genetic origins of mental illness

A study in Biological Psychiatry establishes an in vitro model for the development of human neurons to study the genetic risk of psychiatric illness

A study in Biological Psychiatry has developed a new analytical method to study the complex genetic origins of mental illnesses using brain cells developed in a box from human embryonic stem cells. Researchers at the University of California at Los Angeles examined the process of identifying new neurons for certain roles and found that changes in gene expression during neural development were significantly associated with the genetic risk of schizophrenia. .

"Our approach has allowed us to model how many areas of the genome that increase the risk of psychiatric disorders work together to affect the molecular and cellular function that is important for neurodevelopment." It's exciting as it provides a new framework. for the study of the genetic risk of psychiatric diseases and shows that we can capture elements of the heritability of schizophrenia in a laboratory model system, "said the first author and doctoral candidate, Anil Ori, MSc .

The study of the biology of the disease and the heritability of schizophrenia in model systems is a challenge because of the genetic complexity of psychiatric illnesses. "[Large-scale population studies] have shown that psychiatric disorders are inherited traits in which hundreds, if not thousands of genes in the human genome contribute to the risk of disease, "said lead author Roel Ophoff, PhD. This accumulation of many minor gene effects is called risk polygenic.

"The translation of polygenic risk into neurobiology is one of the major scientific challenges of psychiatry at this time.This article highlights a new approach to starting this work," said John Krystal, MD, director of Biological Psychiatry.

The new approach has incorporated the polygenic nature of schizophrenia by tracking changes in gene expression during the development of human neural stem cells. By integrating gene expression patterns into genome-wide schizophrenia risk data, the first author, Anil Ori and colleagues, found that genes differentially expressed during development were associated at a polygenic risk of schizophrenia. They reproduced this result in the study using a different sample.

According to the authors, the results will help researchers to identify the critical pathological processes contributing to the risk of disease. In the study, genes primarily responsible for association with risk of disease were involved in synaptic function, the means by which cells communicate and transmit signals across the brain.

"The establishment of this platform for further studies has considerable potential benefits," Ori said. Now that the study has established in vitro neuronal development as a model for psychiatric illnesses, researchers can modify the model to examine how different environments might affect disease risk and use it to understand the disease. biology of mental illnesses.

"While large-scale genetic studies on psychiatric disorders will continue to develop, our study provides a valuable genomic tool to help investigate and understand how distributed risk in the genome contributes to the etiology of psychiatric disorders" said Dr. Ophoff.