Genetic Regulation of Brain Development Implicated in Mental Illness

By Rick Naurert PhD
March 19th, 2023
Medically reviewed by Paul Sietes, MD.

A major study of the genes associated with psychiatric illnesses has discovered that most of the genes are in place before birth in the developing human brain.

Yale University researchers also discovered that hundreds of genetic differences were found between males and females as their brains take shape in the womb.

The study is  found in the journal Nature.

Neuroscientists estimate  the human brain has a hundred billion brain cells requiring an incalculable number of connections.

In the study, Yale researchers tracked 86 percent of 17,000 human genes that are believed to be recruited in the effort to create the brain.

Investigators studied not only what genes are involved in development, but where and when they are expressed, or activated.

“We knew many of the genes involved in the development of the brain, but now we know where and when they are functioning in the human brain,” said Nenad Sestan, M.D., Ph.D., senior author of the study.

“The complexity of the system shows why the human brain may be so susceptible to psychiatric disorders.”

The study identified genes represented in the human brain, and when and where in the brain they were expressed. Scientists used more than 1,300 tissue samples taken from 57 subjects, aged from 40 days after conception to 82 years.

The analysis of over 1.9 billion data points by the Yale scientists created an unprecedented map of genetic activity in the brain at different stages of development.

Researchers were impressed to find much of the human brain is shaped prior to birth.

For instance, the team analyzed genes and variants previously linked with autism and schizophrenia, the symptoms of which are evident in the first few years of life or during early adulthood, respectively. The new analysis shows molecular evidence of expression of these suspect genes prior to birth.

“We found a distinct pattern of gene expression and variations prenatally in areas of the brain involving higher cognitive function,” Sestan said. “It is clear that these disease-associated genes are developmentally regulated.”

When comparing the brains of men and women, researchers noticed that in addition to the Y chromosome gene found in only in men, each gender presents distinct differences in many of genes that are shared by both sexes.

This difference was noted both for when the gene was expressed and the level of the gene’s activity. Most of the differences were noted prenatally.

Source: Yale University

Dr. Rick Naurert has over 25 years experience in clinical, administrative and academic healthcare. He is currently an associate professor for Rocky Mountain University of Health Professionals doctoral program in health promotion and wellness. Dr. Naurert began his career as a clinical physical therapist and served as a regional manager for a publicly traded multidisciplinary rehabilitation agency for 12 years. He has masters degrees in health-fitness management and healthcare administration and a doctoral degree from The University of Texas at Austin focused on health care informatics, health administration, health education and health policy. His research efforts included the area of telehealth with a specialty in disease management.