Genetics play a 'significant' role in risk of psychiatric disorders

Changes in brain cells during early life are associated with the early onset of developmental delays, autism, ADHD, but also conditions that typically come later in life, such as bipolar disorder and major depression.

Dave Yasvinski 3 minute read January 18, 2022
Colors of emotions

They discovered that the genetic risk factors associated with schizophrenia and other psychiatric disorders were highly concentrated in gene sets. GETTY

Scientists studying the birth of brain cells have discovered a link between the breakdown of cell development and the risk of psychiatric disorders, including autism, major depression and schizophrenia.

The study, published in the journal Nature Communications, sheds light on the process by which genetic risk factors can disrupt certain cell processes vital to brain development.

“Genetic factors play a significant role in determining a person’s risk of developing psychiatric disorders,” said Andrew Pocklington, co-leader of the study from the division of psychological medicine and clinical neurosciences at Cardiff University. “Uncovering biological processes impacted by these genetic risk factors is a major step towards understanding the causes of disease.”

To get a better sense of why certain conditions arise later in life, the team went back to the beginning.

“To truly understand the root causes of psychiatric disorders, we focused on studying the development of brain cells,” said Eunju Jenny Shin, the other co-leader of the research. “The knowledge gained through this approach may ultimately help guide the development of novel therapies or help explain why some individuals respond to some treatments but not others.”

By observing this early development using human pluripotent stem cells, the team was able to identify several sets of genes that are switched on during the early stages of life — either in vitro or in the fetal brain — with each set playing a distinct functional role. They discovered that the genetic risk factors associated with schizophrenia and other psychiatric disorders were highly concentrated in these gene sets.

“In vitro experiments showed that when activation of these sets is disrupted, the shape, movement and electrical activity of developing brain cells is altered, linking changes in these properties to disease,” Shin said.

These changes are associated with the early onset of certain psychiatric disorders — such as developmental delay, autism and ADHD — but also, unexpectedly, other conditions that typically present later, such as bipolar disorder and major depression. Because some of these genes are switched on long before birth, the finding raises the possibility that they can be therapeutically targeted later in life.

“Previous studies have shown that genes active in mature brain cells are enriched for common genetic variants contributing to schizophrenia,” Pocklington said. “Much of this enrichment was captured by the early developmental gene sets, which seem to contain a greater burden of common genetic risk factors.

“This suggests that some biological pathways first switched on in the early prenatal brain may remain active in later life, with genetic variation in these pathways contributing to disease by disrupting both development and mature brain function.”

More research will be required to detail the range of developmental processes that are disrupted by different disorders and the long-term effects these disruptions have on the brain, Shin said.

“Although much remains to be uncovered, our findings provide valuable insight into the developmental origins of psychiatric disorders such as schizophrenia.”

Dave Yasvinski is a writer with  Healthing.ca. He can be reached here.

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