Study Links Genes Involved in Early Brain Development to Late-Onset Psychiatric Disorders

Researchers in the United Kingdom have, for the first time, linked genetic disruption of specific cell processes crucial to early brain development with the risk of developing psychiatric disorders that manifest later in life, such as bipolar disorder and schizophrenia.

Using human pluripotent stem cells, the team at Cardiff University identified sets of genes switched on during the early development of human brain cells. The genes appeared to play distinct functional roles, in the process, also known as neurogenesis. In vitro experiments showed that when activation of these gene sets is disrupted, the shape, movement and electrical activity of developing brain cells is altered. Disorders linked to disruption of these genes include early onset conditions such as developmental delay, ADHD, and autism, as well as late-onset conditions like bipolar disorder and major depression. Because they are switched on well before birth, genes involved in early brain development were previously not thought to play a role in disorders that begin to show symptoms in adolescence or adulthood.

“Genetic factors play a significant role in determining a person’s risk of developing psychiatric disorders,” says Andrew Pocklington, a lead author on the study and Senior Lecturer at Cardiff University’s Division of Psychological Medicine and Clinical Neurosciences. “Uncovering biological processes impacted by these genetic risk factors is a major step towards understanding the causes of disease.”

Previous studies have shown that genes active in mature brain cells are enriched for common genetic variants contributing to schizophrenia, Pocklington adds. “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 pre-natal brain may remain active in later life, with genetic variation in these pathways contributing to disease by disrupting both development and mature brain function.”

Dr. Eunju Jenny Shin, a lecturer at Neuroscience and Mental Health Research Institute at Cardiff University while jointly leading the study, said the work “may ultimately help guide the development of novel therapies or help explain why some individuals respond to some treatments but not others.”

The findings were published recently in the journal Nature Communications.