Stress Gene Is 'Stuck On' in the Brains of People With Schizophrenia, Study Finds

Researchers at the University of Sydney, working with the Max Planck Institute of Psychiatry in Germany, have found that a gene involved in regulating the body's stress response switches on more easily in the brains of people with schizophrenia. The study, published in the American Journal of Psychiatry, examined the FKBP5 gene and its FKBP51 protein, which help control how strongly the body responds to stress hormones such as cortisol.

Using donated brain tissue, the researchers found that in people with schizophrenia, the chemical tags that normally keep the FKBP5 gene in check had been stripped away through a process called DNA methylation, and this was linked to higher activity of the gene. Dr. Natalie Matosin of the University of Sydney's School of Medical Sciences said this is "like having the volume on their speaker stuck on high," and that responding to stress this strongly can affect the brain over time, making it more vulnerable to serious psychiatric conditions.

The researchers also found that these changes in the stress-response system become more pronounced with age, meaning the system may switch on more easily and stay on for longer as people get older. Matosin, who is also a member of the Charles Perkins Centre and the Brain and Mind Centre, said the altered stress response is concentrated in the brain's frontal cortex, the region that supports memory, decision-making and emotional control.

A persistently heightened stress response may leave the frontal cortex's circuits more vulnerable to damage as the brain ages, increasing susceptibility to psychiatric illnesses such as schizophrenia later in life. The findings open up the possibility of developing new treatments that target the FKBP5 gene directly.