We humans react to stress physically and psychologically, but not everyone is equally sensitive. While some people cope well with the consequences of stress, others suffer massively from it or even become ill. A new study shows that there may be certain genetic variants that make some people more sensitive to stress. Accordingly, these stress-regulating genes also influence the risk of developing a psychiatric disorder. This could improve the prevention of depression and the like.
Our everyday lives can be quite stressful and can sometimes throw us off track. Some people even become ill during traumatic experiences or when stress lasts for a long time. Whether or not we develop depression or another psychiatric disorder depends not only on our stress level, but also on our genes, as previous studies suggest. But which genes are specifically responsible for the fact that some people can cope well with stress and stressful life events, while others develop a psychiatric disorder in response to stress?
A research group led by Signe Penner-Goeke from the Max Planck Institute for Psychiatry (MPI) in Munich has now approached this question at the molecular level. To do this, the scientists used two human cell lines that are suitable as models for the genetic-molecular stress response and exposed them to the synthetic active ingredient dexamethasone, which mimics the effect of the natural stress hormone cortisol. They then used molecular genetic and statistical methods to investigate which genetic variants might be involved in the cellular response to stress. To do this, Penner-Goeke and her colleagues analyzed a total of 3,662 individual mutations within genetic variants in 320 gene regions that often occur in patients with psychiatric disorders.
People with a lot of “stress genes” also react more stressed
The analyzes showed that 547 of the gene variants examined were involved in a hormonally induced stress response in the cells. This type of stress-sensitive gene variant occurred in almost half of all gene regions examined. These variants were found with striking frequency at regulatory sites in the DNA - including at sites that regulate nerve cells in the brain, as the researchers report. Penner-Goeke and her colleagues conclude that some of the variants may influence the risk of developing a psychiatric disorder. “We found a number of variants that are associated with psychiatric disorders,” says Penner-Goeke.
In further experiments, the researchers examined whether the risk of psychiatric illnesses changes when such gene variants are present in combination. To do this, they subjected 183 and 171 test subjects to two different stress tasks and measured their hormone levels in their saliva and their blink reflex. In the first test, the participants were asked to solve a math problem; in the second, they were frightened. The scientists also sequenced the test subjects' DNA to determine which gene variants they had in their genome. These experiments showed that people with a higher number of stress-related gene variants had higher amounts of the stress hormone cortisol in their saliva during and shortly after the experiments and also reacted more intensely to fright. Penner-Goeke and her colleagues conclude that these gene variants influenced how violently people reacted to stressful situations.
Better prevention and treatment of psychiatric illnesses possible
“Our genes have an influence on our sensitivity to the consequences of stress,” says senior author Elisabeth Binder from the MPI, summarizing the results. This molecular mechanism could explain why stressful life events only cause psychiatric disorders in some people. Therefore, in addition to individual experiences and living conditions, genes also play a role. Further studies with other cell lines and more genetic loci still need to clarify whether the researchers have already discovered all relevant gene variants and how they trigger the cellular stress response. However, the findings can now be used to roughly predict which people have a higher risk of developing a stress-related psychiatric disorder. The knowledge could also be used for better prevention and treatment of psychiatric disorders, say the researchers.
Source: Signe Penner-Goeke (Max Planck Institute for Psychiatry) et al., PNAS, doi: 10.1073/pnas.2305773120