People who are under stress have an increased risk of a variety of mental health problems. But not everyone who experiences stressful events develops issues like post-traumatic stress disorder, depression, or substance abuse, for example. It's thought that small changes in genes, or variants, also play a role in whether or not people will experience psychiatric disorders after they are exposed to stress. A new study reported in the Proceedings of the National Academy of Sciences has provided new insight into the molecular influences underlying the response to stress by analyzing over 3,600 gene variants.
In this work, many genetic variants were assessed simultaneously to reveal more about their cooridinated effects in the brain. The scientists found genetic variants in regulatory portions of the genome; they can alter the activity of different genes. In this case, those variants affect the physiological response to glucocorticoids, a group of hormones that are related to stress.
Dexamethasone is a drug that mimics the effects of the stress hormone known as cortisol. The investigators exposed cells that respond to stress to dexamethasone, and found 79 genetic variants in the DNA of those cells that influence gene expression, but only during dexamethasone exposure. Some of these variants were related to the risk of mental health disorders. Genes, therefore, can change how sensitive people are to the impact of stress, and whether or not stress causes other psychiatric disorders, the study suggested.
The research also explored the impact of these variants when they occur together. When an individual carried more of these variants, and that person was subjected to a stressful task, the scientists found that cortisol levels were more likely to be higher in this individual compared to others without the variant combination. Baseline levels before stressful tasks were not found to be higher, so these variants only seem to be involved when stressful situations happen.
People that carried more of these genetic variants related to stress and mental health disorders also had more intense reactions to being startled.
"Genetics have an effect on the sensitivity to the consequences of stress. This molecular mechanism could explain why stressful life events correlate more or less with psychiatric disorders," noted the Director of the Max Planck Institute of Psychiatry, Elisabeth Binder.
This study might help predict who is more likely to have long term problems due to stress, and potentially help prevent that from happening or provide better treatments if it does.
Sources: Max Planck Society, Proceedings of the National Academy of Sciences (PNAS)
