Do genes dictate our risk of becoming ill?

Neuroscientists discover genetic variants that affect our stress response

Stress and traumatic experiences are the strongest risk factors for psychiatric disorders. However, our genes also influence how we react to our environment and how effectively we cope with stressful events. In a recent study, scientists at the Max Planck Institute of Psychiatry in Munich discovered genetic variants that control how cells react to stress hormones and possibly influence our individual risk of developing psychiatric disorders.

Scientists from the research group of Elisabeth Binder, Director of the Max Planck Institute of Psychiatry in Munich, aimed to identify genetic factors that are associated with stress and the risk of developing psychiatric disorders such as depression or schizophrenia. Using blood cells they investigated genetic variants that are frequently detected in the general population. “Firstly, we determined which of the approximately 2 million genetic variants particularly influence the cellular response to stress hormones. We found more than 3,000,” states Janine Arloth, bioinformatician and first author of the current study. “Then we discovered that 282 of them additionally correlate with the risk of developing depression and to some extent schizophrenia.” Both disorders can be induced or intensified by stress and these specific genetic variants might render an individual more sensitive to stress and traumatic experiences.

In further experiments, the scientists demonstrated that the variants change the way in which humans perceive stimuli. In healthy subjects carrying several of these 282 risk variants, a central area of the brain that is associated with fear – the amygdala – overreacts to stimuli that are only slightly or not at all threatening. Such a hyper-reaction of the “fear centre” has been observed in other studies in humans suffering from depression and might therefore be a risk factor for this disorder.

“Genetic variants regulating the cellular stress response at a molecular level seem to influence our brain’s reaction to threats and thus the risk of developing psychiatric disorders,” summarizes Elisabeth Binder. “Hopefully, a better understanding of the molecular factors modifying our vulnerability to stress will help to develop better strategies for the prevention and treatment of psychiatric disorders.”

In a follow-up study the scientists plan to test whether any of the 282 genetic variants and the resulting molecular changes in the cells could serve as risk markers to identify high-risk patients at an early stage. By using targeted measures, they hope to prevent the onset of psychiatric disorders or alleviate the symptoms.

EB/AN