It won't come as news to most multitasking female employees, wives and mothers, but Hebrew University and Herzog Memorial Hospital researchers have found evidence that women cope better under strain than men - as do some people of either sex with certain genetic advantages. Some people appear to be resilient to difficult conditions, whereas others react badly to such challenges, developing a range of physical and mental disorders. Much research has already shown that the way in which the brain and body adapt to acute and chronic stress is critical for physical and mental health. In fact, a recent report by the World Health Organization found that in the next two decades, stress will be the second leading cause of death. It is generally believed that the genetic code plays a prominent role in response to stress. It has been estimated that the heredity factor determines by some 62 percent the level of the stress hormone cortisol in the bloodstream. However, only a handful of studies have so far documented the role of specific genetic variants on shaping the stress response among individuals. In an effort to reveal a genetic basis for coping with stress, psychology doctoral student Idan Shalev, Prof. Richard Ebstein and Dr. Marsha Kaitz devised a laboratory-based social stress test for students, and published their results recently in the online version of the journal Psychoneuroendocrinology. In the test, the researchers examined the amount of cortisol in the saliva of 97 university students via the Trier Social Stress Test (TSST); this was devised at Germany's Trier University and measures changes in salivary cortisol to assess the stress response to challenging social situations. The students were told that they would play the role of a job interviewee and had five minutes to persuade the interviewers to hire them. It was carried out with a microphone and camera in front of a panel of three somber judges. In the second phase of the interview, subjects were tested in a mental arithmetic task in which they were asked to count backwards and out loud from 1,687 in multiples of 13 as quickly and accurately as possible. If the subject made a mistake he or she was asked to start the series again. The researchers not only tested their saliva for cortisol, but also took mouthwash samples and tested the students as to whether they carried a brain-derived neurotrophic factor (BDNF) gene, which is involved in supporting the growth and differentiation of brain cells. Importantly, animal studies show that BDNF expression is reduced in chronic stress and restored by antidepressant treatment. The BDNF gene is characterized by a variant that codes for either the valine (Val) or methionine (Met) amino acids. Individuals carry two of each gene, with the Val variant being more common. In the study, subjects carrying two copies of the VAL variant (Val/Val), were compared in their cortisol response to those carrying one copy of the Val and one of the Met (Val/Met). When looking at the responses of the subjects in the stress testing, the researchers found that the Val/Met men and women carriers had nearly equal cortisol levels. However, men with the Val/Val variant had a higher cortisol response (and therefore a higher reaction to social stress) than the men carrying the Val/Met variant. As for women, surprisingly, the opposite was found: the Val/Val women had a lower cortisol response than the Val/Met women. Why the Val/Val variant produces opposite stress reactions in men and women remains a puzzle. Because of the predominance of the Val/Val type for both sexes, the males showed overall greater stress in the testing than the females. The researchers say their investigation shows the importance of genotyping as an aid in helping to resolve paradoxical observations related to stress-related sex differences. They said it also provides new insight into how depression and other psycho-neurological illnesses may be the result of a combination of stressful life events and genetic factors.