The scientists also conducted a genetic experiment which showed that, in resistant mice, many more genes in the VTA than in the NAc went into action in stressful situations, compared with vulnerable mice. Gene activity governs a host of biochemical events in the brain, and the results of this experiment suggest that genes in the VTA of resilient mice are working hard to offset mechanisms that promote vulnerability.
Another component of the study revealed that mice with a naturally occurring variation in part of the gene that produces the BDNF protein are resistant to stress. The variation results in lower production of BDNF, consistent with the finding that low BDNF activity promotes resilience.
The scientists also examined brain tissue of deceased people with a history of depression, and compared it with brain tissue of mice that showed vulnerability to stress. In both cases, the researchers found higher-than-average BDNF protein in the brain's reward areas, offering a potential biological explanation of the link between stress and depression.
"The fact that we could increase these animals' ability to adapt to stress by blocking BDNF and its signals means that it may be possible to develop compounds that improve resilience. This is a great opportunity to explore potential ways of increasing stress-resistance in people faced with situations that might otherwise result in post-traumatic stress disorder, for example... But it doesn't happen in a vacuum. Blocking BDNF at certain stages in the process could perturb other systems in negative ways. The key is to identify safe ways of enhancing this protective resilience machinery" said Nestler.2
Implications and summary:
Identifying why some people are more resilient to stress than others -- why it plays such a role in the development of mental illnesses such as depression and PTSD for those who are not resilient -- may well be the key to both preventing those mental illnesses in some people and in providing better treatments. This is absolutely an area in which more research is needed.
