Psychological stress--cellular and molecular mechanisms.

Pathophysiological regulation of the stress response involves a number of complex interactions at the organismal, cellular and molecular levels. A salient feature of the stress response is the activation of the hypothalamic-pituitary-adrenal axis. Molecular studies of this phenomenon have found a number of genes which are differentially expressed in stressed individuals and control subjects. The transcription factor NF-kappaB controls many of these genes, which is evidence of the key role it plays in the cellular stress response. Stress upregulates a number of genes such as the transcription factor genes that control cell growth, chromatin structure, cell cycle activation and enzymes involved in the biosynthesis of nucleic acids and proteins. The genes that are down-regulated in stress are cell cycle inhibitors, apoptosis related genes, antiproliferative cytokines and Apo J, the NF-kappaB inhibitor. Post-traumatic stress disorder (PTSD) is an anxiety disorder which develops as a reaction to an extreme traumatic event but only in a small proportion of the population. It is still unknown what molecular mechanisms trigger its progression. Both genetic and epigenetic factors play a role in this condition. Although the environmental component is necessary for developing PTSD, it has been suggested that 30% of the variance in PTSD symptoms could be attributed to genetic influences. Utilizing genome wide association studies, it would be possible to identify new genes involved in PTSD development and elucidate the molecular pathways which are dysregulated. This will facilitate the identification of novel biomarkers that may help in PTSD diagnosis and treatment.