Estrogen enhances stress-induced prefrontal cortex dysfunction: relevance to Major Depressive Disorder in women

It is well documented that exposure to stress can precipitate or exacerbate many mental illnesses,(1,2) including major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Women are twice as likely as men to develop these disorders,(34) as well as most anxiety disorders and phobias,(5) but the biological causes of this discrepancy are poorly understood. Interestingly, there is evidence that the increased prevalence of MDD in women occurs primarily during the childbearing years, when circulating estrogen is present.(67) These observations raise questions as to whether men and women have distinct neurobiological responses to stress, and if so, how might estrogen mediate these differences? Attempts to answer these questions in animal models have generated a growing body of literature demonstrating that estrogen can, indeed, modulate the effects of stress in the brain. Moreover, these effects are demonstrable in brain regions relevant to MDD, and are consistent with the idea that estrogen might enhance the stress response, promoting a greater vulnerability to mental illness.