Stress and the brain : new challenge for psychopharmacology / Brian H. Harvey

Abstract

Anxiety and mood disorders such as panic, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD) and depression are amongst the most prevalent, disabling, and chronic of all the psychiatric disorders. Neuropsychiatric disorders comprise the second largest component of the burden of disease in South Africa. To compound the problem, under-diagnosis and current treatments that are in most cases less than adequately effective, contributes to an enormous personal and economic cost to the patient and his/her family. Recent brain imaging studies in PTSD and depression have emphasized that these illnesses may induce damaging effects on regions of the brain involved in regulating the response to stress. While controversy prevails as to whether these changes represent an adaptive process or are indeed pathological they are associated with marked changes in memory and other cognitive functions. In depression, a history of prior episodes are correlated with a higher risk of relapse, while poor compliance with antidepressants not only predicts later relapse, it may result in a more shrinkage of the above-mentioned brain regions. Perhaps the structural change caused by prolonged depressive illness explains why recurrent episodes are less responsive to treatment. Similarly, even with the introduction of effective medications for PTSD, many patients remain treatment-resistant. However, does stress damage the brain and if so, are the mechanisms and prompts for its induction different for these disorders? Clearly, understanding their pathological basis will assist in developing more effective treatment strategies. This paper will highlight at least one potential new avenue for future psychotropic drug research in depression and anxiety disorders, viz. the glutamate-nitric oxide-cGMP pathway.