Acute or Chronic? A Stressful Question

摘要

Stress is a primary risk factor for neuropsychiatric disorders; at times, even a single trauma can trigger psychopathology. Many rodent models of neuropsychiatric disorders use chronic stress, measuring readouts at the end of long protocols. In a way, traditional chronic models overlook a crucial question: how does the physiological response to stressor(s) turn into a maladaptive pathway that may verge towards psychopathology? Recent evidence suggests that studying the long-term consequences of acute stress would provide critical information on the role of stress in psychopathology. This new conceptual framework could enable us to understand the determinants of a pro-adaptive versus maladaptive trajectory of stress response, and also to study the mechanism of rapid-acting antidepressants, such as ketamine, that target the glutamate system directly. Trends Stress and traumatic events are increasingly recognized as risk factors for mental disorders, in particular for depression, anxiety disorders, and post-traumatic stress disorder (PTSD). In the latter, a single trauma may determine the pathology. It is not clear how a single stressful event may induce a potentially life-long pathology. Changes in neuroarchitecture in select brain areas have been consistently found in psychiatric patients, particularly in those with depression and/or PTSD. Rodent studies with chronic stress showed similar changes as in humans. It has been suggested that the pathology-related changes (dendritic atrophy) are subsequent to an enhancement of glutamate release and excitatory transmission induced by stress, but clear evidence is still needed. Recent evidence has shown that rapid and sustained changes in neuroarchitecture are also induced by acute stress, and that the enhancement of glutamate release induced by acute stress is extended for up to at least 24 h. These lines of evidence allow the formulation of a working hypothesis, using acute stress protocols to investigate the pathophysiology of stress-related mental illnesses and the action of rapid-acting antidepressants targeting the glutamate system. ]]>