Acute or Chronic? A Stressful Question

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.