Editorial [Hot Topic: How Brain Faces Stressors, Regulates Stress Response and Undergoes Stress Consequences (Guest Editor: Juan C. Leza)]

Stress scientists cross the line between physiology and pathology, trying to understand the broad physiological responses of stress that can convert to pathology, depending on the coping ability of the organism, under conditions of extreme intensity and/or long duration. These “pathological” changes are sometimes reversible without treatment. The tremendous intellectual challenge for understanding the basis of this response has generated new and exciting data on the possibility to treat or prevent some CNS diseases ranging from depression to Alzheimer. In this volume of CDT-CNS, experts in the field address different aspects of the effects of stress on brain function, including a discussion of whether the consequences of stress are permanent or not, if it can provoke or predispose humans to diseases such as depression, drug abuse or others, and the molecular basis of the brain damage. Antonio Armario begins with the most important question: What is stress? People use the term stress in a broad sense, synonymous with scare -more or less prolonged, preoccupations from a variety of origins or overload of work. The consequences of stress were described in Selye's seminal paper in 1936: A syndrome produced by diverse nocuous agents [1]. However, after 70 years, the definition of stress remains to be a subject of debate. In biological systems, the classical definition is that stress is condition that seriously perturbs the physiological/psychological homeostasis of an organism. Indeed, biological stress occurs every day to organisms in their relation with other organisms and also with themselves, provoking a double-faced response: it can be an adaptive mechanism, allowing the organism to survive or fight the stressful experience, but stress also has a negative impact on the individual, mainly after very intense, long lasting stressful stimuli. These consequences might be a direct neuropsychopathology or vulnerability to diseases. Current terminology distinguishes between the stimulus (stressful stimulus or stressor), the state generated in the organism (stress) and the response to the situation (stress response). In the broadest sense, as initially defined by Selye, a stressor is any stimulus able to alter homeostasis [1], the term coined by Cannon, to refer to the mechanisms that allow the organisms to adapt to the challenges and to maintain critical biological parameters for survival. Several decades after, McEwen [2] extended the term of homeostasis to explain that these mechanisms of stability are continuously changing and called it allostasis. The price the organisms pay to maintain (or try to maintain) the stability is called allostatic load. The development of stress-induced permanent changes depends on factors such as chronicity, controllability, predictability and habituation, in part because they are influencing the way an organism can reduce the impact of stressors (coping strategies). This first article of this volume also raises other important points about the two different kinds of physiological responses to a stimulus: (i) a specific response to the particular stimulus, not related to its stressful properties; and (ii) a nonspecific response, common to all stressful stimuli. Therefore, the physiological response that one evaluates in a particular situation is the sum of both the specific and the non-specific responses. Furthermore, it is necessary to distinguish between the term stress marker, indicating that a particular variable is sensitive to stress, and the term marker of stress intensity, that refers to the fact that the magnitude of a particular variable is proportional to the intensity of the stressor. There are a number of stress markers, but only a few reasonably good indices of stress intensity: increases in plasma levels of catecholamines (particularly adrenaline), glucose, prolactin and HPA hormones, and a reduction of food intake. Work from the studies reviewed by Douglas Bremner in his paper and, of course, the studies from his lab demonstrates that stress leads to damage to the hippocampus in human subjects, as determined by neuroimaging techniques [3,4]. There is a percentage of the population affected with traumatic stress, who develop mental disorders, including posttraumatic stress disorder (PTSD), depression, drug abuse, dissociation, anxiety and borderline personality disorder. Based on the high overlap amongst these stress-related disorders, Bremner argues that they should be considered together as “traumaspectrum disorders” [5]. In 1995, he and his colleagues carried out the first study in PTSD patients using magnetic resonance imaging (MRI) to measure the volume of the hippocampus [4]. This study showed an 8% decrease in MRI-based measurement of right hippocampal volume in patients with combat-related PTSD in comparison to matched controls.....