Not surprisingly, PTSD patients show substantial amygdala activation to stimuli related to the events that caused the disorder. Thus, combat veterans with PTSD show Pfizer Licensed Compound Library in vitro exaggerated amygdala activation to war scenes, relative to non-PTSD controls.48 Interestingly,
they also show exaggerated amygdala activity to fear stimuli unrelated to combat, such as fearful faces.49 However, PTSD patients have reduced mPFC activity in response to these stimuli,48-50 and this often correlates with the degree of disorder. It is possible that there is exaggerated amygdala activation in PTSD because there has been a loss of mPFC inhibition Inhibitors,research,lifescience,medical of the amygdala. Many of the events that induce PTSD are ones over which the individual has little behavioral control Not all of the individuals who experience these events develop PTSD, and it may be that earlier experiences with control or other forms of coping protect against the development of the disorder by biasing the mPFC to respond actively, thereby maintaining inhibition Inhibitors,research,lifescience,medical of the amygdala, and perhaps other stress-responsive structures. Selected abbreviations and acronyms Inhibitors,research,lifescience,medical 5-HT serotonin CE central nucleus of amygdala CS conditioned
stimulus DRN dorsal raphe nucleus ES escapable shock IS inescapable shock LC locus coeruleus mPFCv medial prefrontal Inhibitors,research,lifescience,medical cortex mPFC ventral medial prefrontal cortex PTSD post-traumatic stress disorder US unconditioned stimulus
Recent advances In molecular
genetics have stimulated basic and clinical research, and opened up access to hypothesis-driven and unbiased genetic approaches. With knowledge of the genes Involved in complex basic functions like the stress response, and of multifactorial diseases like stress-related disorders, we can Improve our understanding of the mechanisms and moderators Involved In the biology Inhibitors,research,lifescience,medical of normal and altered stress response, which In turn will help to Identify new drug targets and Interventions for stress-related disorders. Stress response and stress-related disorders Though there is no generally accepted definition, stress Is usually Linifanib (ABT-869) defined as a state of disturbed homeostasis evoking a multiplicity of somatic and mental adaptive reactions, which are summarized as stress response aiming to reconstitute the initial homeostasis or allostasis,1 ie, a new level of homeostasis after successful adaptation.2 The pioneer of stress research, Hans Selye, claimed a stimulus-independent nonspeciflcity of the stress response3,4 which has been criticized by others.1,5,6 Nevertheless, different kinds of stressors, physical and psychosocial, lead equivocally to a rapid activation of the sympathetic nervous system followed by a stimulation of the hypothalamlc-pitultary-adrenocortical (HPA) axis.