title: Noradrenergic dysregulation in the pathophysiology of PTSD.
abstract: A central role for noradrenergic dysregulation in the pathophysiology of post-traumatic stress disorder (PTSD) is increasingly suggested by both clinical and basic neuroscience research. Here, we integrate recent findings from clinical and animal research with the earlier literature. We first review the evidence for net upregulation of the noradrenergic system and its responsivity to stress in individuals with PTSD. Next, we trace the evidence that the α1noradrenergic receptor antagonist prazosin decreases many of the symptoms of PTSD from initial clinical observations, to case series, to randomized controlled trials. Finally, we review the basic science work that has begun to explain the mechanism for this efficacy, as well as to explore its possible limitations and areas for further advancement. We suggest a view of the noradrenergic system as a central, modifiable link in a network of interconnected stress-response systems, which also includes the amygdala and its modulation by medial prefrontal cortex. Particular attention is paid to the evidence for bidirectional signaling between noradrenaline and corticotropin-releasing factor (CRF) in coordinating these interconnected systems. The multiple different ways in which the sensitivity and reactivity of the noradrenergic system may be altered in PTSD are highlighted, as is the evidence for possible heterogeneity in the pathophysiology of PTSD between different individuals who appear clinically similar. We conclude by noting the importance moving forward of improved measures of noradrenergic functioning in clinical populations, which will allow better recognition of clinical heterogeneity and further assessment of the functional implications of different aspects of noradrenergic dysregulation.
authors.affiliation: VISN 20 Northwest Network Mental Illness Research, Education and Clinical Center (MIRECC), United States; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, United States. Electronic address: rhend@uw.edu.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Hendrickson
authors.affiliation: VISN 20 Northwest Network Mental Illness Research, Education and Clinical Center (MIRECC), United States; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, United States.
authors.forename: Murray A
authors.initials: MA
authors.lastname: Raskind
mesh_terms: D059331:Adrenergic Neurons / Q000378:metabolism*; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism*
chemical_list: D009638:Norepinephrine
keywords: Noradrenergic; Posttraumatic stress disorder (PTSD); Prazosin