Robert H Pietrzak1,2, Jean-Dominique Gallezot3, Yu-Shin Ding4, Shannan Henry3, Marc N Potenza2, Steven M Southwick1,2, John H Krystal1,2, Richard E Carson3, Alexander Neumeister4,5. 1. Clinical Neurosciences Division, National Center for Posttraumatic Stress Disorder, Veterans Affairs Connecticut Healthcare System, West Haven. 2. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. 3. Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut. 4. Departments of Psychiatry and Radiology, New York University School of Medicine, New York. 5. Steven and Alexandra Cohen Veterans Center for the Study of Posttraumatic Stress and Traumatic Brain Injury, Department of Psychiatry, New York University Langone Medical Center, New York, New York.
Abstract
IMPORTANCE: Animal data suggest that chronic stress is associated with a reduction in norepinephrine transporter (NET) availability in the locus coeruleus. However, it is unclear whether such models are relevant to posttraumatic stress disorder (PTSD), which has been linked to noradrenergic dysfunction in humans. OBJECTIVES: To use positron emission tomography and the radioligand [11C]methylreboxetine to examine in vivo NET availability in the locus coeruleus in the following 3 groups of individuals: healthy adults (HC group), adults exposed to trauma who did not develop PTSD (TC group), and adults exposed to trauma who developed PTSD (PTSD group) and to evaluate the relationship between NET availability in the locus coeruleus and a contemporary phenotypic model of PTSD symptoms. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional positron emission tomography study under resting conditions at academic and Veterans Affairs medical centers among 56 individuals in the following 3 study groups: HC (n = 18), TC (n = 16), and PTSD (n = 22). MAIN OUTCOMES AND MEASURES: The [11C]methylreboxetine-binding potential of NET availability in the locus coeruleus and the severity of PTSD symptoms assessed using the Clinician-Administered PTSD Scale. RESULTS: The PTSD group had significantly lower NET availability than the HC group (41% lower, Cohen d = 1.07). NET availability did not differ significantly between the TC and HC groups (31% difference, Cohen d = 0.79) or between the TC and PTSD groups (15% difference, Cohen d = 0.28). In the PTSD group, NET availability in the locus coeruleus was independently positively associated with the severity of anxious arousal (ie, hypervigilance) symptoms (r = 0.52) but not with any of the other PTSD symptom clusters. CONCLUSIONS AND RELEVANCE: These results suggest that PTSD is associated with significantly reduced NET availability in the locus coeruleus and that greater NET availability in this brain region is associated with increased severity of anxious arousal symptoms in individuals with PTSD.
IMPORTANCE: Animal data suggest that chronic stress is associated with a reduction in norepinephrine transporter (NET) availability in the locus coeruleus. However, it is unclear whether such models are relevant to posttraumatic stress disorder (PTSD), which has been linked to noradrenergic dysfunction in humans. OBJECTIVES: To use positron emission tomography and the radioligand [11C]methylreboxetine to examine in vivo NET availability in the locus coeruleus in the following 3 groups of individuals: healthy adults (HC group), adults exposed to trauma who did not develop PTSD (TC group), and adults exposed to trauma who developed PTSD (PTSD group) and to evaluate the relationship between NET availability in the locus coeruleus and a contemporary phenotypic model of PTSD symptoms. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional positron emission tomography study under resting conditions at academic and Veterans Affairs medical centers among 56 individuals in the following 3 study groups: HC (n = 18), TC (n = 16), and PTSD (n = 22). MAIN OUTCOMES AND MEASURES: The [11C]methylreboxetine-binding potential of NET availability in the locus coeruleus and the severity of PTSD symptoms assessed using the Clinician-Administered PTSD Scale. RESULTS: The PTSD group had significantly lower NET availability than the HC group (41% lower, Cohen d = 1.07). NET availability did not differ significantly between the TC and HC groups (31% difference, Cohen d = 0.79) or between the TC and PTSD groups (15% difference, Cohen d = 0.28). In the PTSD group, NET availability in the locus coeruleus was independently positively associated with the severity of anxious arousal (ie, hypervigilance) symptoms (r = 0.52) but not with any of the other PTSD symptom clusters. CONCLUSIONS AND RELEVANCE: These results suggest that PTSD is associated with significantly reduced NET availability in the locus coeruleus and that greater NET availability in this brain region is associated with increased severity of anxious arousal symptoms in individuals with PTSD.
Authors: N Tzourio-Mazoyer; B Landeau; D Papathanassiou; F Crivello; O Etard; N Delcroix; B Mazoyer; M Joliot Journal: Neuroimage Date: 2002-01 Impact factor: 6.556
Authors: Alan A Wilson; David Patrick Johnson; David Mozley; Doug Hussey; Nathalie Ginovart; Jose Nobrega; Armando Garcia; Jeffery Meyer; Sylvain Houle Journal: Nucl Med Biol Date: 2003-02 Impact factor: 2.408
Authors: Alexander Neumeister; Jordan Seidel; Benjamin J Ragen; Robert H Pietrzak Journal: Psychoneuroendocrinology Date: 2014-10-22 Impact factor: 4.905
Authors: Swen Hesse; Georg-Alexander Becker; Michael Rullmann; Anke Bresch; Julia Luthardt; Mohammed K Hankir; Franziska Zientek; Georg Reißig; Marianne Patt; Katrin Arelin; Donald Lobsien; Ulrich Müller; S Baldofski; Philipp M Meyer; Matthias Blüher; Mathias Fasshauer; Wiebke K Fenske; Michael Stumvoll; Anja Hilbert; Yu-Shin Ding; Osama Sabri Journal: Eur J Nucl Med Mol Imaging Date: 2017-01-09 Impact factor: 9.236
Authors: Robert H Pietrzak; Jennifer A Sumner; Allison E Aiello; Monica Uddin; Alexander Neumeister; Guia Guffanti; Karestan C Koenen Journal: J Clin Psychiatry Date: 2015-04 Impact factor: 4.384
Authors: A Frick; F Åhs; Å M Palmquist; A Pissiota; U Wallenquist; M Fernandez; M Jonasson; L Appel; Ö Frans; M Lubberink; T Furmark; L von Knorring; M Fredrikson Journal: Mol Psychiatry Date: 2015-12-01 Impact factor: 15.992