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Original Investigation |

Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus

Robert H. Pietrzak, PhD, MPH1,2; Jean-Dominique Gallezot, PhD3; Yu-Shin Ding, PhD4; Shannan Henry, BS3; Marc N. Potenza, MD, PhD2; Steven M. Southwick, MD1,2; John H. Krystal, MD1,2; Richard E. Carson, PhD3; Alexander Neumeister, MD4,5
[+] Author Affiliations
1Clinical Neurosciences Division, National Center for Posttraumatic Stress Disorder, Veterans Affairs Connecticut Healthcare System, West Haven
2Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
3Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut
4Departments of Psychiatry and Radiology, New York University School of Medicine, New York
5Steven 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
JAMA Psychiatry. 2013;70(11):1199-1205. doi:10.1001/jamapsychiatry.2013.399.
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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.

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Figures

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Figure 1.
Positron Emission Tomography Images of Norepinephrine Transporter Availability in the Locus Coeruleus of Participants in the Study Groups

Three representative participants were chosen with binding potential (BPND) values similar to the mean of each study group. Positron emission tomography images are in Montreal Neurological Institute space. HC indicates healthy adults; PTSD, adults exposed to trauma who developed posttraumatic stress disorder; and TC, adults exposed to trauma who did not develop posttraumatic stress disorder.

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Figure 2.
Scatterplot of the Association Between Standardized (S,S)-[11C]O-methylreboxetine BPND Values in the Locus Coeruleus and Anxious Arousal Symptoms Among Individuals With Posttraumatic Stress Disorder

Values represent SDs; dashed lines represent 95% CIs. BPND indicates binding potential.

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