Association of posttraumatic stress disorder with reduced in vivo norepinephrine transporter availability in the locus coeruleus

JAMA Psychiatry. 2013 Nov;70(11):1199-1205. doi: 10.1001/jamapsychiatry.2013.399.

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.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Carbon Isotopes
  • Case-Control Studies
  • Female
  • Functional Neuroimaging
  • Humans
  • Locus Coeruleus / diagnostic imaging
  • Locus Coeruleus / metabolism*
  • Male
  • Morpholines
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism*
  • Radionuclide Imaging
  • Reboxetine
  • Severity of Illness Index
  • Stress Disorders, Post-Traumatic / diagnostic imaging
  • Stress Disorders, Post-Traumatic / metabolism*
  • Wounds and Injuries / metabolism

Substances

  • Carbon Isotopes
  • Morpholines
  • Norepinephrine Plasma Membrane Transport Proteins
  • O-methyl reboxetine
  • Reboxetine