Postmortem Locus Coeruleus Neuron Count in Three American Veterans With Probable or Possible War-Related PTSD

Abstract

The authors investigated whether war-related posttraumatic stress disorder (WR-PTSD) is associated with a postmortem change in neuronal counts in the locus coeruleus (LC) since enhanced central nervous system (CNS) noradrenergic postsynaptic responsiveness has been previously shown to contribute to PTSD pathophysiology. Using postmortem neuromorphometry, the number of neurons in the right LC in seven deceased elderly male veterans was counted. Three veterans were classified as cases of probable or possible WR-PTSD. All three veterans with probable or possible WR-PTSD were found to have substantially lower LC neuronal counts compared to four comparison subjects (three nonpsychiatric veterans and one veteran with alcohol dependence and delirium tremens).To the authors’ knowledge, this case series is the first report of LC neuronal counts in patients with PTSD or any other DSM-IV-TR anxiety disorder. Previous postmortem brain tissue studies of Alzheimer’s Disease (AD) demonstrated an upregulation of NE biosynthetic capacity in surviving LC neurons. The finding reported is consistent with the similar upregulation of NE biosynthetic capacity of surviving LC neurons in veterans who developed WR-PTSD. Especially if replicated, this finding in WR-PTSD may provide further explanation of the dramatic effectiveness of propranolol and prazosin for the secondary prevention and treatment of PTSD, respectively. The LC neurons examined in this study are probably the origin of the first or second “leg” of what might be termed the PTSD candidate circuit. Larger neuromorphometric studies of the LC in veterans with WR-PTSD and in other development-stress-induced and fear-circuitry disorders are warranted, especially using VA registries.