Cerebrospinal fluid and plasma β-endorphin in combat veterans with post-traumatic stress disorder

Abstract

Opioid-mediated analgesia develops in experimental animals following traumatic stress and increased opioid-mediated analgesia has been observed in combat veterans with post-traumatic stress disorder (PTSD). These observations have led to the hypothesis that increased central nervous system (CNS) opioidergic activity exists in patients with PTSD. However, direct CNS data on opioid peptide concentrations and dynamics in patients with PTSD are lacking. We withdrew cerebrospinal fluid (CSF) via a flexible, indwelling subarachnoid catheter over a 6-h period and determined hourly CSF concentrations of immunoreactive β-endorphin (irβEND) in 10 well-characterized combat veterans with PTSD and nine matched normal volunteers. Blood was simultaneously withdrawn to obtain plasma for irβEND. PTSD symptom clusters, as measured by the CAPS, were correlated with neuroendocrine data. Mean CSF irβEND was significantly greater in patients with PTSD compared with normals and there was a negative correlation between the irβEND and PTSD intrusive and avoidant symptoms of PTSD. No intergroup difference between plasma ieβEND was found, nor was there a significant correlation between CSF and plasma irβEND. Immunoreactive β-lipotropin (irβLPH) and pro-opiomelanocortin (irPOMC), both precursors of βEND, were much more plentiful in human CSF than was β-endorphin itself, as has been previously reported. It remains to be determined whether the increased CNS opioid concentrations predate traumatic stress, thereby conferring a vulnerability to dissociative states and PTSD itself, or result from the trauma. The negative correlation between CSF irβEND and avoidant and intrusive symptoms suggests that CNS hypersecretion of opioids might constitute an adaptive response to traumatic experience. Poor correlation between CSF and plasma irβEND limits use of plasma measures to assess CNS opioid activity.