Altered central μ-opioid receptor binding after psychological trauma

Background: Functional neuroimaging studies have detected abnormal limbic and paralimbic activation to emotional probes in posttraumatic stress disorder (PTSD), but few studies have examined neurochemical mechanisms that underlie functional alterations in regional cerebral blood flow. The mu-opioid neurotransmitter system, implicated in responses to stress and suppression of pain, is distributed in and is thought to regulate the function of brain regions that are implicated in affective processing. Methods: Here we examined the mu-opioid system with positron emission tomography and the mu-opioid receptor-selective radiotracer [C-11] carfentanil in 16 male patients with PTSD and two non-PTSD male control groups, with (n=14) and without combat exposure (n=15). Differences in R-opioid receptor binding potential (BP2) were detected within discrete limbic and paralimbic regions. Results: Relative to healthy controls, both trauma-exposed groups had lower R-opioid receptor BP2 in extended amygdala, nucleus accumbens, and dorsal frontal and insular cortex but had higher BP2 in the orbitofrontal cortex. PTSD patients exhibited reduced BP2 in anterior cingulate cortex compared with both control groups. mu-Opioid receptor BP2 in combat-exposed subjects without PTSD was lower in the amygdala but higher in the orbitofrontal cortex compared with both PTSD patients and healthy controls. Conclusions: These findings differentiate the general response of the mu-opioid system to trauma from more specific changes associated with PTSD.