Altered central micro-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 micro-opioid system with positron emission tomography and the micro-opioid receptor-selective radiotracer [11C] 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 micro-opioid receptor binding potential (BP2) were detected within discrete limbic and paralimbic regions.


RESULTS
Relative to healthy controls, both trauma-exposed groups had lower micro-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. Micro-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 micro-opioid system to trauma from more specific changes associated with PTSD.
Liberzon
Israel
I
Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan 48109-0118, USA. liberzon@umich.edu
Taylor
Stephan F
SF
Phan
K Luan
KL
Britton
Jennifer C
JC
Fig
Lorraine M
LM
Bueller
Joshua A
JA
Koeppe
Robert A
RA
Zubieta
Jon-Kar
JK
D000222:Adaptation, Physiological / Q000502:physiology; D000328:Adult; D000679:Amygdala / Q000378:metabolism; D000701:Analgesics, Opioid / Q000493:pharmacokinetics; D002540:Cerebral Cortex / Q000378:metabolism; D005283:Fentanyl / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000378:metabolism; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000000981:diagnostic imaging / Q000378:metabolism; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism; D014728:Veterans / Q000523:psychology; D014947:Wounds and Injuries / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology*
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; C017114:carfentanil; D005283:Fentanyl