Elsevier

Biological Psychiatry

Volume 61, Issue 9, 1 May 2007, Pages 1030-1038
Biological Psychiatry

Original article
Altered Central μ-Opioid Receptor Binding After Psychological Trauma

https://doi.org/10.1016/j.biopsych.2006.06.021Get rights and content

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 μ-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 μ-opioid system with positron emission tomography and the μ-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 μ-opioid receptor binding potential (BP2) were detected within discrete limbic and paralimbic regions.

Results

Relative to healthy controls, both trauma-exposed groups had lower μ-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. μ-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 μ-opioid system to trauma from more specific changes associated with PTSD.

Section snippets

Participants

Forty-five male participants were recruited by using advertisements within the Veterans Affairs Hospital and clinics, local newspapers, and veterans’ organizations. Sixteen Vietnam veterans with posttraumatic stress disorder (PTSD patients; PP), 15 Vietnam veterans with prior combat exposure without PTSD (combat controls; CC), and 14 age-matched subjects without prior trauma exposure (normal controls; NC) participated in this study. PTSD and other axis I diagnoses were established according to

General

Overall, significant differences in μ-opioid receptor BP2 were detected by the ANOVA among the three groups in many of the a priori hypothesized regions: amygdala, extended amygdala, thalamus, NAc, insula, ACC, and mPFC (Table 2; Figure 1, Figure 2). Direct group comparisons identified differential, region-specific μ-opioid receptor availability (Table 3, Table 4, Table 5, Figure 1, Figure 2). Specifically, relative to healthy controls, both trauma-exposed groups had lower μ-opioid receptor BP2

Discussion

Altered function of endogenous opioids system in PTSD patients has been hypothesized elsewhere (Glover 1993, Pitman et al 1990); however, this is the first direct evidence of alterations in μ-opioid receptor in vivo availability in PTSD. We observed significant differences in regional μ-opioid receptor BP2 between the trauma-exposed groups and normal controls, as well as between PTSD patients and trauma-exposed individuals who did not develop PTSD. μ-Opioid receptor BP2 was measured in our

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