Mu opioid receptor availability in people with psychiatric disorders who died by suicide: a case control study

Abstract

BackgroundMu opioid receptors have previously been shown to be altered in people with affective disorders who died as a result of suicide. We wished to determine whether these changes were more widespread and independent of psychiatric diagnoses.MethodsMu receptor levels were determined using [3 H]DAMGO binding in BA24 from 51 control subjects; 38 people with schizophrenia (12 suicides); 20 people with major depressive disorder (15 suicides); 13 people with bipolar disorder (5 suicides) and 9 people who had no history of psychiatric disorders but who died as a result of suicide. Mu receptor levels were further determined in BA9 and caudate-putamen from 38 people with schizophrenia and 20 control subjects using [3 H]DAMGO binding and, in all three regions, using Western blots. Data was analysed using one-way ANOVAs with Bonferroni’s Multiple Comparison Test or, where data either didn’t approximate to a binomial distribution or the sample size was too small to determine distribution, a Kruskal-Wallis test with Dunn’s Multiple Comparison Test.Results[3 H]DAMGO binding density was lower in people who had died as a result of suicide (p<0.01). People with schizophrenia who had died as a result of suicide had lower binding than control subjects (p<0.001), whilst people with bipolar disorder (non- suicide) had higher levels of binding (p<0.05). [3 H]DAMGO binding densities, but not mu protein levels, were significantly decreased in BA9 from people with schizophrenia who died as a result of suicide (p<0.01).ConclusionsOverall these data suggest that mu opioid receptor availability is decreased in the brains of people with schizophrenia who died as a result of suicide, which would be consistent with increased levels of endogenous ligands occupying these receptors.

Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: Implications for clinical use and policy

“…[ 11 C]-carfentanil PET studies have also demonstrated higher μOR availability among recently abstinent alcohol-dependent individuals than controls (Heinz et al, 2005; Weerts et al, 2011). The studies reviewed here also excluded individuals with psychiatric problems including depressive, psychotic, or anxiety disorders, which have been found to affect μOR availability (Naber et al, 1981; Gross-Isseroff et al, 1990; Kennedy et al, 2006; Prossin et al, 2010; Scarr et al, 2012). …”

Opioid system and human emotions

“…Post‐mortem measurements of μ receptor binding in suicide victims have yielded mixed results, with some studies finding higher binding (Gross‐Isseroff et al, ; Gabilondo et al, ), some lower binding (Scarr et al, ) and some no difference at all (Zalsman et al, ). There are only two in vivo studies of μ receptor availability in depression.…”

Decreased expression of nociceptin/orphanin FQ in the dorsal anterior cingulate cortex of suicides

“…Previous post-mortem and imaging studies suggested that adaptations at the level of mu (Gabilondo et al, 1995; Gross-Isseroff et al, 1990; Kennedy et al, 2006; Scarr et al, 2012) or kappa (Hurd, 2002; Pietrzak et al, 2014) opioid receptors signaling may contribute to suicide pathophysiology. Extending on these findings, the present study shows that suicide completers exhibit decreased levels of N/OFQ mRNA in the dACC, compared to non-suicidal control subjects.…”