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. 2020 Oct;45(11):1953-1959.
doi: 10.1038/s41386-020-0725-9. Epub 2020 May 30.

Lowered endogenous mu-opioid receptor availability in subclinical depression and anxiety

Lauri Nummenmaa  1   2   3 , Tomi Karjalainen  4 , Janne Isojärvi  4 , Tatu Kantonen  4   5 , Jouni Tuisku  4 , Valtteri Kaasinen  4   5 , Juho Joutsa  4   5   6 , Pirjo Nuutila  4   7 , Kari Kalliokoski  4 , Jussi Hirvonen  4   8 , Jarmo Hietala  9   10 , Juha Rinne  4
Affiliations

Lowered endogenous mu-opioid receptor availability in subclinical depression and anxiety

Lauri Nummenmaa et al. Neuropsychopharmacology. 2020 Oct.

Abstract

Major depressive disorder is associated with lowered mood, anxiety, anhedonia, sleep problems, and cognitive impairments. Many of these functions are regulated by μ-opioid receptor (MOR) system. Preclinical, in vivo, and post-mortem studies have however yielded inconclusive results regarding the role of the MOR in depression and anxiety. Moreover, it is not known whether alterations in MOR are already present in subclinical depression and anxiety. In a large-scale retrospective cross-sectional study we pooled data from 135 (113 males and 22 females) healthy subjects whose brain's MOR availability was measured with positron emission tomography (PET) using an agonist radioligand [11C]carfentanil that has high affinity for MORs. Depressive and anxious symptomology was addressed with BDI-II and STAI-X questionnaires, respectively. Both anxiety and depression scores in the subclinical range were negatively associated with MOR availability in cortical and subcortical areas, notably in amygdala, hippocampus, ventral striatum, and orbitofrontal and cingulate cortices. We conclude that dysregulated MOR availability is involved in altered mood and pathophysiology of depression and anxiety disorders.

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Figures

Fig. 1
Fig. 1. Opioid receptor distribution.
Averaged map of the [11C]-carfentanil BPND images in the sample (n = 135).
Fig. 2
Fig. 2. Association between depressive and anxious symptoms and MOR.
Regions where BDI-II (top row; n = 135) and STAI-X scores (bottom row, n = 105) were associated with MOR availability. The data are thresholded at p < 0.05, FDR corrected.
Fig. 3
Fig. 3. Association between BDI-II and STAI-X scores on selected regions of interest.
The plots show least-squares regression lines with 95% confidence intervals. Statistically significant correlations are flagged with an asterisk.
Fig. 4
Fig. 4. Posterior distributions of the regression coefficients for the BDI-II and STAI-X scales.
Thick lines show 80% posterior intervals, and the lines extend until 99% posterior intervals.
See this image and copyright information in PMC

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