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. 2021 Nov 27;11(1):602.
doi: 10.1038/s41398-021-01729-5.

Data-driven analysis of kappa opioid receptor binding in major depressive disorder measured by positron emission tomography

Kelly Smart  1 , Ashley Yttredahl  2   3 , Maria A Oquendo  4 , J John Mann  2   3 , Ansel T Hillmer  1   5 , Richard E Carson  1 , Jeffrey M Miller  6   7
Affiliations

Data-driven analysis of kappa opioid receptor binding in major depressive disorder measured by positron emission tomography

Kelly Smart et al. Transl Psychiatry. .

Abstract

Preclinical studies have implicated kappa opioid receptors (KORs) in stress responses and depression-related behaviors, but evidence from human studies is limited. Here we present results of a secondary analysis of data acquired using positron emission tomography (PET) with the KOR radiotracer [11C]GR103545 in 10 unmedicated, currently depressed individuals with major depressive disorder (MDD; 32.6 ± 6.5 years, 5 women) and 13 healthy volunteers (34.8 ± 10 years, 6 women). Independent component analysis was performed to identify spatial patterns of coherent variance in KOR binding (tracer volume of distribution, VT) across all subjects. Expression of each component was compared between groups and relationships to symptoms were explored using the 17-item Hamilton Depression Rating Scale (HDRS). Three components of variation in KOR availability across ROIs were identified, spatially characterized by [11C]GR103545 VT in (1) bilateral frontal lobe; (2) occipital and parietal cortices, right hippocampus, and putamen; and (3) right anterior cingulate, right superior frontal gyrus and insula, coupled to negative loading in left middle cingulate. In MDD patients, component 3 was negatively associated with symptom severity on the HDRS (r = -0.85, p = 0.0021). There were no group-wise differences in expression of any component between patients and controls. These preliminary findings suggest that KOR signaling in cortical regions relevant to depression, particularly right anterior cingulate, could reflect MDD pathophysiology.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Regional patterns of source variance in [11C]GR103545 VT from ROI-level ICA.
Color bar is spatial intensity in arbitrary units.
Fig. 2
Fig. 2. Sources of variance in KOR availability associated with depressive symptom severity.
A Spatial pattern of ROI-level component 3 (R3). B Relationship between HDRS score and R3 subject loading in MDD subjects. C Spatial pattern of voxel-level component 1 (V1). D Relationship between HDRS score and V1 subject loading in MDD subjects. Color bars are spatial intensity in arbitrary units.
Fig. 3
Fig. 3. Subject loadings of components from ROI-level ICA in HC (open circles) and MDD (closed circles) subjects.
No differences in loading of any ROI-level [11C]GR103545 VT component was observed as a function of diagnosis (ps > 0.19).
Fig. 4
Fig. 4. Sources of variance in [11C]GR103545 VT from voxel-level ICA.
Color bar is spatial intensity in arbitrary units. Each row of this figure depicts component loading values for one of three components identified from voxel-level ICA analysis.
See this image and copyright information in PMC

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