Data-driven analysis of kappa opioid receptor binding in major depressive disorder measured by positron emission tomography
Year: 2021
Type: article
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 [ 11 C]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, V T ) 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 [ 11 C]GR103545 V T 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.
Source: Translational Psychiatry
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,380
Awards: G1044130170, G1326316569, G1446319095, G1903722027, G2002323707, Brief Research In Aging and Interdisciplinary Neurosciences (BRAIN), G244163181, G2776647444, Novel Mechanisms Underlying Depression: PET Imaging of the Kappa Opioid Receptor, G444762953, G6049908716, G6633541147, G6897685743, G7025399989, Multimodal Neuroimaging of Alcohol Withdrawal: The Role of Glutamate in Neural Reorganization, G8022799352, Clinical and Translational Science Award, G8492761622, G9000042960, G9000303460, Yale Clinical and Translational Science Award
OpenAlex ID: W3214899326