Unique and joint associations of polygenic risk for major depression and opioid use disorder with endogenous opioid system function.

Autor: Love T; Department of Psychiatry, University of Utah & Huntsman Mental Health Institute, Salt Lake City, UT, 84112, USA., Shabalin AA; Department of Psychiatry, University of Utah & Huntsman Mental Health Institute, Salt Lake City, UT, 84112, USA., Kember RL; Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania and Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA, 19104, USA., Docherty AR; Department of Psychiatry, University of Utah & Huntsman Mental Health Institute, Salt Lake City, UT, 84112, USA.; Virginia Institute for Psychiatric & Behavioral Genetics and Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, 23291, USA., Zhou H; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA.; West Haven Veterans Affairs Medical Center, West Haven, CT, 06516, USA., Koppelmans V; Department of Psychiatry, University of Utah & Huntsman Mental Health Institute, Salt Lake City, UT, 84112, USA., Gelernter J; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA.; West Haven Veterans Affairs Medical Center, West Haven, CT, 06516, USA., Baker AK; Department of Psychiatry, University of Utah & Huntsman Mental Health Institute, Salt Lake City, UT, 84112, USA.; Department of Anesthesiology, Duke University School of Medicine, Durham, NC, 27701, USA., Hartwell E; Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania and Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA, 19104, USA., Dubroff J; Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA., Zubieta JK; Department of Psychiatry, Northwell Health, John T. Mather Memorial Hospital, Port Jefferson, NY, 11777, USA. jzubieta1@northwell.edu., Kranzler HR; Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania and Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA, 19104, USA. kranzler@pennmedicine.upenn.edu.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2022 Sep; Vol. 47 (10), pp. 1784-1790. Date of Electronic Publication: 2022 May 11.
DOI: 10.1038/s41386-022-01325-1
Abstrakt: Major depressive disorder (MDD) and opioid use disorder (OUD) are common, potentially fatal, polygenic disorders that are moderately heritable and often co-occur. We examined the unique and shared associations of polygenic risk scores (PRS) for these disorders with µ-opioid receptor (MOR) concentration and endogenous opioid response during a stressful stimulus. Participants were 144 healthy European-ancestry (EA) subjects (88 females) who underwent MOR quantification scans with [ 11 C]carfentanil and PET and provided DNA for genotyping. MOR non-displaceable binding potential (BP ND ) was measured in 5 regions of interest (ROIs) related to mood and addiction. We examined associations of PRS both at baseline and following opioid release calculated as the ratio of baseline and stress-challenge scans, first in the entire sample and then separately by sex. MOR availability at baseline was positively associated with MDD PRS in the amygdala and ventral pallidum. MDD and OUD PRS were significantly associated with stress-induced opioid system activation in multiple ROIs, accounting for up to 14.5% and 5.4%, respectively, of the variance in regional activation. The associations were most robust among females, where combined they accounted for up to 25.0% of the variance among the ROIs. We conclude that there is a pathophysiologic link between polygenic risk for MDD and OUD and opioid system activity, as evidenced by PRS with unique and overlapping regional associations with this neurotransmitter system. This link could help to explain the high rate of comorbidity of MDD and OUD and suggests that opioid-modulating interventions could be useful in treating MDD and OUD, both individually and jointly.
(© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)
Databáze: MEDLINE
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