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In major depression, increased kappa and mu opioid receptor levels are associated with immune activation

Published online by Cambridge University Press:  14 January 2020

Hussein Kadhem Al-Hakeim ,
Suhaer Zeki Al-Fadhel ,
Arafat Hussein Al-Dujaili  and
Michael Maes Open the ORCID record for Michael Maes [Opens in a new window]
Hussein Kadhem Al-Hakeim
Affiliation:
Department of Chemistry, College of Science, University of Kufa, Kufa, Iraq
Suhaer Zeki Al-Fadhel
Affiliation:
Department of Clinical Laboratory Sciences, College of Pharmacy, University of Kufa, Kufa, Iraq
Arafat Hussein Al-Dujaili
Affiliation:
Faculty of Medicine, University of Kufa, Kufa, Iraq
Michael Maes*
Affiliation:
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Department of Psychiatry, Medical University Plovdiv, Plovdiv, Bulgaria IMPACT Research Center, Deakin University, Geelong, Australia
*
Author for correspondence: Michael Maes, Email: [email protected]
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Abstract

Objective:

This study was carried out to delineate differences between major depressive disorder (MDD) and healthy controls in dynorphin and kappa opioid receptor (KOR) levels in association with changes in the β-endorphin – mu opioid receptor (MOR) and immune-inflammatory system.

Methods:

The present study examines dynorphin, KOR, β-endorphin, MOR, interleukin (IL)-6 and IL-10 in 60 drug-free male participants with MDD and 30 age-matched healthy males.

Results:

Serum dynorphin, KOR, β-endorphin and MOR are significantly higher in MDD as compared to controls. The increases in the dynorphin/KOR system and β-endorphin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, β-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls with a bootstrapped (n = 2000) area under the receiver operating curve of 0.972. The dynorphin/KOR system is significantly decreased in depression with comorbid nicotine dependence.

Conclusion:

Our findings suggest that, in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and β-endorphin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by (a) exerting immune-regulatory activities attenuating the primary immune response and (b) modulating reward responses and mood as well as emotional and behavioural responses to stress.

Keywords

depressioncytokinesneuro-immuneendorphinopioid receptor
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 32 , Issue 2 , April 2020 , pp. 99 - 108
Copyright
© Scandinavian College of Neuropsychopharmacology 2020

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