Hussein Kadhem Al-Hakeim1, Suhaer Zeki Al-Fadhel2, Arafat Hussein Al-Dujaili3, Michael Maes4,5,6. 1. Department of Chemistry, College of Science, University of Kufa, Kufa, Iraq. 2. Department of Clinical Laboratory Sciences, College of Pharmacy, University of Kufa, Kufa, Iraq. 3. Faculty of Medicine, University of Kufa, Kufa, Iraq. 4. Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 5. Department of Psychiatry, Medical University Plovdiv, Plovdiv, Bulgaria. 6. IMPACT Research Center, Deakin University, Geelong, Australia.
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.
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.
Authors: Zach J Gray; Grant S Shields; Stassja Sichko; Theresa Q Bui; Meghan Vinograd; Hector A Olvera-Alvarez; George M Slavich Journal: Compr Psychoneuroendocrinol Date: 2022-06-16
Authors: Hasan Najah Smesam; Hasan Abbas Qazmooz; Sinan Qayes Khayoon; Abbas F Almulla; Hussein Kadhem Al-Hakeim; Michael Maes Journal: J Pers Med Date: 2022-03-16