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A pathway phenotype linking metabolic, immune, oxidative, and opioid pathways with comorbid depression, atherosclerosis, and unstable angina

Published online by Cambridge University Press:  27 May 2021

Rana Fadhil Mousa ,
Hasan Najah Smesam ,
Hasan Abbas Qazmooz ,
Hussein Kadhem Al-Hakeim  and
Michael Maes Open the ORCID record for Michael Maes [Opens in a new window]
Rana Fadhil Mousa
Affiliation:
Faculty of Veterinary Medicine, University of Kerbala, Karbala, Iraq
Hasan Najah Smesam
Affiliation:
Department of Chemistry, College of Science, University of Kufa, Najaf, Iraq
Hasan Abbas Qazmooz
Affiliation:
Department of Ecology, College of Science, University of Kufa, Najaf, Iraq
Hussein Kadhem Al-Hakeim
Affiliation:
Department of Chemistry, College of Science, University of Kufa, Najaf, Iraq
Michael Maes*
Affiliation:
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria School of Medicine, IMPACT Strategic Research Centre, Deakin University, Geelong, Victoria, Australia
*
* Author for correspondence: Prof. Dr. Michael Maes, MD, PhD Email: dr.michaelmaes@hotmail.com
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Abstract

Background

There is strong comorbidity between atherosclerosis (ATS) and depression which is attributed to increased atherogenicity, insulin resistance (IR), and immune and oxidative stress.

Aim of the study

To examine the role of the above pathways and mu-opioid receptor (MOR), β-endorphin levels, zinc, copper, vitamin D3, calcium, and magnesium in depression due to ATS/unstable angina (UA).

Methods

Biomarkers were assayed in 58 controls and 120 ATS patients divided into those with moderate and severe depression according to the Beck Depression Inventory-II (BDI-II) scores >19 and >29, respectively.

Results

Neural network and logistic regression models showed that severe depression due to ATS/UA was best predicted by interleukin-6 (IL-6), UA, MOR, zinc, β-endorphin, calcium and magnesium, and that moderate depression was associated with IL-6, zinc, MOR, β-endorphin, UA, atherogenicity, IR, and calcium. Neural networks yielded a significant discrimination of severe and moderate depression with an area under the receiver operating curves of 0.831 and 0.931, respectively. Using Partial Least Squares path analysis, we found that 66.2% of the variance in a latent vector extracted from ATS/UA clinical features, and the BDI-II scores, atherogenicity, and IR could be explained by the regression on IL-6, IL-10, zinc, copper, calcium, MOR, and age. The BDI-II scores increased from controls to ATS to UA class III to UA class IV.

Conclusions

Immune activation, the endogenous opioid system, antioxidants, trace elements, and macrominerals modulate a common core shared by increased depressive symptoms, ATS, UA, atherogenicity, and IR.

Keywords

Unstable anginainflammationneuro-immunemajor depressionoxidative stressatherogenicity
Type
Original Research
Information
CNS Spectrums , Volume 27 , Issue 6 , December 2022 , pp. 676 - 690
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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