The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and κ and μ Opioid Receptors Are Associated with Interleukin-6
Background: activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS) plays a key role in schizophrenia (SCZ) and treatment resistant SCZ. There are only a few data on immune and endogenous opioid system (EOS) interactions in SCZ and treatment r...
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MDPI AG
2020-08-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/10/9/633 |
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| author | Shatha Rouf Moustafa Khalid F. Al-Rawi Drozdstoi Stoyanov Arafat Hussein Al-Dujaili Thitiporn Supasitthumrong Hussein Kadhem Al-Hakeim Michael Maes |
| author_facet | Shatha Rouf Moustafa Khalid F. Al-Rawi Drozdstoi Stoyanov Arafat Hussein Al-Dujaili Thitiporn Supasitthumrong Hussein Kadhem Al-Hakeim Michael Maes |
| author_sort | Shatha Rouf Moustafa |
| collection | DOAJ |
| description | Background: activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS) plays a key role in schizophrenia (SCZ) and treatment resistant SCZ. There are only a few data on immune and endogenous opioid system (EOS) interactions in SCZ and treatment resistant SCZ. Methods: we examined serum β-endorphin, endomorphin-2 (EM2), mu-opioid (MOR) and kappa-opioid (KOR) receptors, and interleukin (IL)-6 and IL-10 in 60 non responders to treatment (NRTT), 55 partial RTT (PRTT) and 43 normal controls. Results: serum EM2, KOR, MOR, IL-6 and IL-10 were significantly increased in SCZ as compared with controls. β-endorphin, EM2, MOR and IL-6 were significantly higher in NRTT than in PRTT. There were significant correlations between IL-6, on the one hand, and β-endorphin, EM2, KOR, and MOR, on the other, while IL-10 was significantly correlated with MOR only. A large part of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation and formal thought disorders was explained by the combined effects of EM2 and MOR with or without IL-6 while increased KOR was significantly associated with all symptom dimensions. Increased MOR, KOR, EM2 and IL-6 were also associated with neurocognitive impairments including in episodic, semantic and working memory and executive functions. Conclusion: the EOS contributes to SCZ symptomatology, neurocognitive impairments and a non-response to treatment. In SCZ, EOS peptides/receptors may exert CIRS functions, whereas increased KOR levels may contribute to the pathophysiology of SCZ and EM2 and KOR to a non-response to treatment. |
| first_indexed | 2024-03-10T16:48:17Z |
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| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T16:48:17Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-db9e7a56ac364365bddeb09be9b321782023-11-20T11:26:26ZengMDPI AGDiagnostics2075-44182020-08-0110963310.3390/diagnostics10090633The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and κ and μ Opioid Receptors Are Associated with Interleukin-6Shatha Rouf Moustafa0Khalid F. Al-Rawi1Drozdstoi Stoyanov2Arafat Hussein Al-Dujaili3Thitiporn Supasitthumrong4Hussein Kadhem Al-Hakeim5Michael Maes6Clinical Analysis Department, College of Pharmacy, Hawler Medical University, Havalan City, Erbil 44001, IraqCollege of Science, University of Anbar, Ramadi 31001, IraqDepartment of Psychiatry, Medical University of Plovdiv, Plovdiv 4000, BulgariaClinical Psychiatry, Faculty of Medicine, University of Kufa, Najaf 540011, IraqDepartment of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10110, ThailandDepartment of Chemistry, College of Science, University of Kufa, Najaf 540011, IraqDepartment of Psychiatry, Medical University of Plovdiv, Plovdiv 4000, BulgariaBackground: activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS) plays a key role in schizophrenia (SCZ) and treatment resistant SCZ. There are only a few data on immune and endogenous opioid system (EOS) interactions in SCZ and treatment resistant SCZ. Methods: we examined serum β-endorphin, endomorphin-2 (EM2), mu-opioid (MOR) and kappa-opioid (KOR) receptors, and interleukin (IL)-6 and IL-10 in 60 non responders to treatment (NRTT), 55 partial RTT (PRTT) and 43 normal controls. Results: serum EM2, KOR, MOR, IL-6 and IL-10 were significantly increased in SCZ as compared with controls. β-endorphin, EM2, MOR and IL-6 were significantly higher in NRTT than in PRTT. There were significant correlations between IL-6, on the one hand, and β-endorphin, EM2, KOR, and MOR, on the other, while IL-10 was significantly correlated with MOR only. A large part of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation and formal thought disorders was explained by the combined effects of EM2 and MOR with or without IL-6 while increased KOR was significantly associated with all symptom dimensions. Increased MOR, KOR, EM2 and IL-6 were also associated with neurocognitive impairments including in episodic, semantic and working memory and executive functions. Conclusion: the EOS contributes to SCZ symptomatology, neurocognitive impairments and a non-response to treatment. In SCZ, EOS peptides/receptors may exert CIRS functions, whereas increased KOR levels may contribute to the pathophysiology of SCZ and EM2 and KOR to a non-response to treatment.https://www.mdpi.com/2075-4418/10/9/633inflammationschizophreniatreatment resistanceneurocognitionneuroimmunomodulation |
| spellingShingle | Shatha Rouf Moustafa Khalid F. Al-Rawi Drozdstoi Stoyanov Arafat Hussein Al-Dujaili Thitiporn Supasitthumrong Hussein Kadhem Al-Hakeim Michael Maes The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and κ and μ Opioid Receptors Are Associated with Interleukin-6 Diagnostics inflammation schizophrenia treatment resistance neurocognition neuroimmunomodulation |
| title | The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and κ and μ Opioid Receptors Are Associated with Interleukin-6 |
| title_full | The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and κ and μ Opioid Receptors Are Associated with Interleukin-6 |
| title_fullStr | The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and κ and μ Opioid Receptors Are Associated with Interleukin-6 |
| title_full_unstemmed | The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and κ and μ Opioid Receptors Are Associated with Interleukin-6 |
| title_short | The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and κ and μ Opioid Receptors Are Associated with Interleukin-6 |
| title_sort | endogenous opioid system in schizophrenia and treatment resistant schizophrenia increased plasma endomorphin 2 and κ and μ opioid receptors are associated with interleukin 6 |
| topic | inflammation schizophrenia treatment resistance neurocognition neuroimmunomodulation |
| url | https://www.mdpi.com/2075-4418/10/9/633 |
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