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) play a key role in SCZ and treatment resistant SCZ. There are only few data on immune and endogenous opioid system (EOS) interactions in SCZ and treatment resistant SCZ.Aim of the study: 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.

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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 ◽

10.3390/diagnostics10090633 ◽

2020 ◽

Vol 10 (9) ◽

pp. 633 ◽

Cited By ~ 1

Author(s):

Shatha Rouf Moustafa ◽

Khalid F. Al-Rawi ◽

Drozdstoi Stoyanov ◽

Arafat Hussein Al-Dujaili ◽

Thitiporn Supasitthumrong ◽

...

Keyword(s):

Negative Symptoms ◽

Psychomotor Retardation ◽

Opioid System ◽

Response To Treatment ◽

Treatment Resistant ◽

Endogenous Opioid System ◽

Endogenous Opioid ◽

Symptom Dimensions ◽

Neurocognitive Impairments ◽

Thought Disorders

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.

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Plasma Beta-Endorphin Concentrations in People with Learning Disability and Self-Injurious and/or Autistic Behaviour

The British Journal of Psychiatry ◽

10.1192/bjp.168.1.105 ◽

1996 ◽

Vol 168 (1) ◽

pp. 105-109 ◽

Cited By ~ 16

Author(s):

Sophie H. N. Willemsen-Swinkels ◽

Jan K. Buitelaar ◽

Florence G. Weijnen ◽

Jos H. H. Thijssen ◽

Herman Van Engeland

Keyword(s):

Learning Disability ◽

Learning Disabled ◽

Opioid System ◽

Disabled People ◽

Endogenous Opioid System ◽

Endogenous Opioid ◽

Beta Endorphin ◽

Functional Disturbances ◽

Autistic Behaviour ◽

Opioid Systems

BackgroundIt has been suggested that the key variable in reduced plasma immunoreactive β-endorphin concentrations in autistic subjects may be concomitant self-injurious behaviour.MethodWe studied morning levels of plasma β-endorphin in 33 learning disabled people with self-injurious and/or autistic behaviour.ResultsThe β-endorphin level of the subjects with severe self-injurious behaviour proved to be significantly lower than that of autistic subjects without severe self-injurious behaviour (3.6 (1.4) pmol/l v. 5.8 (4.3) pmol/l; t-test: P = 0.045. Replication: 3.7 (1.1) pmol/l v. 5.7 (3.8) pmol/l; t-test P = 0.043). Individuals with mild and occasional self-injurious behaviour were found to have β-endorphin levels comparable to those without self-injurious behaviour. Further, subjects being treated with neuroleptics had lower β-endorphin levels than untreated subjects.ConclusionsThese results stress that in any study of opioid systems of learning disabled people, it is very important to differentiate between people with and without severe self-injurious behaviour. The results support the idea that severe self-injurious behaviour may be related to functional disturbances in the endogenous opioid system.

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Faculty Opinions recommendation of Interface of physical and emotional stress regulation through the endogenous opioid system and mu-opioid receptors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1047297.793505805 ◽

2015 ◽

Author(s):

Rita Valentino

Keyword(s):

Emotional Stress ◽

Opioid Receptors ◽

Opioid System ◽

Mu Opioid Receptors ◽

Endogenous Opioid System ◽

Endogenous Opioid ◽

Stress Regulation ◽

Mu Opioid

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Trace Element, Immune and Opioid Biomarkers of Unstable Angina, Increased Atherogenicity and Insulin Resistance: Results of Machine Learning

10.20944/preprints202007.0260.v1 ◽

2020 ◽

Author(s):

Hassan Abbas Qazmooz ◽

Hassan Najah Smeism ◽

Rana Fadhil Mousa ◽

Hussein Kadhem Al-Hakeim ◽

Michael Maes

Keyword(s):

Insulin Resistance ◽

Trace Elements ◽

Trace Element ◽

Unstable Angina ◽

Vitamin D3 ◽

Opioid System ◽

Healthy Controls ◽

Endogenous Opioid System ◽

Endogenous Opioid ◽

Beta Endorphin

Background: Aberrations in endothelial cells, immune and oxidative pathways are associated with atherosclerosis (ATS) and unstable angina (UA). The role of trace elements, minerals, and the endogenous opioid system (EOS) in UA are less well established. Methods: We measured lipid, insulin resistance (IR), and immune, trace element (copper and zinc), mineral (magnesium, calcium), EOS (β-endorphin and mu-opioid receptor (MOR)) and antioxidant (vitamin D3) biomarkers in patients with ATS (n=60) and UA (n=60) and healthy controls (n=58). Results: ATS patients showed increased atherogenic and IR indices, IL-6, IL-10, β-endorphin, copper and magnesium, and lower zinc than healthy controls. Logistic regression showed that UA was significantly discriminated from ATS without UA with an accuracy of 85.5% using calcium, IL-10, β-endorphin, MOR, triglycerides, IR (all positively), and copper and vitamin D3 (inversely). Neural networks showed that UA was discriminated from ATS without UA with an area under the ROC curve of 0.942 using MOR, β-endorphin, calcium, insulin resistance, vitamin D3 and copper as input variables. We found that 50.0% of the variance in IR was explained by the regression on copper, IL-10, IL-6 (all positively), and zinc (inversely), while 32.9% of the variance in the atherogenic index of plasma was explained by copper, IL-10 (both positively), and magnesium (inversely). Conclusion: UA is not only mediated by insulin resistance, atherogenicity, and immune disorders, but also by aberrations in the endogenous opioid system and trace elements as well as lowered antioxidant levels. Copper appears to play a key role in IR and atherogenicity.

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