Opiate antagonists for the treatment of schizophrenia

Welch, Ellen; Thompson, Dennis F.

doi:10.1111/j.1365-2710.1994.tb00814.x

Cited by 12 publications

(7 citation statements)

References 36 publications

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“…Similarly, our novel, preliminary data on increased 3 H]DAMGO binding in BP are intriguing and deserve further investigations. Both findings add to the long held argument that the opioid system plays an important role in the pathophysiology and/or outcomes of psychiatric disorders [51]. …”

Section: Discussionsupporting

confidence: 56%

Mu opioid receptor availability in people with psychiatric disorders who died by suicide: a case control study

et al. 2012

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BackgroundMu opioid receptors have previously been shown to be altered in people with affective disorders who died as a result of suicide. We wished to determine whether these changes were more widespread and independent of psychiatric diagnoses.MethodsMu receptor levels were determined using [3 H]DAMGO binding in BA24 from 51 control subjects; 38 people with schizophrenia (12 suicides); 20 people with major depressive disorder (15 suicides); 13 people with bipolar disorder (5 suicides) and 9 people who had no history of psychiatric disorders but who died as a result of suicide. Mu receptor levels were further determined in BA9 and caudate-putamen from 38 people with schizophrenia and 20 control subjects using [3 H]DAMGO binding and, in all three regions, using Western blots. Data was analysed using one-way ANOVAs with Bonferroni’s Multiple Comparison Test or, where data either didn’t approximate to a binomial distribution or the sample size was too small to determine distribution, a Kruskal-Wallis test with Dunn’s Multiple Comparison Test.Results[3 H]DAMGO binding density was lower in people who had died as a result of suicide (p<0.01). People with schizophrenia who had died as a result of suicide had lower binding than control subjects (p<0.001), whilst people with bipolar disorder (non- suicide) had higher levels of binding (p<0.05). [3 H]DAMGO binding densities, but not mu protein levels, were significantly decreased in BA9 from people with schizophrenia who died as a result of suicide (p<0.01).ConclusionsOverall these data suggest that mu opioid receptor availability is decreased in the brains of people with schizophrenia who died as a result of suicide, which would be consistent with increased levels of endogenous ligands occupying these receptors.

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Section: Discussionsupporting

confidence: 56%

Mu opioid receptor availability in people with psychiatric disorders who died by suicide: a case control study

et al. 2012

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“…On the basis of the hypothesis that opioidergic mechanisms are involved in the pathophysiology and symptoms of schizophrenia (Volavka et al, 1979;Schmauss and Emrich, 1985;Nemeroff and Bissette, 1988), opioid antagonists were evaluated for potential antipsychotic efficacy in numerous clinical trials (McNicholas and Martin, 1984;Nemeroff and Bissette, 1988;Welch and Thompson, 1994). On the whole, they were safe and well tolerated and resulted in significant improvements of various aspects of schizophrenic symtomatology such as positive and deficit symptoms, polydipsia, alcoholism, and tardive dyskinesia in some (Watson et al, 1978;Lehmann et al, 1979;Berger et al, 1981;Nishikawa et al, 1994a, b;Marchesi et al, 1995;Petrakis et al, 2004;Wonodi et al, 2004), but not all (Volavka et al, 1977;Pickar et al, 1982) participants.…”

Section: Opioid Antagonists May Improve Hedonic Deficits In Patients mentioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

133

142

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Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

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“…In addition, opioid μ receptors modulate mesolimbic-mesocortical dopamine activity [ 7 ]. It has been suggested that some symptoms might be precipitated by alterations in BE level associated with a dysfunction in the modulatory effect of endogenous opioids on the dopaminergic system [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma β-Endorphin Concentration and Antipsychotic Treatment Outcome in Schizophrenia: 1-Year Follow-Up

et al. 2020

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Opiate antagonists for the treatment of schizophrenia

Cited by 12 publications

References 36 publications

Mu opioid receptor availability in people with psychiatric disorders who died by suicide: a case control study

Mu opioid receptor availability in people with psychiatric disorders who died by suicide: a case control study

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Plasma β-Endorphin Concentration and Antipsychotic Treatment Outcome in Schizophrenia: 1-Year Follow-Up

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