Increased CSF levels of endorphines in chronic psychosis

Terenius, Lars; Wahlström, Agneta; Lindström, Leif; Widerlöv, Erik

doi:10.1016/0304-3940(76)90086-0

Cited by 281 publications

(49 citation statements)

References 12 publications

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“…Robust elevations of endogenous opiates concentrations in the cerebral spinal fluid and in plasma (Terenius et al, 1976;Lindstrom et al, 1978Lindstrom et al, , 1986Rimon et al, 1980;Brambilla et al, 1984;Marchesi et al, 1995) is a relatively consistent clinical finding in schizophrenia. Opiates levels tend to parallel the severity of psychosis (Terenius et al, 1976;Lindstrom et al, 1978;Rimon et al, 1980;Marchesi et al, 1995), suggesting involvement of this neurochemical effect in schizophrenia neuropathology (Volavka et al, 1979;Schmauss and Emrich, 1985;Nemeroff and Bissette, 1988).…”

Section: Abnormal Opioidergic Function May Impair Liking Processes Inmentioning

confidence: 97%

“…Opiates levels tend to parallel the severity of psychosis (Terenius et al, 1976;Lindstrom et al, 1978;Rimon et al, 1980;Marchesi et al, 1995), suggesting involvement of this neurochemical effect in schizophrenia neuropathology (Volavka et al, 1979;Schmauss and Emrich, 1985;Nemeroff and Bissette, 1988).…”

Section: Abnormal Opioidergic Function May Impair Liking Processes Inmentioning

confidence: 99%

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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

138

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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Section: Abnormal Opioidergic Function May Impair Liking Processes Inmentioning

confidence: 97%

Section: Abnormal Opioidergic Function May Impair Liking Processes Inmentioning

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

138

142

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“…In addition, most of these effects are reversible by naloxone. These preliminary results suggested to some that-the endorphins could be an etiological factor in mental illness (3,8), but the nature and specification of this action remains to be determined.Opiate receptors and enkephalin-like peptides have been found in the region of the ventral tegmental area (VTA) (9), and in at least some accounts receptors appear to be localized on mesolimbic dopamine neurons (9, 10). These mesolimbic dopamine neurons are thought to be involved in the locomotor stimulation produced by psychomotor stimulants (11, 12) but also may have a role in general activation and the actual organization of behavior (13,14).…”

mentioning

confidence: 86%

mentioning

confidence: 99%

Locomotor activation induced by infusion of endorphins into the ventral tegmental area: evidence for opiate-dopamine interactions.

Stinus¹,

Koob²,

Ling³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

144

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,-Endorphin in nanomole quantities produced a stimulation of locomotor activity when infused into the region of the dopamine cell bodies of the ventral tegmental area (VTA) in rats. a-, -y-, and des-Tyr-y-endorphin produced similar effects, but the D-alanine analogues of a-and y-endorphin produced a larger and longer-lasting activation, presumably reflecting their resistance to degradation. This locomotor activation was reversible by pretreatment with naloxone and b destruction of the terminal projections of the mesocorticolimzic dopamine system originating in the VTA. These results demonstrate that locally infused endorphin can interact with the opioid receptors in the VTA, and they suggest a means by which endorphins activate limbic excitability. The identification and localization within the central nervous system of endogenous peptides with opiate-like actions suggested that these substances may act as central neurotransmitters (1, 2). Both [Metlenkephalin [/3-lipotropin-(61-65)] and f3-endorphin (3-END) [/3-lipotropin-(61-91)] exhibit opiate-like activity when injected into the ventricles (3, 4). These effects have included analgesia, catatonia, loss of corneal and tail pinch reflexes, and wet-dog shakes (3), and :3-END appeared to be more potent than [Met]enkephalin (5-7). In addition, most of these effects are reversible by naloxone. These preliminary results suggested to some that-the endorphins could be an etiological factor in mental illness (3,8), but the nature and specification of this action remains to be determined.Opiate receptors and enkephalin-like peptides have been found in the region of the ventral tegmental area (VTA) (9), and in at least some accounts receptors appear to be localized on mesolimbic dopamine neurons (9, 10). These mesolimbic dopamine neurons are thought to be involved in the locomotor stimulation produced by psychomotor stimulants (11, 12) but also may have a role in general activation and the actual organization of behavior (13,14). In fact, some authors have suggested that the activation of the mesolimbic dopamine system may be an important model of schizophrenia (15). This intriguing similarity of the putative function for the mesolimbic dopamine system and the endogenous opiate systems requires further analysis of their interaction at the behavioral level, and our initial studies have concentrated on the activation of the mesolimbic dopamine system as measured by simple locomotor activity.Recent work has demonstrated that morphine and [D-Ala2, Met]enkephalin when injected into the VTA can produce significant increases in locomotor activity that may reflect an activation of these mesolimbic dopamine neurons (16,17). The purpose of the present study was to determine whether 1-END also interacts with the opiate receptors in the VTA to produceThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 2323 locomot...

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“…Terenius ef al. (21) found increased levels of non-beta-endorphin fractions in the cere-patients. Following medication, these increased levels returned to normal.…”

Section: Introductionmentioning

confidence: 97%