Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptides derived from pro-opiomelanocortin (POMC) influence neurodevelopmental processes. Earlier studies indicated that MSH/ACTH compounds improved behavioral efficiency in retarded individuals. Recent studies have shown that opiate blockers reduce treatment-resistant self-injurious behavior (SIB), an autistic-like, developmental disorder. Although the exact mechanisms are unknown, prenatal POMC disregulation, addiction to endogenous opiates and elevated pain threshold have been proposed to account for this behavior. In study one, four SIB patients were given 0, 25, 50 or 100 mg of naltrexone on separate weeks in a double blind, Latin square design. A specific dose dependent reduction in SIB was observed in three patients. In study two, plasma b-endorphin was measured in 40 patients with SIB, a related behavior, stereotypy (ST) or controls. SIB and ST patients had higher levels of endorphin than controls. These data added new support for the role of b-endorphin in a treatment-resistant patient group.
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PMID:Beta-endorphin disregulation in autistic and self-injurious behavior: a neurodevelopmental hypothesis. 246 89

A subgroup of patients with personality disorders from the DSM-III-R (American Psychiatric Association 1987) "flamboyant" cluster is characterized by repetitive self-injurious behavior (SIB) apparently not motivated by suicidal intent. After describing the clinical and demographic characteristics of these patients, the clinical and preclinical evidence suggesting the involvement of endogenous opiate systems in this behavior is reviewed. Patients with personality disorders and SIB have been found to have elevated levels of plasma beta-endorphin. However, the available evidence is not sufficient to show whether this is a cause of or a consequence of SIB. Behavioral stereotypies resulting in self-injury in animals and SIB in mentally retarded patients have been shown to be abolished by opiate antagonist administration in a significant proportion of both groups. The available evidence suggests that clinical trials of oral opiate antagonist drugs should be undertaken because of the promise such drugs have in the treatment of this sometimes life-threatening disorder.
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PMID:Rationale for clinical trials of opiate antagonists in treating patients with personality disorders and self-injurious behavior. 269 84

Groups of clients exhibiting both self-injurious behavior (SIB) and stereotypy, stereotypy alone, SIB alone, or neither of these types of behavior were rated in terms of response to sedative-hypnotic medication. Sixty-eight percent of the clients with both SIB and stereotypy maintained wakefulness and were either resistive, combative, restless, uncooperative, or abusive after treatment with sedative-hypnotics. Thirty-nine percent of the clients with only SIB and 35 percent of the clients with only stereotypy evidenced such "paradoxical" responses to these medications. None of the matched control clients displayed paradoxical responses. This result suggests that an impaired endogenous opiate system characterized by increased levels of beta-endorphin may mediate and maintain a type of syndrome of SIB that involves the presence of stereotypy, implying the need for a new diagnostic classification and treatment of these aberrant behavioral disorders.
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PMID:Relationship of sedative-hypnotic response to self-injurious behavior and stereotypy by mentally retarded clients. 663 79

We measured CSF levels of beta-endorphin, an opioid hormone, in 19 patients with infantile autism and in 3 patients with Rett syndrome, and compared them with control values. In infantile autism, CSF levels of beta-endorphin did not differ significantly from those of age-matched controls. There was no significant correlation between CSF levels and clinical symptoms, including self-injurious behavior, pain insensitivity, and stereotyped movement. However, CSF levels of beta-endorphin were significantly higher in the patients with Rett syndrome than in the control (p < .05). Data suggest that neurons containing beta-endorphin may not be involved in patients with infantile autism. Thus, there is no relationship between dysfunction of brain opioid and autism.
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PMID:CSF beta-endorphin levels in patients with infantile autism. 910 66

Self-injurious behavior (SIB) and stereotyped behavior (SB) are major challenges for professionals in the field of mental retardation. From animal experiments it has become obvious that these behavioral disturbances are not purposeless but may emerge secondary to restrictive environment and may serve de-arousing objectives. In mentally retarded subjects, several hypotheses have been formulated concerning the pathogenesis of SIB, particularly about the involvement of serotonin and beta-endorphin, which are supported by beneficial treatment effects of the opiate antagonist naltrexone and serotonin modulating compounds, respectively. The present study was designed to investigate basal levels of stress-hormonal and serotonergic parameters as well as plasma levels of amino-acids and the beta-carboline norharman in a group of 64 mentally retarded subjects with SB and/or SIB. Allocation to three different groups comprising 17 retarded controls, 26 subjects with mainly SIB and 21 subjects with mainly SB, was originally performed using the scores on the factors Irritability, Stereotypic Behaviour and Hyperactivity of the Aberrant Behavioral Checklist. Because of the overlapping nature of the behavioral parameters, subjects were subsequently divided into three maximally contrasting groups, viz. predominantly SIB, predominantly SB and retarded controls, each comprising 11 subjects. With respect to beta-endorphin, no differences were found either between both the original and maximally contrasting groups or in comparison to nonretarded controls. As compared to retarded controls, a tendency to lower values for total cortisol and cortisol binding globulin appeared to be present in the SIB group, whereas in the SB group a tendency toward higher levels of the major serotonin metabolite 5-HIAA was found. In the contrasting SB group, a trend toward decreased total cortisol level was observed as compared to the retarded control group. In addition, significantly lower values for norharman and tryptophan were demonstrated in the total group of mentally retarded subjects as compared to non-retarded controls. The results of the present study, yielding co-existent disturbances in stress-hormonal and monoaminergic mechanisms as well as in the metabolism of norharman, are in line with the hypothesis that mentally retarded subjects are at risk for the development of stress-related behavioral disorders such as SIB and SB.
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PMID:Stress and self-injurious behavior; hormonal and serotonergic parameters in mentally retarded subjects. 1007 Nov 78

Proopiomelanocortin (POMC) contains several interesting, behaviorally active peptides. Release patterns of these fragments have been related to bizarre episodes of self-injurious behavior (SIB) among autistic individuals. Moreover, elevation in beta-endorphin (betaE) but not ACTH levels was associated with a positive response to an acutely administered, centrally acting opioid blocker among autistic individuals exhibiting SIB. In the present study, POMC fragments were measured in 12 self-injurious patients before and after long term (3 month) treatment with an opiate blocker naltrexone (NTX). POMC fragments were sampled from blood collected at the beginning of the baseline and placebo-controlled treatment phases of the study. Results indicated that the co-release (coupling) of POMC fragments were stable over time and the profile of POMC fragments in plasma predicted the effectiveness of a CNS acting drug in autistic subjects who self-injure.
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PMID:Uncoupling of proopiomelanocortin (POMC) fragments is related to self-injury. 1095 98

Self-injurious behavior (SIB) is an untreatable and often life-threatening problem among individuals with developmental disorders, especially those diagnosed with autism. Functioning, relationships and processing of the proopiomelanocortin (POMC) system are "uncoupled" in subgroups of self-injuring individuals resulting in different ratios of ACTH and opioids in the bloodstream, particularly under conditions of stress. In this study, relations between SIB and POMC were evaluated in a multi-year study of the largest prospective sample studied to date. Observations were collected on palmtop computers for 45 treatment-resistant patients who exhibited chronic SIB. Behavior of each subject was observed in natural settings without disruption or intrusion, for continuous, 2.5-h periods, two times a day (morning and afternoon), 4 days a week for two consecutive weeks, for a total of 40 h/subject. Blood was collected in the morning, late afternoon and immediately after an SIB episode on two separate occasions separated by at least 6 months. Levels of beta-endorphin (beta E) and ACTH were assayed by RIA. We discovered that the SIB was the best predictor of subsequent SIB. Moreover, the majority of subjects exhibited this contagious pattern of SIB. Levels of POMC fragments were reliable over a 6- to 9-month period. Subjects exhibiting POMC disregulation characterized by high morning levels of beta E had the highest transitional probabilities of SIB (i.e. contagious patterns; F=8.17, P<0.01). These findings suggest that subjects with "contagious" SIB may represent a behavioral phenotype associated with disregulated expression of the POMC gene.
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PMID:Disregulation of proopiomelanocortin and contagious maladaptive behavior. 1222 Jul 43

Frequent or severe abnormal behavior may be associated with the release of endorphins that positively reinforce the behavior with an opiate euphoria or analgesia. One line of research exploring this association involves the superhormone, proopiomelanocortin (POMC). The products of POMC appear to be dysregulated in some human subjects who exhibit self-injurious behavior (SIB). Macaque monkeys have POMC very similar to humans, and some laboratory macaques display SIB or frequent stereotypies. We investigated associations between plasma levels of three immunoreactive POMC fragments with possible opioid action and abnormal behavior ratings in macaques. In 58 adult male and female macaques (24 Macaca fascicularis and 34 Macaca nemestrina), plasma levels of intact beta-endorphin (betaE) and the N-terminal fragment (BEN) were significantly higher in animals with higher levels of abnormal behavior. The C-terminal fragment (BEC) was significantly higher in males but unrelated to ratings of abnormal behavior. Levels of ACTH, cortisol, and (betaE-ACTH)/betaE dysregulation index were unrelated to abnormal behavior. None of the POMC products differed significantly by subjects' species, age, or weight. The finding that intact beta-endorphin is positively related to abnormal behavior in two species of macaque is consistent with some previous research on human subjects and nonprimates. The positive relation of the N-terminal fragment of betaE to abnormal behavior is a new finding.
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PMID:Beta-endorphin levels in longtailed and pigtailed macaques vary by abnormal behavior rating and sex. 1771 39

While the origins and developmental course of self-injurious behavior (SIB) remain relatively unknown, recent studies suggest a biological imbalance may potentiate or provoke the contagious recurrence of SIB patterns in individuals with severe developmental disabilities (DD). Evidence from several laboratories indicates that functioning, relations, and processing of a stress-related molecule, proopiomelanocortin (POMC) may be perturbed among certain subgroups of individuals exhibiting SIB. The current investigation employed a unique time-pattern analysis program (THEME) to examine whether recurrent temporal patterns (T-patterns) of SIB were related to morning levels of two POMC-derived hormones: beta-endorphin (betaE) and adrenocorticotropic hormone (ACTH). THEME was used to quantify highly significant (non-random) T-patterns that included SIB within a dataset of in situ observational recordings spanning 8 days ( approximately 40 h) in 25 subjects with DD. Pearson's product-moment analyses revealed highly significant correlations between the percentage of T-patterns containing SIB and basal levels of both betaE and ACTH, which were not found with any other "control" T-patterns. These findings support the hypothesis that the recurrent temporal patterning of SIB represents a unique behavioral phenotype directly related to perturbed levels of POMC-derived stress hormones in certain individuals with severe DD.
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PMID:Temporal patterns of self-injurious behavior correlate with stress hormone levels in the developmentally disabled. 1791 41

Tryptophan hydroxylase-2 (TPH2) synthesizes neuronal serotonin and is linked to numerous behavioral traits. We have previously characterized the functionality of polymorphisms (especially 2051A>C) in 3'-untranslated region (3'-UTR) of rhesus monkey TPH2 (rhTPH2). This study further assessed the functionality of additional polymorphisms (-1605T>C, -1491Tn, -1485(AT)n, -1454A>G, -1325In>Del and -363T>G) in rhTPH2 5'-flanking region (5'-FR), and evaluated the effects of rhTPH2 5' and 3' genotypes on central serotonin turnover, hypothalamic-pituitary-adrenal (HPA) axis function and self-injurious behavior (SIB) in 32 unrelated adult male monkeys of Indian origin. Haplotypes of the rhTPH2 5'-FR polymorphisms exert a significant, cell-dependent effect on reporter gene expression, primarily conferred by -1485(AT)n. The -1485(AT)n and 2051A>C polymorphisms interact to influence cerebrospinal fluid (CSF) 5-HIAA and plasma adrenocorticotropic hormone (ACTH) in the afternoon. While -1485(AT)n exerts significant main effects on the afternoon cortisol level and nocturnal HPA negative feedback, 2051A>C has significant main effects on the morning cortisol level and cortisol response to ACTH challenge, as well as marginally significant main effects on the daytime HPA negative feedback and self-biting rate. In addition, the genotype/allele frequency of the 5'-FR -1325Ins>Del differed significantly between the self-wounders and non-wounders, whereas 3'-UTR 2128S>L polymorphism differed significantly in genotype/allele frequency between the high- and low-frequency biters. This study shows the functionality of rhTPH2 5'-FR polymorphisms, and provides evidence for the differential association of rhTPH2 5'-FR and 3'-UTR polymorphisms with HPA axis function and SIB. Our findings shed light on the role of TPH2 gene variance in physiology and behavioral traits, and also contribute to the understanding of the pathophysiology and genetics of SIB.
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PMID:TPH2 5'- and 3'-regulatory polymorphisms are differentially associated with HPA axis function and self-injurious behavior in rhesus monkeys. 2005 54


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