Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ninety-three patients with an exacerbation of chronic schizophrenia were included in a 4 week trial comparing placebo with 1, 3 and 10 mg des-enkephalin-gamma-endorphin (DE gamma E; beta-lipotrophin 66-77; Org 5878) per day (i.m.). Maintenance antipsychotic and other medications were continued unchanged. Treatment effects were assessed by means of the Comprehensive Psychopathological Rating Scale--subscale schizophrenia (CPRS-S), Brief Psychiatric Rating Scale (BPRS) and Global Assessment Scale (GAS) rating scales at weekly intervals. Safety data, i.e. laboratory investigations, vital signs and ECG recordings, were assessed before and during the trial. Side-effects were evaluated by means of a Record of Symptoms Emerging. Sixty-eight patients completed the trial, the reason for drop-out mainly being inadequate treatment effects and refusal of medication administration. One patient violated the protocol. After 4 weeks of treatment the mean CPRS-S score of the group receiving 10 mg DE gamma E daily had decreased statistically significantly more than the corresponding score of the placebo group (p less than 0.01). The same trend was apparent with BPRS (p = 0.08) and GAS (p greater than 0.1) scores. Therefore, the study should be considered inconclusive. No clinically relevant side-effects attributable to DE gamma E were observed.
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PMID:Des-enkephalin-gamma-endorphin in the treatment of schizophrenia. 223 65

The possibility has been mentioned that a change in the structure is responsible for the deviant behavioral activity of gamma-endorphin in extracts of postmortem brain and pituitary gland samples of schizophrenic patients. This paper describes the investigation of this possibility by means of: amino acid composition analysis of alpha- and gamma-endorphin isolated from a pituitary gland of a schizophrenic patient; and nucleotide sequence analysis of the gamma-endorphin coding region of pro-opiomelanocortin (POMC) mRNA from two other pituitary glands, using the primer extension method. Both methods require no more than a single pituitary to obtain reliable results. alpha- and gamma-endorphin were isolated from an acid extract by gel filtration and two subsequent HPLC steps. In addition, the gamma-endorphin region of beta-endorphin was analyzed by enzymatic cleavage of beta-endorphin and isolation of the resulting fragment. Single-stranded gamma-endorphin cDNA was synthesized by reverse transcriptase using total cellular pituitary RNA and a 5' 32P-labeled oligodeoxyribonucleotide primer (20-mer) hybridizing close to the gamma-endorphin coding region of POMC mRNA. Single-stranded cDNA was digested with restriction enzyme HaeIII which generated a 148 nucleotides long radioactive cDNA fragment containing the gamma-endorphin cDNA sequence. The sequence of the 148 nucleotides fragment was determined. Neither the amino acid composition analysis nor the amino acid sequence derived from the cDNA nucleotide sequence revealed differences between schizophrenics and controls. Thus, no evidence was found for changes in the amino acid sequence of pituitary gamma-endorphin in these analyses, which include 3 cases of schizophrenia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:gamma-Endorphin and schizophrenia: amino acid composition of gamma-endorphin and nucleotide sequence of gamma-endorphin cDNA from pituitary glands of schizophrenic patients. 242 70

Recently much interest has been shown in the antipsychotic efficacy of neuroleptic-like neuropeptides in schizophrenia. In this article the clinical effects of the non-opioid fragments of gamma-endorphin, the so-called gamma-type endorphins DT gamma E and DE gamma E are reviewed. In addition, preliminary clinical studies of peptides related to cholecystokinin are considered. It is concluded that gamma-type endorphins possess antipsychotic properties in a subgroup of patients who may belong to Type I schizophrenia. With cholecystokinin-related peptides, in particular ceruletide, antipsychotic effects have been reported, which seem to be more or less comparable to those observed with gamma-type endorphins.
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PMID:[Antipsychotic efficacy of neuroleptic neuropeptides in schizophrenia. Review of clinical data]. 245 39

A yin-yang hypothesis is presented linking noradrenergic activity, thromboxane, melatonin, left hemisphere functioning, and cyclic AMP on the one hand, and dopamine, beta-endorphin, calcium, right hemisphere functioning, and cyclic GMP on the other. It is further suggested that there is a yoking of NA, TXA2, serotonin and melatonin in the left hemisphere, and a similar yoking of DA, BE, calcium and cGMP in the right. Evidence is presented to support the hypothesis that each element (NA, TXA2, etc.) on one side can modulate or balance a corresponding element (DA, BE, etc.) on the other. It is suggested that thromboxane is the key element in noradrenergic overactivity and that not taking this into consideration has confounded much prior research. This theory takes into account information processing models as well as pharmacological data and neurochemical theory on coupling of adenylate cyclase to its hormone receptors. Inhibiting noradrenergic overactivity can be obtained by inhibiting thromboxane and concomitantly activating opiate receptors. This protocol may have clinical utility in treating a wide range of disorders such as: anxiety, depression, schizophrenia, sleeplessness, withdrawal states, enuresis, Gilles de la Tourette syndrome, Parkinsonism, Alzheimers, dementia, anorexia, infant ruminations, essential tremor, spasticity of spinal cord injury, diarrhoea, ulcerative colitis, extrapyramidal symptoms, akathisia, neuroleptic malignant syndrome, attention deficit disorder, hyperhidrosis, and possibly AIDS.
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PMID:Inhibiting noradrenergic overactivity by inhibition of thromboxane and concomitant activation of opiate receptors via dietary means. 254 22

This article presents a series of experiments that involves the development of three novel strategies for human stress research and the utilization of these strategies to examine neurobehavioral processes of stress in healthy volunteers, schizophrenia, and affective illness. The first strategy involved intravenous 2-deoxy-D-glucose (2DG) administration, a glucoprivic stressor. We found that glucoprivic stress results in dissociation of hypothalamus-pituitary-adrenal (HPA), adrenomedullary, and sympathoneural activity. In addition, glucoprivic stress in neuroleptic-treated schizophrenic patients caused heightened dopamine activity, as reflected by increased plasma homovanillic acid (HVA) levels and decreased adaptive responses as assessed by decreased food consumption following 2DG administration. These data suggest that neuroleptics do not prevent stress-related increases in dopamine activity and that schizophrenia may be associated with abnormalities in the stress response. The second strategy assessed effects of uncontrollable and identical amounts of controllable stress in volunteers and depressed patients. In volunteers, it was found that uncontrollable in comparison to controllable stress results in specific behavioral and neuroendocrine alterations. Moreover, uncontrollable stress exposure in depressed patients in comparison to volunteers produced greater alterations in behavioral ratings and plasma cortisol levels and that the uncontrollable stress related increases in helplessness ratings and cortisol levels were significantly correlated. These data suggest that depressed patients may have increased sensitivity to uncontrollable stress and that there may be an important interrelationship between the cognitive deficits of depression and the heightened HPA axis activity observed in these patients. Lastly, we used a naturalistic strategy to examine mechanisms relating childhood parental loss and the development of adult affective illness and found that among subjects with early parental loss histories, those who developed adult psychiatric illness had increased resting plasma levels of cortisol and beta-endorphin (ir) as compared with subjects with early loss and no adult history of psychiatric illness. Moreover, increased HPA activity in adulthood was significantly related to poor childhood adjustment to parental loss. The implications of the results of these studies are discussed.
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PMID:A.E. Bennett award paper. Experimental approaches to human stress research: assessment of neurobiological mechanisms of stress in volunteers and psychiatric patients. 255 97

Low levels of cerebrospinal fluid (CSF) somatostatin and abnormal response to dexamethasone are two neuroendocrine disturbances reported to appear in depression and other neuropsychiatric disorders. We measured the levels of CSF somatostatin in patients with schizophrenia (n = 44) and depression (n = 19). In view of in vitro and animal evidence of the ability of somatostatin to inhibit stimulated corticotropin secretion, we also administered the dexamethasone suppression test to a subgroup of the patients with schizophrenia (n = 16) and the total depressed group. Lower levels of CSF somatostatin were found in dexamethasone nonsuppressors regardless of diagnosis and were negatively correlated with maximum postdexamethasone cortisol level in the total and depressed patient groups. These data suggest a functional relationship between hypothalamic-pituitary-adrenal axis hyperactivity and reduced CSF somatostatin level.
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PMID:CSF somatostatin and abnormal response to dexamethasone administration in schizophrenic and depressed patients. 286 43

Clinical prospects of an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin (DT gamma E) in schizophrenia were examined by using the Brief Psychiatric Rating Scale (BPRS) and the electroencephalogram (EEG). Twelve inpatients with chronic schizophrenia were administered fixed doses of neuroleptics throughout the study. Six patients were treated with DN-1417 (DN-1417 group), and the remaining 6 patients with DT gamma E (DY gamma E group). One mg/day of DN-1417 or DT gamma E was given intramuscularly for 2 consecutive weeks followed by 1 week of no drug treatment. In the DN-1417 group, both total BPRS scores and scores on hallucinatory behaviour and unusual thought content decreased in the first and third weeks. The power values of alpha and beta activities from the frontal area increased in the first and third weeks, whereas an increase in alpha activity and a decrease of high-fast beta activity from the occipital area were obtained during the study. On the other hand, the DT gamma E group failed to show either a decrease in BPRS scores or any remarkable EEG changes except for a slight decrease in beta activity. These results suggest that the positive symptoms of schizophrenia are improved by DN-1417 treatment, and that the alterations in BPRS scores coincide with changes in the frontal EEG.
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PMID:A treatment trial with an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin in schizophrenia. 288 64

Incubation of beta-endorphin (beta-E; 25 microM) with twice-washed brain membrane homogenates leads to the formation of several biologically active peptide fragments which have been shown to be present in the brain. Based on clinical studies, some of these endorphin fragments have been shown to be active in patients with neuropsychiatric disease states. We studied the regional specificity of beta-E metabolism in frontal cortex versus putamen from sex and age matched controls versus subjects with a diagnosis of schizophrenia. The present study demonstrates that cortical tissue has a lower rate of gamma-endorphin production from beta-E and a similar rate of des-tyrosine-gamma-endorphin production. Significant differences were noted in the production of other active fragments (beta-E (1-16, 2-16, 6-21)). These results support the hypothesis that there is a regional specificity of beta-E metabolism in the brain, and these differences may have important functional consequences to secreted peptides and important clinical consequences in schizophrenia.
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PMID:Specific regional differences of in vitro beta-endorphin metabolism in schizophrenics. 294 88

It is suggested that the antipsychotic efficacy of opioids in patients suffering from schizophrenia may result from an interaction of opioids with the dopaminergic system. The modulatory effect of opioids on dopaminergic functions has already been demonstrated in basic experiments: Anatomical and biochemical data reveal an interaction between opioid receptors and dopamine (DA) actions on dopaminergic nerve terminals, cell bodies, and afferent nerve endings. Endogenous enkephalin levels correlate well with the endogenous dopamine content in various brain areas. Systemic or iontophoretic administration of morphine alters the spontaneous activity of ventral tegmental dopaminergic neurons. Morphine and enkephalin effectively enhance pituitary prolactin release, whereas dopamine inhibits it. Opioid agonists effectively alter DA release, DA reuptake, and DA metabolism in the striatum and substantia nigra. In reverse, chronic neuroleptic treatment enhances the synthesis and release of pituitary beta-endorphin. Opioids affect contralateral rotation elicited by dopamine agonists in animals with unilateral lesions of the nigrostriatal pathway. Phencyclidine, a psychotropic drug that shares certain pharmacological characteristics with the putative sigma-opioid receptor ligand SKF 10,047, indirectly mimics the effects of dopamine agonists on prolactin release, release of acetylcholine, etc. It is suggested that an imbalance of opiate-DA interaction might be involved in the pathogenesis of schizophrenia. Consequently, clinical studies on the effects of opioids on psychotic symptoms should also examine opioid influence on dopaminergic functions in these patients.
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PMID:Dopamine and the action of opiates: a reevaluation of the dopamine hypothesis of schizophrenia. With special consideration of the role of endogenous opioids in the pathogenesis of schizophrenia. 299 42

The authors presented evidence for the effect of 6 analogues of ACTN4-10 on teaching of albino rats in a labyrinth with negative electrocutaneous reinforcement. Sixteen series of experiments on 192 rats demonstrated a positive effect of corticotropin fragments on memory processes. The activating ACTH fragment effect was shown in recording the background and bioelectrically induced rabbit brain activity in response to a photo-flash in 36 experiments on 18 animals. Three groups of 30 patients with alcohol withdrawal syndrome, posttraumatic craniocerebral effect and schizophrenia received injections of corticotropin as a therapeutic agent. A high efficacy of corticotropin in the treatment of the alcohol withdrawal syndrome and after effect of craniocerebral injury and a low efficacy and sometimes aggravation of symptoms in schizophrenia patients were shown.
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PMID:[Psychotropic properties of corticotropin and its analogs]. 300 19


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