gamma-endorphin and Schizophrenia

Topics: Animals; Antipsychotic Agents; Brain; Cholecystokinin; Endorphins; gamma-Endorphin; Humans; Neuropeptides; Rats; Schizophrenia

Topics: Animals; Brain; Disease Models, Animal; Dopamine; Endorphins; gamma-Endorphin; Humans; Schizophrenia

Topics: beta-Endorphin; Endorphins; gamma-Endorphin; Humans; Receptors, Opioid; Schizophrenia

The pharmacological actions of gamma-type endorphins show similarities to those of the neuroleptics. Two fragments of gamma-endorphin (beta-LPH 61-77) were therefore tested in patients with schizophrenic and schizo-affective psychoses who had shown an insufficient response to neuroleptics. The fragments were DT gamma E (beta-LPH 62-77) and DE gamma E (beta-LPH 66-77). Some of the patients studied responded favorably to this treatment. A number of criteria of differentiation between responders and nonresponders are discussed. The influence of DT gamma E on the central DA metabolism differs from that of the neuroleptics. It is therefore conceivable that gamma-type endorphins represent a different principle of action. The therapeutic efficacy of these compounds lends support to the hypothesis that disorders of central endorphin metabolism may play a role in the pathogenesis of psychoses of the schizophrenic type.

Topics: beta-Endorphin; Brain; Clinical Trials as Topic; Dopamine; Double-Blind Method; Endorphins; gamma-Endorphin; Humans; Peptide Fragments; Psychotic Disorders; Receptors, Dopamine; Schizophrenia; Schizophrenic Psychology

Topics: Adult; beta-Endorphin; Brain; Clinical Trials as Topic; Dopamine; Double-Blind Method; Endorphins; Female; gamma-Endorphin; Humans; Male; Middle Aged; Peptide Fragments; Schizophrenia

Topics: Brief Psychiatric Rating Scale; Double-Blind Method; Drug Evaluation; Endorphins; gamma-Endorphin; Humans; Peptide Fragments; Psychotic Disorders; Schizophrenia

Topics: Animals; Binding Sites; Brain; Endorphins; Feedback; gamma-Endorphin; Humans; In Vitro Techniques; Limbic System; Rats; Receptors, Opioid; Schizophrenia

The concentrations of alpha-, beta- and gamma-endorphin were determined by radioimmunoassay in HPLC fractionated extracts of post mortem hypothalamic tissue obtained from schizophrenic patients and controls. The hypothalamic concentration of alpha- and gamma-endorphin was significantly higher in patients than in controls (+72.9% and +50.5% respectively). No difference was found in the concentration of beta-endorphin, the putative precursor of alpha- and gamma-endorphins. These results suggest a deviant metabolism of beta-endorphin in the brain of schizophrenic patients. Whether this phenomenon is related to the psychopathology, or is a consequence of ante mortem farmacotherapy, remains to be established.

Topics: Adult; Aged; Aged, 80 and over; alpha-Endorphin; beta-Endorphin; Chromatography, High Pressure Liquid; Endorphins; Female; gamma-Endorphin; Humans; Hypothalamus; Male; Middle Aged; Radioimmunoassay; Schizophrenia

The clinical response of schizophrenic patients to treatment with gamma-type endorphins was found to be associated with certain HLA class I antigens (Bw22, B15, B13). Moreover, pretreatment of lymphocytes from healthy donors with des-Tyr1-gamma-endorphin (DT gamma E) inhibits the complement-dependent cytotoxicity between alloantisera and those HLA antigens, of which the frequency was increased among schizophrenic patients, who respond well to the gamma-endorphin therapy. Also for the opiate antagonist, naloxon interactions with HLA class I antigens could be demonstrated. Using the inhibition assay with DT gamma E it was possible to detect a subtype of HLA-A2, which, until now, was only defined by cytotoxic T lymphocytes and biochemistry. These data suggest an interaction between the HLA class I antigens and the receptor(s) for DT gamma E and naloxon, which may support the hypothesis that HLA class I antigens play a role in many recognition processes. Their role in immunological recognition would then be only a specialized form of a more general function.

Topics: Antigen-Antibody Reactions; Endorphins; gamma-Endorphin; HLA Antigens; HLA-A2 Antigen; Humans; Isoantibodies; Receptors, Opioid; Schizophrenia

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)

Topics: Amino Acids; Animals; Base Sequence; DNA, Circular; Endorphins; gamma-Endorphin; Humans; Pituitary Gland; Schizophrenia

The hypothesis implicating the gamma-type endorphins in schizophrenia was initially based on animal data showing commonalities between the behavioral effects of these peptides and neuroleptics. Clinical studies have shown that these peptides have an antipsychotic action in a number of patients suffering from schizophrenic psychosis. The patients responding to the peptides are characterized by features at least partly resembling those characterizing type I schizophrenia. This may be consistent with the animal data showing that gamma-type endorphins may directly or indirectly control certain dopaminergic systems present in the nucleus accumbens. Genetical differences may exist between patients susceptible to and not susceptible to gamma-type endorphins, as has been concluded from studies concerning antigens of the HLA system.

Topics: Antipsychotic Agents; Brain; Endorphins; gamma-Endorphin; Humans; Schizophrenia

Topics: Adult; Arthritis, Rheumatoid; Celiac Disease; Child; Chromosome Mapping; Endorphins; Epitopes; gamma-Endorphin; Histocompatibility Antigens Class II; HLA Antigens; HLA-DR3 Antigen; Humans; Leprosy; Penicillins; Schizophrenia; T-Lymphocytes

In order to investigate whether genetic factors are involved in the response of schizophrenic patients to treatment with gamma-type endorphins, we typed 32 Dutch schizophrenic patients for the HLA-A, -B, -C and -DR antigens. The total patient group showed an increase of HLA-Bw4 and HLA-Cw1. A subgroup of 20 paranoid patients showed an increase of HLA-Cw1 and a significant heterogeneity for the HLA-C locus. In 16 patients who responded moderately or markedly to treatment with gamma-type endorphins, an increase of HLA-B15/Cw3 and a decrease of HLA-B17 were found as compared to 16 patients with no or a slight response. Moreover, HLA-B15 was particularly increased in those patients who responded markedly and remained free of psychotic symptoms for a period of at least 6 months after treatment with gamma-type endorphins (RR = 24.6, Puncorr. = 0.0015). Our results suggest that genetic factors coded for within the HLA region are associated with paranoid schizophrenia, and that HLA-B15/Cw3 is associated with a marked and prolonged response to treatment with gamma-type endorphins.

Topics: beta-Endorphin; Endorphins; gamma-Endorphin; HLA Antigens; HLA-B Antigens; HLA-B15 Antigen; HLA-C Antigens; Humans; Peptide Fragments; Schizophrenia

Topics: Animals; Antipsychotic Agents; Behavior, Animal; beta-Endorphin; Dopamine; Double-Blind Method; Endorphins; gamma-Endorphin; Humans; Peptide Fragments; Psychiatric Status Rating Scales; Psychotic Disorders; Rats; Receptors, Dopamine; Receptors, Opioid; Schizophrenia; Schizophrenic Psychology