beta-endorphin and Schizophrenia

In the 10 years since Hughes et al (1975) identified from porcine brain two related pentapeptides with potent opiate activity, abnormalities of endorphin and enkephalin production or metabolism have been postulated in many disease states. The possibility of an advance in our understanding of the aetiology of functional psychiatric illness has led to a considerable body of research, which is discussed in this paper.

Topics: Animals; beta-Endorphin; Depression; Endorphins; Humans; Schizophrenia

Topics: beta-Endorphin; Bipolar Disorder; Brain; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Endorphins; Humans; Injections, Intravenous; Injections, Spinal; Renal Dialysis; Schizophrenia

Topics: Adult; Antipsychotic Agents; Apomorphine; beta-Endorphin; Drug Tolerance; Endocrine System Diseases; Endorphins; Female; Genetic Variation; Homovanillic Acid; Humans; Hydrocortisone; Hypothalamus; Luteinizing Hormone; Male; Methoxyhydroxyphenylglycol; Middle Aged; Nervous System Diseases; Norepinephrine; Prolactin; Receptors, Adrenergic, alpha; Receptors, Dopamine; Schizophrenia; Thyrotropin

Topics: beta-Endorphin; Depression; Dopamine; Endorphins; Hemoperfusion; Humans; Psychopathology; Schizophrenia; Schizophrenia, Paranoid; Time Factors; Toxemia

Topics: Affective Disorders, Psychotic; Animals; beta-Endorphin; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Endorphins; Growth Hormone; Humans; Hydrocortisone; Methylphenidate; Models, Psychological; Naloxone; Prolactin; Schizophrenia

Topics: Adult; beta-Endorphin; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Electroencephalography; Endorphins; Humans; Injections, Intravenous; Injections, Spinal; Male; Middle Aged; Prolactin; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia

Topics: Affective Disorders, Psychotic; Animals; Anxiety; beta-Endorphin; Catatonia; Dyskinesia, Drug-Induced; Electroconvulsive Therapy; Endorphins; Humans; Mental Disorders; Narcotic Antagonists; Opioid-Related Disorders; Pain; Rats; Receptors, Opioid; Renal Dialysis; Schizophrenia; Stress, Psychological

Topics: Animals; beta-Endorphin; Blood-Brain Barrier; Brain; Endorphins; Enkephalins; Humans; Nociceptors; Peptides; Rats; Schizophrenia; Stress, Physiological; Synaptic Transmission

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

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.

Topics: Adult; beta-Endorphin; Double-Blind Method; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

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.

Topics: Adrenocorticotropic Hormone; Adult; Arousal; beta-Endorphin; Blood Glucose; Clinical Trials as Topic; Deoxyglucose; Depressive Disorder; Double-Blind Method; Epinephrine; Female; Fluphenazine; Grief; Homovanillic Acid; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Mental Disorders; Methoxyhydroxyphenylglycol; Mood Disorders; Norepinephrine; Pituitary-Adrenal System; Schizophrenia; Stress, Psychological

The biological enigma of schizophrenia has led, on the basis of thin evidence, to widen the field of clinical research to a study of endomorphines in this disease. Too many different methods of measuring the levels of opiate peptides in the CSF have been used so that it is not possible to analyse the results statistically. Clinical trials of agonists and antagonists to the opiate receptors have once again emphasised the biochemical heterogeneity of schizophrenics but have not allowed any confirmation that the endorphinical system plays any part in the genesis or symptomatology of schizophrenia. The presence of sub-groups who respond positively to experimental treatment can lead to the hope, despite the uncertainties of their mode of pharmacological action, to the next advance in the routine treatment of schizophrenia.

Topics: beta-Endorphin; Clinical Trials as Topic; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Humans; Naloxone; Peptide Fragments; Receptors, Opioid; Schizophrenia

Topics: beta-Endorphin; Bipolar Disorder; Brain; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Endorphins; Humans; Injections, Intravenous; Injections, Spinal; Renal Dialysis; Schizophrenia

The neuropeptides desenkephalin-gamma-endorphin (DE gamma E) and ceruletide were administered intramuscularly to patients with schizophrenic psychoses following a double-blind placebo-controlled design, including a total of 44 subjects. Neuroleptic medication was continued during the experimental period, which was started with one placebo injection for all patients. One week later subjects received a single intramuscular injection with 3 mg DE gamma E, 40 micrograms ceruletide or placebo. After an interval of 10 days, the patients received six similar injections over a period of 2 weeks. Treatment with either peptides resulted in a decrease of psychotic symptomatology as compared to placebo treatment. The beneficial effect of the peptides lasted at least 2 weeks after the experimental treatment period. Of the 14 patients treated with placebo only, three showed a slight response. Of the 30 patients treated with the neuropeptides, eight did not respond (DE gamma E: 3; ceruletide: 5), eight had a slight response (DE gamma E: 6; ceruletide: 2) and 14 responded moderately or markedly (DE gamma E: 6; ceruletide: 8). No obvious difference between the effects of the two neuropeptides was found, besides a somewhat earlier onset of the effect of ceruletide. Patients presenting relatively less negative psychotic symptoms were particularly susceptible to treatment with either peptide. Apart from slight and short-lasting gastrointestinal complaints after the first injections with ceruletide in some patients, no side effects were observed.

Topics: Adult; beta-Endorphin; Ceruletide; Clinical Trials as Topic; Double-Blind Method; Endorphins; Gastrointestinal Diseases; Humans; Injections, Intramuscular; Schizophrenia

Topics: Affective Disorders, Psychotic; Animals; beta-Endorphin; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Endorphins; Growth Hormone; Humans; Hydrocortisone; Methylphenidate; Models, Psychological; Naloxone; Prolactin; Schizophrenia

Topics: Adult; beta-Endorphin; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Electroencephalography; Endorphins; Humans; Injections, Intravenous; Injections, Spinal; Male; Middle Aged; Prolactin; Psychiatric Status Rating Scales; Psychotic Disorders; 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

The response of plasma beta-endorphin (ir) to infusions of randomly assigned d-amphetamine (20 mg) and placebo was studied in eight schizophrenic patients. Although there was no statistically significant difference between the response to d-amphetamine and placebo, significant increases in plasma beta-endorphin (ir) levels were observed following each infusion. Although heterogeneity in beta-endorphin (ir) response was observed, individual differences did not relate to clinical variables such as abnormalities on computed tomography or "process-reactive" distinctions. An excessive beta-endorphin response to placebo in schizophrenia is discussed.

Topics: Adult; beta-Endorphin; Dextroamphetamine; Endorphins; Female; Growth Hormone; Humans; Male; Prolactin; Psychotic Disorders; Schizophrenia

Topics: beta-Endorphin; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Endorphins; Humans; Schizophrenia

Topics: beta-Endorphin; Clinical Trials as Topic; Electroencephalography; Endorphins; Humans; Naloxone; Prolactin; Schizophrenia

Topics: Adult; beta-Endorphin; Clinical Trials as Topic; Double-Blind Method; Endorphins; Female; Humans; Male; Schizophrenia

The subjects were 13 psychiatric inpatients with tardive dyskinesia. Each subject participated in two sessions. Either naloxone (10 mg) or placebo was administered intravenously during each session. In a subset of subjects (n = 7), blood samples for beta-endorphin were drawn before and at 30 and 60 minutes after the injection. The Abnormal Involuntary Movement Scale was administered before and at 10, 20, 40, 60, 120, and 360 minutes after the injection. Double-blind procedures were maintained throughout the experiment. Neither naloxone nor placebo had any appreciable effect on the involuntary movements. Naloxone elicited a significant increase in the plasma beta-endorphin.

Topics: Adult; Affective Disorders, Psychotic; Aged; beta-Endorphin; Dyskinesia, Drug-Induced; Endorphins; Female; Humans; Male; Middle Aged; Naloxone; Psychotic Disorders; Receptors, Dopamine; Schizophrenia

Animal experiments have shown that the gamma-endorphin fragment des-enkephalin-gamma-endorphin (DE gamma E; beta-lipotropin 66-77) is the shortest sequence with neuroleptic-like activity with potency comparable to des-tyrosine-gamma-endorphin. We postulated that DE gamma E may be an endogenous peptide implicated in psychopathologic disease, particularly schizophrenia. To investigate the purported antipsychotic action of DE gamma E, 23 patients with different types of relapsing schizophrenia were treated with DE gamma E dissolved in saline or placebo. Neuroleptic medication was continued during the experimental period. In the first single-blind trial, two patients were treated with 1 mg of DE gamma E and two with 10 mg of DE gamma E intramuscularly (IM) daily for ten days. In the second double-blind placebo-controlled trial 13 patients were treated with 3 mg of DE gamma E IM daily for ten days and six received placebo. Of the 17 patients treated with DE gamma E, two did not respond, 11 had a slight to moderate effect, and four responded markedly. No side effects were observed. The response to DE gamma E appeared to be negatively correlated with the dosage of neuroleptic medication and the duration of the last psychotic episode. These results support the hypothesis that disturbances in gamma-endorphin fragmentation might contribute to the pathogenesis of schizophrenic psychoses.

Topics: Adult; beta-Endorphin; Delusions; Double-Blind Method; Endorphins; Female; Hallucinations; Humans; Male; Middle Aged; Schizophrenia; Schizophrenic Psychology; Thinking

Topics: beta-Endorphin; Clinical Trials as Topic; Double-Blind Method; Endorphins; Humans; Male; Middle Aged; Naloxone; Random Allocation; Receptors, Opioid; Schizophrenia; Schizophrenic Psychology

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Bipolar Disorder; Clinical Trials as Topic; Depression; Dose-Response Relationship, Drug; Double-Blind Method; Endorphins; Half-Life; Humans; Kinetics; Prolactin; Psychiatric Status Rating Scales; Schizophrenia

We aimed to compare neuropeptide levels between patients with major psychiatric disorders and healthy controls and examine their association with symptoms and cognitive function.. The participants were 149 patients with schizophrenia, 115 patients with bipolar disorder (BD), 186 unremitted patients with major depressive disorder (MDD), and 350 healthy controls. Psychiatric (schizophrenic, manic, and depressive) symptoms, sleep state, and cognitive (premorbid intelligence quotient, general cognitive, and memory) functions were evaluated. A multiplex immunoassay kit was used to measure cerebrospinal fluid (CSF) and plasma α-melanocyte-stimulating hormone (MSH), β-endorphin, neurotensin, oxytocin, and substance P levels.. The verification assay revealed that CSF α-MSH, β-endorphin, neurotensin, oxytocin, and substance P levels were too low to be reliably measured, while plasma α-MSH, β-endorphin, neurotensin, oxytocin, and substance P levels could be successfully measured. Plasma α-MSH, β-endorphin, neurotensin, oxytocin, and substance P levels were not significantly different between patients with schizophrenia, BD, or MDD and healthy controls. Plasma α-MSH, β-endorphin, neurotensin, oxytocin, and substance P levels were not significantly correlated with psychiatric symptom scores in patients with schizophrenia, BD, or MDD and cognitive function scores in patients or healthy controls.. Our data suggest that plasma neuropeptide levels do not elucidate the involvement of neuropeptides in the pathology of schizophrenia, BD, or MDD.

Topics: alpha-MSH; beta-Endorphin; Bipolar Disorder; Depressive Disorder, Major; Humans; Immunoassay; Neurotensin; Oxytocin; Schizophrenia; Substance P

BACKGROUND Increased levels of endogenous opioids have been observed in patients with schizophrenia; however, the influence of these endogenous opioids on the biology of schizophrenia remains unclear. The aim of this study was to evaluate the impact of beta-endorphin (BE) on the course of schizophrenia and risk of relapse. MATERIAL AND METHODS The study included 25 patients hospitalized with schizophrenia and 47 controls. Their symptoms were evaluated using Positive and Negative Syndrome Scale (PANSS) and composite index at five points: at the onset of hospitalization; after 4, 6 and 10 weeks of treatment; and after 12 months. ß-endorphin plasma concentrations were assessed in patients at study enrollment and after 6 weeks of treatment. Data regarding rehospitalization during follow-up were also collected. RESULTS Patients had higher BE concentration than controls at study enrollment (P=0.002) and after 6 weeks (P=0.000). BE levels increased during treatment (mean 0.538ng/mL vs. mean 0.624 ng/mL; P=0.007). No correlation was found between BE concentration and PANSS subscale score at any stage of the study. A higher BE level at study enrollment was related to a predominance of negative symptoms after 1 year, measured with composite index (R=-0.404; P=0.045). Patients who were later hospitalized again were significantly more likely to demonstrate an increase in BE levels over 6 weeks (P=0.001). CONCLUSIONS Individuals with schizophrenia demonstrated higher BE concentrations than healthy controls; this tendency was particularly apparent in those affected by negative symptoms. The imbalance in the endogenous opioid system might adversely alter the course of disease and predispose patients to persistence of negative symptoms, despite antipsychotic treatment.

Topics: Adult; Antipsychotic Agents; beta-Endorphin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence; Schizophrenia; Treatment Outcome

The odor identification ability and its hedonic judgment in patients with schizophrenia were evaluated in the study. The association between olfactory performance and negative symptoms and β-endorphin concentration was also analyzed.. Study groups consisted of 23 patients with negative symptoms (PN) and 25 without predominant negative symptoms (PP) and 21 healthy individuals. The University of Pennsylvania Smell Identification Test, odor hedonic evaluation, and plasma concentrations of β-endorphin assay in all participants were performed.. PN perceived the poorer olfactory identification; nevertheless, they evaluated unpleasant odors as more pleasant than PP and controls. Beta-endorphin concentration was significantly higher among PN than in other study groups. No association was observed between β-endorphin and odors identification and odor hedonic judgment among all study groups.. There is potential relationship between increased β-endorphin concentration and severity of negative symptoms. Patients with predominant negative symptoms tend to evaluate odors as significantly more pleasant. Individuals with this subtype of schizophrenia might present specific, altered pattern of smell identification and hedonic judgment. Presumably, β-endorphin has no direct influence on olfactory identification performance and hedonic judgment in schizophrenia.

Topics: Adult; beta-Endorphin; Female; Humans; Judgment; Male; Middle Aged; Odorants; Olfaction Disorders; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Young Adult

Recent studies associate cathepsin K with schizophrenia. The endogenous substrates of this protease, however, remain to be identified. We show here that cathepsin K is capable of liberating met-enkephalin from beta-endorphin (beta-EP) in vitro. To verify if this process might possibly contribute in the pathogenesis of schizophrenia post mortem brains of patients suffering from this disease were analysed immunohistochemically for the presence and co-localization of cathepsin K and beta-EP. In support of a functional role of the observed formation of met-enkephalin on the expense of beta-EP increased numbers of cathepsin K immunoreactive cells, but diminished numbers of both beta-EP-positive cells and double-positive (cathepsin K/beta-EP) cells were found in left and right arcuate nucleus of schizophrenics. In addition a reduced density of beta-EP-immunoreactive neuropil (fibres, nerve terminals) was estimated in the left and right paraventricular nucleus (PVN) of individuals with schizophrenia. Our results imply that cathepsin K, which becomes up-regulated in its cerebral expression by neuroleptic treatment, might significantly contribute to altered opioid levels in brains of schizophrenics, which have previously been reported by us and others, and might reinforce the interest in the putative roles of endorphin and enkephalins in neuropsychiatric disorders.

Topics: Adult; Antipsychotic Agents; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Brain Chemistry; Cathepsin K; Cathepsins; Cell Line, Tumor; Enkephalin, Methionine; Female; Haloperidol; Humans; Immunohistochemistry; Male; Middle Aged; Neurons; Paraventricular Hypothalamic Nucleus; RNA, Messenger; Schizophrenia; Spectrometry, Mass, Electrospray Ionization

In order to elucidate whether the hypothalamic expression of beta-endorphin is altered in patients with mental disorders we studied the cellular localization of the peptide in arcuate nucleus neurons as well as the beta-endorphinergic innervation of paraventricular neurons in nine schizophrenics, six subjects with depression, and nine controls. A polyclonal antiserum against beta-endorphin was employed for the immunohistochemical detection of the peptide in sections of postmortem human brains. Quantitative analysis revealed that the number of beta-endorphin-containing arcuate neurons was statistically reduced in schizophrenics and depressives in comparison to controls. Moreover, the number of endorphinoceptive (i.e. beta-endorphin-innervated) paraventricular nerve cells was also lower in psychiatric patients than in control cases. Our results showing an altered endorphinergic system in human hypothalami of schizophrenics and depressives might contribute to a renewal of interest in this peptide as a possible factor of importance in psychiatric disorders.

Topics: Adult; Aged; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Cerebral Ventricles; Depressive Disorder; Female; Functional Laterality; Humans; Immunohistochemistry; Male; Middle Aged; Nerve Fibers; Neurons; Paraventricular Hypothalamic Nucleus; Reference Values; Schizophrenia

Cholecystokinin (CCK), beta-endorphin (BE), and vasoactive intestinal peptide (VIP) in peripheral blood mononuclear cells from 30 drug-naive schizophrenics compared to 22 healthy controls were studied. Patients were evaluated with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of the Negative Symptoms (SANS) at baseline (TO), and after four weeks (T4) in nine patients who were subsequently treated with haloperidol (HL). Neuropeptide concentrations in peripheral blood mononuclear cells (PBMC) were measured at TO and, for the treated patients, at T4. There was a negative correlation between CCK and SANS baseline scores and a trend for patients who responded poorly to HL (i.e. patients with a prevalence of negative symptomatology) to have lower CCK basal values.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Behavioral Symptoms; beta-Endorphin; Case-Control Studies; Chi-Square Distribution; Cholecystokinin; Female; Haloperidol; Humans; Leukocytes, Mononuclear; Male; Neuropeptides; Regression Analysis; Schizophrenia; Severity of Illness Index; Treatment Outcome; Vasoactive Intestinal Peptide

Neuropeptides, initially thought to be common features of gut and brain, are only synthesized in immune cells and modulate immune functions. The presence and possible functions of these peptides in immune cells in both physiological or pathological conditions have been investigated in our laboratory in the last years. Some of the data obtained are reviewed here, and future developments of the field are indicated.

Topics: Adult; Aged; Aged, 80 and over; Aging; Animals; beta-Endorphin; Brain; Chemotaxis; Cholecystokinin; Digestive System; Headache; Humans; Lymphocytes; Male; Middle Aged; Neuropeptides; Rats; Rats, Sprague-Dawley; Schizophrenia; Vasoactive Intestinal Peptide

We have previously shown that a number of depressed patients demonstrated a failure to suppress corticotrophic secretion, as measured by beta-Endorphin/beta-Lipotropin (beta-End/beta-LPH levels), following dexamethasone challenge. The current study is an extension and replication of these findings, as well as an analysis of some of the biological variables which may contribute to the variance in beta-End/beta-LPH nonsuppression. We continue to observe a high rate of beta-End/beta-LPH nonsuppression in depressed patients following dexamethasone; this escape at the pituitary level is even observed in a number of patients who demonstrate normal cortisol suppression. Advancing age, particularly in women, led to higher baseline cortisol, lower baseline beta-End/beta-LPH, and a greater likelihood of being a nonsuppressor on one or both measures.

Topics: Adrenocorticotropic Hormone; Adult; Age Factors; Aged; beta-Endorphin; beta-Lipotropin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Psychiatric Status Rating Scales; Schizophrenia; Seasonal Affective Disorder; Sex Factors

Beta-endorphin, cholecystokinin and vasoactive intestinal peptide were measured in peripheral blood mononuclear cells of healthy controls, and schizophrenic patients at the first diagnosis before any treatment and after 2 or 15 d of treatment with haloperidol. Beta-endorphin concentrations were similar in controls and untreated patients, and increased with treatment. Cholecystokinin concentrations were higher in patients than in controls, and decreased during treatment. Vasoactive intestinal peptide was lower in patients and did not change with treatment. These observations are consistent with measurements of the same peptides in autopsy samples or cerebrospinal fluid. Peripheral blood mononuclear cells might be an useful tool for the study of some neuropeptides in brain.

Topics: Adolescent; Adult; beta-Endorphin; Cholecystokinin; Female; Haloperidol; Humans; Male; Monocytes; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Vasoactive Intestinal Peptide

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

Topics: Adolescent; Adult; Autistic Disorder; beta-Endorphin; Child; Female; Humans; Male; Radioimmunoassay; Schizophrenia

The effects of short- and long-term neuroleptic therapy on peripheral secretion of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) were examined in 25 chronic schizophrenic patients. Haloperidol was given to 8 patients for 10 days (group A: 0.1 mg/kg b.w./day) and to another group of 8 patients for 30 days (group B: 10-18 mg/day). The other 9 patients were given a combination of haloperidol (6-30 mg/day) with either chlorpromazine (25-75 mg/day), clotiapine (40-60 mg/day), or fluphenazine decanoate (25-75 mg/month) for 14-18 months (group C). beta-EP and beta-LPH levels were assayed before and after each treatment. Haloperidol plasma levels were assayed in group B patients at the end of treatment. beta-EP mean basal levels were higher in patients than in controls; however, beta-LPH mean basal levels were higher only for group A patients. After treatment, the mean levels did not differ from those prior to therapy in groups A and B, while beta-LPH levels were significantly higher in group C. Level increases or decreases in single patients did not correlate with drug dose or duration of treatment, with baseline peptide levels or with the clinical effects of the various treatments.

Topics: Adult; Antipsychotic Agents; beta-Endorphin; beta-Lipotropin; Chlorpromazine; Chronic Disease; Dibenzothiazepines; Drug Therapy, Combination; Female; Fluphenazine; Haloperidol; Humans; Male; Middle Aged; Receptors, Opioid; Schizophrenia

Topics: Adult; beta-Endorphin; beta-Lipotropin; Bipolar Disorder; Chronic Disease; Circadian Rhythm; Depressive Disorder; Dexamethasone; Endorphins; Female; Humans; Insulin; Male; Middle Aged; Schizophrenia

The following data were obtained from 36 male chronic schizophrenics (ICD 295.6) of 47 +/- 11 years of age, treated with neuroleptics for the last 16 +/- 6 years: Age, age at first manifestation of disease, duration and dosage scheme of neuroleptic therapy and number of electroconvulsive shock treatments. Blood samples were drawn both under neuroleptic treatment and after a 12-day withdrawal of neuroleptics, for determining cortisol, prolactin, beta-endorphin and noradrenaline. Psychopathology was assessed by standard criteria via BPRS. In 27 patients CT determination was carried out to determine the breadth of the third ventricle and the ventricular brain ratio. Withdrawal of neuroleptics resulted in a marked improvement, whereas 11 patients showed pronounced deterioration of their psychotic symptoms. In respect of the entire group there was a significant improvement of anergy, while disturbances of thinking were significantly enhanced. Serum levels of beta-endorphin and cortisol increased after neuroleptic withdrawal, whereas the levels of prolactin and of noradrenaline dropped. A considerable proportion of the patients showed a distinct extension of the ventricular system, but the CT variables correlated only slight with psychopathological parameters or their changes after neuroleptic withdrawal. The other variables, too, were without clinically relevant prognostic importance compared with the psychopathological changes after neuroleptic withdrawal. These variables were e.g. demography, psychopathology, therapy and neuroendocrinology.

Topics: Adult; Antipsychotic Agents; beta-Endorphin; Cerebral Ventricles; Chronic Disease; Electroconvulsive Therapy; Endorphins; Hormones; Humans; Hydrocortisone; Male; Norepinephrine; Prolactin; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome; Tomography, X-Ray Computed

The diurnal variation of plasma beta endorphin was studied in ten schizophrenics, and in age/sex matched control subjects. In the controls beta endorphin was high in the morning (21.0 +/- 3.5 pmol/l) and decreased towards evening. In the schizophrenic group the beta endorphin fluctuated randomly, ranging within 9-40 pmol/l throughout the day. Plasma cortisol showed a normal diurnal pattern in both groups. The mean plasma cortisol levels in the schizophrenics were significantly higher than in the controls throughout the day. The pattern of plasma human growth hormone (hGH) level was similar in both groups at the time tested. It is hypothesized that the instability of beta endorphin secretion may contribute to the pathogenesis of schizophrenia.

Topics: Adult; beta-Endorphin; Blood-Brain Barrier; Circadian Rhythm; Endorphins; Female; Growth Hormone; Humans; Hydrocortisone; Male; Schizophrenia

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.

Topics: beta-Endorphin; Brain; Chromatography, High Pressure Liquid; Endorphins; Humans; In Vitro Techniques; Schizophrenia; Tissue Distribution

Topics: Adrenocorticotropic Hormone; Adult; Affective Disorders, Psychotic; beta-Endorphin; beta-Lipotropin; Endorphins; Female; Humans; Male; Middle Aged; Pituitary Gland; Pro-Opiomelanocortin; Schizophrenia

Severity of tardive dyskinesia (TD) and psychopathology of 36 chronic schizophrenic patients under long-term treatment with neuroleptics (NL) was rated during NL therapy and again 12 days after NL withdrawal. Both times serum levels of prolactin, norepinephrine, beta-endorphin, and cortisol were determined. In 27 of these patients ventricular-brain ratio, width of third ventricle, maximal width of anterior horns, distance between choroid plexus, and width of four largest sulci were also measured. Fifteen patients had no signs of TD; 14 had moderate, and 7 severe TD. TD was not related to age, age at onset of illness, duration of illness, dosage and type of neuroleptics, number of ECTs, or any endocrine variable. Psychopathology was barely related to TD, but after NL withdrawal, patients with TD tended to show more deterioration, particularly with regard to thought disorder and activation. With regard to computer-tomographic (CT) variables, patients without TD showed significantly less sulcal enlargement than those with TD. These results indicate that individual predisposition, which may have led to the development of TD, also seems to involve a higher risk of relapse after NL withdrawal.

Topics: Adult; Antipsychotic Agents; beta-Endorphin; Brain; Dyskinesia, Drug-Induced; Endorphins; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Norepinephrine; Prolactin; Psychiatric Status Rating Scales; Schizophrenia; Substance Withdrawal Syndrome; Tomography, X-Ray Computed

The psychopathology of 36 chronic, schizophrenic patients who had been on maintenance neuroleptics was rated during neuroleptic therapy and after 12 days of neuroleptic withdrawal. At both times, hormonal serum levels were also determined. Moreover, in 27 of these patients, ventricle-brain ratio, maximal width of the third ventricle, and sulcal widening were measured on computed tomography (CT). Neuroleptic withdrawal resulted in individually different psychopathological changes: 7 patients improved, 11 worsened. Within the whole group, thought disorder deteriorated, and anergia improved. Levels of cortisol and beta-endorphin increased; those of prolactin and norepinephrine decreased. The majority of patients showed ventricular enlargement, which was marginally related to reduced thought disorder. CT and endocrine variables were slightly related to psychopathology or psychopathological effects of neuroleptic withdrawal.

Topics: Adult; Antipsychotic Agents; beta-Endorphin; Cerebral Ventricles; Chronic Disease; Endorphins; Humans; Hydrocortisone; Male; Middle Aged; Norepinephrine; Prolactin; Schizophrenia; Schizophrenic Psychology

Topics: beta-Endorphin; Bipolar Disorder; Depressive Disorder; Endorphins; Female; Humans; Male; Psychotic Disorders; Radioligand Assay; Receptors, Opioid; Schizophrenia

Baseline plasma levels of beta-endorphin, beta-lipotropin, and ACTH were assayed in 37 patients with chronic schizophrenia: 24 men and 13 women, 28 with hebephrenic and nine with paranoid schizophrenia. None of the patients had received any medication for at least 10 days. The mean values of both opioids were significantly higher in the schizophrenic patients than in 21 age- and sex-matched control subjects. Insulin stimulation and dexamethasone suppression tests were given to eight of the patients, and the circadian rhythms of beta-endorphin, beta-lipotropin, ACTH, and cortisol were assayed in the same eight patients. Insulin stimulation, dexamethasone suppression test results, or circadian rhythmicity was impaired in seven of these eight patients.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Chronic Disease; Circadian Rhythm; Dexamethasone; Endorphins; Female; Humans; Insulin; Male; Middle Aged; Schizophrenia; Schizophrenia, Disorganized; Schizophrenia, Paranoid

In 14 schizophrenic patients, treated with neuroleptic drugs, and in 7 patients, treated with high-dosage diazepam, beta-endorphin-like immunoreactivity in plasma has been measured by use of a highly sensitive and relatively specific radioimmunoassay. Neuroleptic treatment induced a significant increase of beta-endorphin-like immunoreactivity (beta-ELI). The pharmacological and clinical implications of this finding are discussed. High-dosage diazepam treatment induces a slight reduction of plasma beta-ELI, a finding which is attributed to antistress effect of diazepam.

Topics: Adolescent; Adult; Antipsychotic Agents; beta-Endorphin; Diazepam; Dose-Response Relationship, Drug; Endorphins; Female; Fluspirilene; Haloperidol; Humans; Male; Schizophrenia; Thioridazine

In the past decade both basic and clinical research on endogenous opiates has involved many aspects of medicine. This review focuses on the clinical literature that relates physiology and pathophysiology of the endogenous opiates to schizophrenia. Three major investigative approaches are described and their results evaluated. These approaches are described and their results evaluated. These approaches include assays of endogenous opiates in the context of clinical illness and use of exogenous opiates as well as exogenous opiate antagonists in the treatment of clinical illness. Current understanding at both the basic science and clinical research levels does not allow firm conclusions about the role of endogenous opiates in schizophrenia; however, the evolution of the growing understanding is used by the author to provide a speculative hypothesis.

Topics: Animals; Antipsychotic Agents; beta-Endorphin; Double-Blind Method; Drug Therapy, Combination; Endorphins; Humans; Peptide Fragments; Rats; Schizophrenia; Schizophrenic Psychology

In 23 acute, unmedicated, schizophrenic patients, psychotic behaviour and beta-endorphin serum level were measured before and during four weeks of neuroleptic therapy. Prior to drug treatment, beta-endorphin level of all patients was within the normal range. Neuroleptic therapy induced marked elevations of beta-endorphin in eight subjects; statistical analysis revealed a slight but significant increase for the whole group. This endocrine effect was not correlated with therapeutic efficacy of neuroleptic treatment.

Topics: Adult; Antipsychotic Agents; beta-Endorphin; Endorphins; Female; Haloperidol; Humans; Male; Penfluridol; Perazine; Schizophrenia

Due to asymmetry of brain neurotransmitters and differential hemispheric information processing modes, it is suggested that the excessive use of one information processing mode could engender a state of brain reactivity whose neurochemical correlates would be either a rise in melatonin or beta-endorphin in systemic circulation. Since melatonin and beta-endorphin have opposite effects on lung-mediated regulation of prostaglandins, it is further suggested that the pulmonary inactivation of prostaglandin E1 would either be increased or inhibited. Low levels of PGE1 would engender high levels of PGE2 whose effects would explain the findings in schizophrenics of: 'reducing' pattern of visual evoked response, cerebral atrophy, and viral and autoimmune phenomena. The primacy of the disordered cognitive style in leading up to the immunological, biochemical and neuropathological processes is stressed. Implications of this model for understanding depression, anxiety and phobic disorders, autism, attention deficit disorder, obesity, alcoholism, smoking, drug addiction, sexual deviations, and certain psychosomatic and psychophysiological disorders are suggested.

Topics: Alprostadil; beta-Endorphin; Brain; Cognition; Depression; Endorphins; Humans; Lung; Melatonin; Models, Psychological; Neurotransmitter Agents; Prostaglandins E; Schizophrenia

Topics: Adult; beta-Endorphin; Double-Blind Method; Endorphins; Humans; Hydrocortisone; Male; Naloxone; Prolactin; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Topics: beta-Endorphin; Brain; Chromatography, High Pressure Liquid; Endorphins; Female; Humans; In Vitro Techniques; Male; Membranes; Schizophrenia; Time Factors

In a double-blind sham replacement study, eight drug-free schizophrenic patients underwent 10 active and 10 sham hemodialysis for 20 weeks. At the end of the 10 active dialyses, none of the patients appeared to be improved in psychotic, affective, or social symptoms. Active dialysis was associated with a "startle" response in heart rate and skin conductance to auditory stimuli, while sham dialysis was associated with an "orienting" response. Night-recorded sleep electroencephalography was unaffected by active dialysis. Spinal fluid beta-endorphin-like immunoreactivity levels were unchanged after active treatment. The behavioral improvements reported in other studies may be related to "stress," psychotherapeutic support, spontaneous remissions, neuroleptic withdrawal, denial of symptoms, or diagnostic differences. This study did not confirm the claims for hemodialysis as a specific therapeutic intervention in schizophrenia.

Topics: Adult; Behavior; beta-Endorphin; Double-Blind Method; Electroencephalography; Endorphins; Female; Galvanic Skin Response; Heart Rate; Humans; Male; Pilot Projects; Psychiatric Status Rating Scales; Renal Dialysis; Schizophrenia; Sleep

Topics: beta-Endorphin; Depressive Disorder; Double-Blind Method; Endorphins; Humans; Hydrocortisone; Naloxone; Prolactin; Psychotic Disorders; Psychotropic Drugs; Receptors, Opioid; Schizophrenia

Topics: Adult; Aged; Antipsychotic Agents; beta-Endorphin; Endorphins; Humans; Hydrocortisone; Male; Middle Aged; Prolactin; Schizophrenia; Schizophrenic Psychology

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

beta-Endorphin immunoreactivity was measured in cerebrospinal fluid of 75 medication-free subjects: normal, depressed, schizophrenic, and anorexic. No significant differences in beta-endorphin immunoreactivity were found. Affinity extraction chromatography revealed beta-lipotropin and beta-endorphin, but no apparent precursors.

Topics: Adolescent; Adult; Affective Disorders, Psychotic; Aged; Anorexia Nervosa; beta-Endorphin; Bipolar Disorder; Depressive Disorder; Endorphins; Female; Humans; Male; Middle Aged; Reference Values; Schizophrenia

Topics: beta-Endorphin; Dyskinesia, Drug-Induced; Endorphins; Female; Humans; Middle Aged; Renal Dialysis; Schizophrenia

Topics: Adult; Age Factors; beta-Endorphin; Depressive Disorder; Endorphins; Female; Humans; Male; Psychiatric Status Rating Scales; Radioimmunoassay; Schizophrenia; Sex Factors

In this paper we have reported the results of studies in psychiatric patient groups using the strategy of measuring opioid activity and beta-endorphin (ir) in CSF. Our findings do not lend support to the notion of excess endorphin activity in schizophrenia, but rather suggest the possibility of a decrease in endogenous opioid activity in some schizophrenic patients. In affectively ill patients our data suggest that there may be a relative change in endogenous opioid system activity across state change in manic-depressive illness. Who also found a relationship between nurses' ratings of anxiety and CSF opioid activity in depressed patients, although it is unknown whether this directly relates to the pathophysiology of this symptom, or is related to stress response. The relationship between CSF opioid activity and HPA axis activity, as reflected by urinary free cortisol excretion, supports the notion of important physiologic relationships between these systems and raises the issue of a role for the endogenous opioid system in the abnormal activation of this system in depression. Finally, the finding of increased CSF opioid activity in anorexia nervosa patients when a minimum weight coupled with data relating endogenous opioids to eating behavior raises interesting questions regarding a possible involvement of the endogenous opioid system involvement in this illness.

Topics: Adult; Anorexia Nervosa; beta-Endorphin; Bipolar Disorder; Depressive Disorder; Endorphins; Female; Humans; Male; Psychotic Disorders; 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

The authors measured total opioid activity by radioreceptor assay in the CSF of 41 normal subjects and 89 unmedicated psychiatric patients, including schizophrenic, schizoaffective, depressed, and manic diagnostic groups. Schizophrenic men had significantly lower levels of opioid activity than the normal men, although these levels did not significantly differ from levels of other male patients. The authors observed higher opioid activity during mania than during depression in paired samples for 4 manic-depressive patients. beta-Endorphin immunoreactivity in a subsample of the same subjects was no different in the patient group than in the normal group, suggesting that the differences in CSF opioid activity between schizophrenic men and normal patients may be related to opioids other than beta-endorphin.

Topics: Adult; beta-Endorphin; Bipolar Disorder; Depressive Disorder; Endorphins; Female; Humans; Male; Mental Disorders; Psychotic Disorders; Radioligand Assay; Receptors, Opioid; Schizophrenia

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Chronic Disease; Endorphins; Female; Haloperidol; Humans; Male; Middle Aged; Mood Disorders; Schizophrenia

Topics: beta-Endorphin; Endorphins; Humans; Renal Dialysis; Schizophrenia

beta-endorphin concentration in cerebrospinal fluid (CSF) in 21 schizophrenic and 15 neurological patients was determined by radioimmune assay. On the basis of the obtained data a correlation between the change of beta-endorphin level in CSF of schizophrenics and that of the clinical state of these patients was assumed as a result of a short-term discontinuance of the treatment. It was established that the reduction of beta-endorphin level in CSF of schizophrenics correlates with the intensification of hallucinatory-delusional disorders.

Topics: Adult; Antipsychotic Agents; beta-Endorphin; Endorphins; Humans; Male; Middle Aged; Radioimmunoassay; Schizophrenia; Schizophrenia, Paranoid

Topics: beta-Endorphin; Endorphins; Humans; Schizophrenia