beta-endorphin and Depressive-Disorder

The purpose of this article is to review the literature on the effects of the menstrual cycle on dependent variables in mood disorder research to inform investigators which physiological measures are likely to be significantly affected by menstrual cycle fluctuations and precisely how they might be affected. The following variables are discussed: prolactin; growth hormone; the hypothalamic-pituitary-thyroid axis (including thyrotropin, triiodothyronine, and thyroxine); the hypothalamic-pituitary-adrenal axis (cortisol, corticotropin, and beta-endorphin); melatonin; sleep; body temperature; and neurotransmitter activity (serotonergic and adrenergic systems). Body temperature and plasma and urinary norepinephrine vary predictably over the menstrual cycle. Prolactin and beta-endorphin may have peaks in the periovulatory phase, whereas serotonin levels in platelet-poor plasma may reach a nadir at that time. Triiodothyronine, thyroxine, cortisol, and melatonin do not appear to vary systematically over the course of the menstrual cycle, whereas the data for growth hormone, thyrotropin, corticotropin, and sleep are inconclusive.

Topics: Adult; beta-Endorphin; Body Temperature; Circadian Rhythm; Depressive Disorder; Female; Growth Hormone; Humans; Hydrocortisone; Melatonin; Menstrual Cycle; Mood Disorders; Premenstrual Syndrome; Prolactin; Research Design; Seasons; Serotonin; Sleep; Thyroid Hormones

1. There are major changes in progesterone, oestrogen, cortisol and beta-endorphin level associated with parturition, and as all these can be psychoactive it is likely that they contribute to the mood changes that can occur at this time. However evidence for their involvement is, at present, indirect. 2. Postnatal depression itself appears to be a heterogeneous condition with different times of onset, and it is probable that various biological and social factors play a role to a differing degree in different individuals. 3. About half of postnatal depression appears to arise in the first two weeks after childbirth. Some cases follow a period of early euphoria. 4. A different subgroup is associated with thyroid dysfunction, which peaks two to five months postpartum. 5. The tyramine test does not predict vulnerability to postnatal depression. 6. It is suggested that in future research the time course of onset of the depression, and the nature of the mood changes that occur in the first postpartum week, are investigated as possibly relevant variables.

Topics: Affect; beta-Endorphin; Depressive Disorder; Estrogens; Female; Humans; Hydrocortisone; Progesterone; Puerperal Disorders; Time Factors

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: Adrenocorticotropic Hormone; beta-Endorphin; Brain; Corticotropin-Releasing Hormone; Depressive Disorder; Endorphins; Gonadotropins, Pituitary; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Neurotransmitter Agents; Physostigmine; Pituitary Gland; Pituitary-Adrenal System; Thyrotropin

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: Adult; Aged; beta-Endorphin; Chronic Disease; Depressive Disorder; Dexamethasone; Endorphins; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Pain; Pituitary Hormones, Anterior; Pituitary-Adrenal System

Excess secretion of cortisol in depressed patients has been documented by a number of investigators, which is presumed secondary to increased corticotropin (ACTH) and ACTH-releasing hormone (CRH) secretion. To unmask the proposed increased central (CRH) drive, we administered metyrapone in the AM to 13 depressed and 13 age- and sex-matched normal control subjects. Metyrapone administration resulted in a prompt decrease in plasma cortisol and in an increase in 11-deoxycortisol, the inactive precursor, in all subjects. Both depressed patients and normal control subjects demonstrated clear increases in ACTH and beta-lipotropin/beta-endorphin production. There were no significant differences between patients and controls in any hormonal measures following metyrapone administration. These data suggest that: 1) in the absence of negative feedback (cortisol blockade), mildly to moderately depressed outpatients do not manifest increased central drive in the morning; and 2) the secretory capacity of the corticotropes do not differ between such depressed patients and controls.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Circadian Rhythm; Corticotropin-Releasing Hormone; Depressive Disorder; Female; Hormones; Humans; Hydrocortisone; Male; Metyrapone; Pituitary Gland

Previous studies by a number have investigators have documented a decreased adrenocortotropic hormone (ACTH) and beta-lipotropin/beta-endorphin (beta-End) response to ovine corticotropin-releasing factor (oCRF) in depressed patients. Since depressed patients demonstrate higher plasma cortisol concentrations at the time of oCRF challenge, it is difficult to determine if the decreased ACTH response is due to enhanced negative feedback of cortisol on ACTH release or an alteration in CRF receptors in depressed patients. To evaluate the response to oCRF in an "open feedback loop" system, we administered metyrapone 750 mg at 4 PM and 7:30 PM, followed by administration of oCRF 0.3 microgram/kg at 8 PM in 10 normal controls and 10 depressed patients. Administration of metyrapone at this time in the circadian rhythm clamped plasma cortisol concentrations to less than 2 micrograms/dl but did not result in rebound ACTH or beta-End secretion in control subjects. In control subjects, metyrapone administration produced a 85% blockade of the cortisol response as well as a 3-fold greater beta-End response compared to administration of the same dose of oCRF without metyrapone. The 10 depressed patients and their matched controls demonstrated identical beta-End responses (integrated response for controls = 291 +/- 61, for patients = 352 +/- 86) and cortisol responses (integrated response for controls = 187 +/- 38, for patients = 206 +/- 52) to oCRF following metyrapone pretreatment. These data confirm that corticotroph CRF receptors are normal in depressed patients, and that cortisol feedback plays an essential role in the abnormal ACTH and beta-End response to oCRF in depressed patients.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Bipolar Disorder; Circadian Rhythm; Corticotropin-Releasing Hormone; Depressive Disorder; Feedback; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metyrapone; Personality Inventory; Pituitary-Adrenal System; Receptors, Corticotropin-Releasing Hormone; Reference Values

Day-time plasma beta-endorphin/beta-lipotrophic hormone (beta-ENDO/beta-LPH), ACTH and cortisol have been determined in 26 patients with major depression and 25 controls. beta-ENDO/beta-LPH and cortisol were significantly elevated in patients, while ACTH was not. Cortisol levels were significantly negatively correlated with age in controls as were beta-ENDO/beta-LPH and ACTH. In patients, by contrast, cortisol levels were positively, albeit not significantly, related to age. Peptide levels were not related to age in the patient group. Instead, beta-ENDO/beta-LPH was negatively correlated with clinical ratings of symptom severity in patients and positively associated with an acute psychosocial precipitant. The findings cast further light on beta-ENDO/beta-LPH as a measure of hypothalamic-pituitary over activity in depressive illness. A negative association with symptom severity suggests that beta-ENDO/beta-LPH responses are, like those of ACTH, down-regulated in the course of depressive illness.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; beta-Lipotropin; Depressive Disorder; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Personality Inventory; Pituitary-Adrenal System; Psychiatric Status Rating Scales

Graded doses arginine-vasopressin (AVP) were administered to depressed patients and control subjects to compare the sensitivity of the pituitary-adrenal system of these subjects for this compound. The plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin were measured before and after intravenous AVP injection. The hormonal output was taken as a measure of pituitary-adrenal function. In control subjects 3 doses AVP and placebo were used, whereas in patients two doses AVP, a low and a high dose, and placebo were tested. All tests were carried out in the afternoon when the pituitary-adrenal system is stable and more susceptible for stimulation. Patients were subdivided into dexamethasone suppressors and nonsuppressors based on their DST status before testing to look for differences among these groups. Control subjects showed no response of the hormones to the lowest dose AVP and a moderate response to the higher doses. Interestingly, depressed patients as compared to controls responded more to the lowest dose AVP in particular with respect to ACTH. DST status did not influence the results. These findings suggest an enhanced sensitivity of the pituitary to low doses AVP in depressed patients. Thus, AVP might play a role in HPA dysfunction in depression.

Topics: Adrenocorticotropic Hormone; Adult; Arginine Vasopressin; beta-Endorphin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Male; Pituitary-Adrenal System; Psychiatric Status Rating Scales; Radioimmunoassay; Stimulation, Chemical

The effects of phosphatidylserine (BC-PS) on cognitive, affective and behavioural symptoms were studied in a group of 10 elderly women with depressive disorders. Patients were treated with placebo for 15 days, followed by BC-PS (300 mg/day) for 30 days. The Hamilton Rating Scale for Depression, Gottfries-Bråne-Steen Rating Scale, Nurse's Observation Scale for Inpatient Evaluation and Buschke Selective Reminding Test were administered before and after placebo and after BC-PS therapy, to monitor changes in depression, memory and general behaviour. At the same time, basal plasma levels of noradrenaline, MHPG, DOPAC, HVA and 5-HIAA, and GH/beta-endorphin/beta-lipotropin responses to clonidine stimulation were measured. BC-PS induced consistent improvement of depressive symptoms, memory and behaviour. No changes in amine metabolite levels or in hormonal responses to alpha 2-adrenoceptor stimulation were observed.

Topics: 3,4-Dihydroxyphenylacetic Acid; Aged; Aged, 80 and over; Arousal; beta-Endorphin; beta-Lipotropin; Cerebral Cortex; Clinical Trials as Topic; Clonidine; Depressive Disorder; Female; Growth Hormone; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Methoxyhydroxyphenylglycol; Norepinephrine; Phosphatidylserines; Receptors, Adrenergic; Recurrence

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

To investigate the mechanism underlying disturbances in hypothalamopituitary-adrenal (HPA) function in depressed patients, the dexamethasone suppression test (DST) was compared with a cortisol suppression test (CST) and placebo treatment in depressed patients and control subjects. Plasma levels of cortisol, ACTH and beta-endorphin were assessed at 3 times during the day after treatment with a single dose of exogenous steroid. Both dexamethasone and cortisol treatment resulted in suppression of cortisol, ACTH and beta-endorphin in control subjects, while neither treatment had any effect on the hormone levels in those depressed patients who showed cortisol nonsuppression after dexamethasone. In the depressed patients who were cortisol suppressors after dexamethasone, cortisol treatment only slightly changed plasma levels of beta-endorphin, although they were suppressed after dexamethasone treatment. In addition, high levels of both cortisol and beta-endorphin were observed after placebo treatment in all depressed patients compared to control subjects, probably due to the absence of the normally occurring decrease of these hormones during the day in these patients. Cortisol treatment, but not dexamethasone treatment, discriminated depressed patients from controls with respect to their beta-endorphin plasma levels. However, it is not yet clear whether these different effects of the two steroids are related to a different mode of action of these steroids in depressed patients. beta-Endorphin seems to be a useful marker in detecting disturbances in HPA function among depressed patients.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged; Psychiatric Status Rating Scales

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

Sixty patients with chronic pain of the low back or cervical spine concomitant with clinical depression were studied in a 6-week, randomized, double-blind comparison of doxepin and placebo. Significant improvements in the doxepin-treated group compared to placebo or to baseline values were seen on Hamilton depression scores, Global Assessment Scale scores, pain severity, percent of time pain felt, and effect of pain on activity, sleep, and muscle tension. Some improvements were observed after 1 week of treatment; the most improvement occurred at 6 weeks, when the mean doxepin dosage was approximately 200 mg/day and plasma doxepin and nordoxepin averaged 80 ng/ml. No significant harmful effects were observed. Neither plasma beta-endorphin nor enkephalin-like activity demonstrated significant differences from baseline. These data indicate that doxepin is a valuable treatment for patients with chronic pain and depression.

Topics: beta-Endorphin; Chronic Disease; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Doxepin; Endorphins; Enkephalins; Female; Humans; Male; Middle Aged; Pain; Placebos; Psychiatric Status Rating Scales; Random Allocation; Time Factors

Doxepin and desipramine at final doses of 188 and 173 mg/day, respectively, were compared in 36 volunteers with major affective or dysthymic disorder and chronic back pain. Both drugs produced significant decreases in depression, with an overall response rate of 70%; no significant difference was seen between groups. Pain ratings also decreased significantly in both groups (overall response rate = 50%); pain severity showed a better response to doxepin than to desipramine. While baseline pain, depression, and anxiety were correlated, treatment changes in these measures did not correlate. CSF beta-endorphin levels did not change with treatment. The usefulness of an antidepressant with anxiolytic properties, such as doxepin, is discussed.

Topics: Adult; Anxiety Disorders; Back Pain; beta-Endorphin; Chronic Disease; Clinical Trials as Topic; Depressive Disorder; Desipramine; Doxepin; Endorphins; Female; Helplessness, Learned; Humans; Male; Personality Inventory; Placebos; Psychiatric Status Rating Scales

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 Authors report a double-blind study to compare mianserin and chlorimipramine efficacy in the treatment of two groups of 30 depressed patients. The trial confirms that mianserin has an antidepressant effect similar to that of chlorimipramine with fewer side effects. During the study some subjects were tested by Electrodermic Response to acoustic stimuli, comparing the results with the responses of patients treated with chlorimipramine. Furthermore, the plasmatic beta-endorphin level in 10 subjects treated with mianserin was compared with values found in basic conditions. The significant decrease of the plasmatic beta-endorphin level after treatment with mianserin suggests that the drug may act as an antidepressant, by varying the endorphinergic cerebral activity.

Topics: Adolescent; Adult; beta-Endorphin; Clinical Trials as Topic; Clomipramine; Depressive Disorder; Dibenzazepines; Double-Blind Method; Endorphins; Female; Humans; Male; Mianserin; Middle Aged

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

One of the main challenges in suicide prevention is the limited understanding of the biological mechanisms underlying suicide. Recent findings suggest impairments in pain processing in acutely suicidal patients. However, little is known about the biological factors that may drive these discrete physiological abnormalities. In this study, we examined plasma peptides involved in analgesic and inflammatory responses and physical pain threshold in acutely suicidal patients.. Thirty-seven depressed patients of both sexes hospitalized for severe suicidal ideation or a recent suicide attempt were characterized clinically including history of suicidal ideation and behavior. Psychological and physical pain, and pressure pain threshold was also measured. Plasma levels of β-endorphin, neurotensin, agouti-related protein (AgRP), C-reactive protein (CRP), adrenocorticotropic hormone (ACTH), and brain-derived neurotrophic factor (BDNF) were run in Milliplex multiplex assays.. The number of lifetime suicide attempts was positively correlated with β-endorphin (r = 0.702; p = 0.007), and neurotensin (r = 0.728, p = 0.007) plasma levels. Higher pain threshold was measured in the suicide attempt group as compared to the suicidal ideation group. Pain threshold was strongly and negatively associated with CRP plasma levels (r = -0.548; p < 0.001). In patients reporting chronic pain, lower AgRP levels and lower pain threshold were observed (t = 4.472; p = 0.001).. Our results suggest that abnormalities in the opioid and neurotensin systems may underlie the increase in pain threshold found in suicide attempters, and possibly risk for suicidal behavior. Targeting pain circuits and systems may provide therapeutic mechanisms for suicide prevention.

Topics: Adolescent; Adult; beta-Endorphin; Depressive Disorder; Female; Humans; Male; Middle Aged; Neurotensin; Pain Measurement; Pain Threshold; Suicidal Ideation; Suicide, Attempted; Young Adult

Preliminary data indicate that increased blood plasma level of β-endorphin in patients with nonpsychotic unipolar depression after 2 weeks of treatment correlates with the positive response to therapy. This parameter can be regarded as an objective indicator of potential improvements. Further studies aimed at determining the value of blood β-endorphin levels in patients with mood disorders for the diagnostics and estimating the therapeutic success in this disease are required.

Topics: Adult; Antidepressive Agents; beta-Endorphin; Biomarkers; Depressive Disorder; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Prospective Studies; Psychometrics; Statistics, Nonparametric; Treatment Outcome

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

beta-Endorphin (beta-EP) concentrations were measured in peripheral blood mononuclear cells of 10 elderly women with major depressive disorders, 10 age- and sex-matched healthy controls and 10 young healthy controls. beta-EP values were measured in resting condition and after stimulation with corticotropin-releasing hormone (CRH). In patients, beta-EP values were measured in drug-free condition and after 30 days of treatment with phosphatidylserine (BCPS), 200 mg/day, p.o. Basal and CRH-stimulated beta-EP concentrations were the same in patients and controls; in patients they did not change after BCPS, in spite of significant improvement of the depressive symptomatology.

Topics: Aged; Aging; beta-Endorphin; Depressive Disorder; Female; Humans; Monocytes; Phosphatidylserines

Recently it has been shown that acute administration of 200 mg L-5-hydroxytryptophan (L-5-HTP) PO may increase post-dexamethasone (DST) adrenocorticotropic hormone (ACTH) and cortisol levels in major, but not minor, depressed subjects. This study aimed to examine the effects of 200 mg L-5-HTP PO on post-DST beta-endorphin levels in the same depressed subjects. It was found that in major, but not minor, depressed subjects, L-5-HTP significantly increased post-DST beta-endorphin concentrations as compared to placebo. The L-5-HTP-induced post-DST beta-endorphin responses were significantly higher in major than in minor depressed subjects. There was a significant and positive relationship between L-5-HTP-induced post-DST beta-endorphin and ACTH or cortisol responses. There was a significant and positive relationship between L-5-HTP-induced post-DST beta-endorphin values and the Hamilton Depression Rating Scale (HDRS) score. The results show that the acute administration of L-5-HTP may increase the escape of beta-endorphin secretion from suppression by dexamethasone in major, but not minor, depression.

Topics: Adult; beta-Endorphin; Depressive Disorder; Dexamethasone; Female; Humans; Male; Middle Aged; Serotonin

1. Corticotropin-releasing hormone (ovine CRH, 100 micrograms intravenous bolus) was given to 63 unipolar depressed inpatients following the 1 mg overnight dexamethasone suppression test (DST). The depressed patients included 18 minor, 24 simple major and 21 melancholic subtypes. 2. Baseline or postdexamethasone plasma levels of intact adrenocorticotropic hormone (ACTH), beta-endorphin/beta-lipotropin (beta END/beta LPH), cortisol, and dexamethasone were measured, as well as the post DST+CRH hormone responses. 3. CRH administration 9.5 hr after dexamethasone resulted in a significant enhancement of ACTH, beta END/beta LPH and cortisol secretion. The post DST+CRH ACTH and beta END/beta LPH- but not cortisol-values exceeded their baseline hormone levels. The post DST+CRH ACTH--but not beta END/beta LPH or cortisol-levels were significantly higher in major depressives compared to minor depressives. The post DST+CRH ACTH and beta END/beta LPH--but not cortisol-levels were significantly higher in DST nonsuppressors than suppressors. The post DST+CRH ACTH levels were significantly and positively related to severity of illness. 4. The results provide evidence that the pathophysiology underlying the abnormal DST+CRH and DST tests in melancholia is localized at the pituitary level and may consist of a CRH-driven breakthrough of corticotropic cell secretion synergized by central and peripheral agents, in conjunction with a decrease in glucocorticoid feedback suppressibility.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Depressive Disorder; Dexamethasone; Hospitalization; Humans; Hydrocortisone; Middle Aged; Severity of Illness Index

To determine whether depressed patients demonstrate hypothalamic-pituitary-adrenal (HPA) axis activation during the late afternoon and evening, a time when the HPA axis is usually quiescent in normal subjects.. We administered metyrapone, an 11-beta-hydroxylase inhibitor of cortisol synthesis, to normal controls and depressed patients between 4 and 10 PM. Metyrapone blockade of cortisol secretion would amplify any HPA axis secretion.. In 10 normal control subjects, administration of metyrapone lowered plasma cortisol levels to a mean of 36 nmol/L. No rebound corticotropin or beta-endorphin secretion was seen in these normal controls between 4 and 10 PM, supporting the existence of a period of minimal endogenous corticotropin releasing factor drive. Compared with a group of placebo-treated depressed patients (n = 10), metyrapone-treated depressed subjects (n = 17) had significantly decreased plasma cortisol concentrations. However, in contrast to normal controls treated with metyrapone, metyrapone-treated depressed patients demonstrated rebound corticotroph secretion, particularly between 7:30 and 10 PM (P = .036 for patients vs normal controls for beta-endorphin secretion from 4:30 to 10 PM).. These data support the hypothesis of increased corticotropin releasing factor drive in the evening in depressed subjects and are in agreement with the longstanding observation of "early escape" from dexamethasone suppression between 4 and 11 PM in depressed patients.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Circadian Rhythm; Corticotropin-Releasing Hormone; Cortodoxone; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged; Placebos; Pyridines

To test theories that response to sleep deprivation in depression is the result of either stress reactions or down-regulation of hyperarousal, the early morning cortisol and beta-endorphin levels of depressed sleep deprivation responders and nonresponders before and after sleep deprivation were compared (areas under the curve of 8 blood samples between 7:30 and 10 a.m.). The beta-endorphin response was significantly different in responders and nonresponders, whereas all other comparisons remained nonsignificant. The results do not support theories that sleep deprivation acts as a stressor, but are not contradictory to the hyperarousal hypothesis of sleep deprivation.

Topics: Adult; Arousal; beta-Endorphin; Depressive Disorder; Down-Regulation; Humans; Hydrocortisone; Male; Psychiatric Status Rating Scales; Sleep Deprivation

A corticotropin-releasing hormone (CRH) stimulation test with four cumulative doses of human CRH (0.01, 0.06, 0.2 and 1 microgram/kg body weight) and infusion of a low dose of [Arg8]-vasopressin (0.004 U/kg body weight/30 min) was performed in five depressed patients and six healthy subjects. Plasma samples for the measurement of cortisol, ACTH and beta-endorphin were taken at regular intervals and considered as measures of pituitary-adrenal function. A dose-response relationship between CRH and the hormones measured was found in patients and controls. Depressed patients already responded to the lowest dose of CRH with respect to cortisol release, whereas ACTH and beta-endorphin responded to the second and third doses, respectively. In control subjects the cortisol and ACTH response started after the third dose of CRH, whereas beta-endorphin responded significantly to the highest dose only. When both groups were compared, differences in response were found to the higher doses of CRH with respect to cortisol, ACTH and, less markedly, beta-endorphin and to the lowest dose of CRH with respect to cortisol. Although numbers are small, the data show 'blunting' of the ACTH response to the higher doses of CRH in patients with an enhanced cortisol response of the adrenals to lower and higher doses of CRH. There was no significant difference in response when CRH was used with vasopressin as compared to treatment with CRH alone. Thus, in this design vasopressin did not contribute significantly to CRH activity. The data suggest that pituitary cell sensitivity might be changed in depression as part of HPA dysfunction.

Topics: Adrenocorticotropic Hormone; Adult; Arginine Vasopressin; beta-Endorphin; Corticotropin-Releasing Hormone; Depressive Disorder; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Infusions, Intravenous; Male; Middle Aged; Pilot Projects; Pituitary-Adrenal System; Psychiatric Status Rating Scales; Stimulation, Chemical

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

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Circadian Rhythm; Depressive Disorder; Humans; Male; Pyridines; Radioimmunoassay

Different doses dexamethasone (0.25, 0.5, and 1 mg) or cortisol (30, 60, and 120 mg) were administered PO at 2230h to 39 depressed patients and 20 healthy subjects on nonsuccessive days. The inhibiting capacity of the two steroids on hypothalamo-pituitary axis (HPA) function was evaluated by measuring the plasma levels of cortisol, ACTH, and beta-endorphin at 0900h and 1530h each day following treatment. Baseline levels of the hormones were measured before starting treatment. A dose-dependent suppressive effect of both steroids on the plasma levels of cortisol, ACTH, and beta-endorphin was found both in patients and controls, except for the 0900h levels of cortisol after cortisol treatment. The effects were most profound in the morning. Differences between patients and controls were observed after cortisol treatment, but not dexamethasone, with respect to cortisol, ACTH, and beta-endorphin plasma levels in the morning. Cortisol treatment discriminated dexamethasone nonsuppressors from suppressors (patients and controls) and patients categorized as dexamethasone suppressors from controls in a way that dexamethasone treatment could not. The data favour the idea of impaired corticosteroid feedback beyond the pituitary level as part of HPA dysfunction.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Circadian Rhythm; Depressive Disorder; Dexamethasone; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Male; Middle Aged; Personality Inventory; Pituitary-Adrenal System; Reference Values

To determine if corticotroph nonsuppression, as reflected by beta-endorphin nonsuppression, occurs before cortisol nonsuppression (defined as a cortisol level of > 140 nmol/L) when examining multiple time points in a day.. The General Medical Clinical Research Center and Inpatient Depression Research Unit, Ann Arbor, Mich.. Multiple blood samples were obtained through an intravenous catheter around the time points of 8 AM, noon, and 4 PM and assayed for beta-endorphin and cortisol.. Patients meeting Research Diagnostic Criteria for the diagnosis of major depressive disorder, primary and simple. A total of 73 subjects, both inpatients and outpatients, were studied.. Samples were obtained both at baseline and 1 day after administration of 1 mg of dexamethasone at 11:30 PM.. Overall 39 patients (53%) demonstrated beta-endorphin nonsuppression after administration of dexamethasone at any of the three time points, while only eight patients (11%) demonstrated cortisol nonsuppression at any of these time points. Cortisol nonsuppression, but not beta-endorphin nonsuppression, was associated with lower concentrations of dexamethasone in plasma. Baseline cortisol and menopausal status were significantly associated with beta-endorphin nonsuppression in women.

Topics: Adult; Age Factors; Ambulatory Care; beta-Endorphin; Circadian Rhythm; Depressive Disorder; Dexamethasone; Female; Hospitalization; Humans; Hydrocortisone; Male; Menopause; Middle Aged; Recurrence; Sex Factors

Several authors have reported attenuated adrenocorticotropin hormone (ACTH) responses to corticotropin releasing factor (CRF) administration in melancholic patients as compared with healthy controls. In order to explore the integrity of the hypothalamic-pituitary-adrenal (HPA)-axis in melancholics, we examined the following parameters in 98 subjects: the ACTH; beta-endorphin; and cortisol responses to ovine CRF (oCRF) (100 micrograms/i.v.); and the postdexamethasone cortisol values. We found significant lower CRF-induced ACTH responses in melancholic patients as opposed to healthy controls and minor depressives, while major depressives occupied an intermediate position. The psychopathological correlates of the blunted CRF-induced ACTH responses were feelings of worthlessness, self-reproach, or excessive guilt. The CRF-stimulated beta-endorphin and cortisol response did not differ between the study samples. Higher baseline plasma cortisol was associated with attenuated CRF-induced ACTH responses, but these effects were not pertinent to melancholia. There were no relationships between the disordered oCRF test results, and postdexamethasone cortisol values, age, body size, sex and severity of illness. The diagnostic power of the oCRF and the dexamethasone suppression test for melancholia is enhanced when both test results are combined.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged; Personality Inventory; Prospective Studies; Psychiatric Status Rating Scales; Reference Values

The aims of this study were to determine whether the administration of cortisol has a significant effect on mood in patients with depression and whether the effects of cortisol on changes in plasma hormone concentrations are like those of synthetic corticosteroids. Twelve patients had major depression and one each had dysthymic disorder and a depressive adjustment disorder. Five were male and nine were female. All were in-patients. Eight normal subjects, two females and six males, were used as controls. Basal beta-endorphin concentrations were 2- to 3-fold higher in depressed patients than in control subjects, but there were no significant differences between the patient and control groups in the basal (pre-infusion) plasma concentrations of ACTH, cortisol, growth hormone or prolactin. Cortisol, but not saline infusion resulted in a significant improvement in self rated mood. Surprisingly, cortisol infusion at first increased plasma beta-endorphin concentrations. At later times after cortisol infusion, plasma beta-endorphin concentrations decreased as did the plasma concentrations of ACTH and growth hormone; prolactin levels were increased. These results show (i) that cortisol infusion raises mood significantly in major depression, (ii) that plasma beta-endorphin concentration is a potential marker of major depression (iii) that rather than blunting of corticosteroid effects, responses to cortisol may even be enhanced in depressive illness. The unexpected, initial increase in beta-endorphin stimulated by cortisol, suggests that the action of cortisol is not simply one of negative feedback inhibition, but may involve mineralocorticoid, as well as glucocorticoid receptors.

Topics: Adrenocorticotropic Hormone; Adult; Affect; Antidepressive Agents; beta-Endorphin; Depressive Disorder; Female; Growth Hormone; Humans; Hydrocortisone; Infusions, Intravenous; Male; Middle Aged; Mood Disorders; Pituitary Gland; Prolactin; Psychiatric Status Rating Scales; Radioimmunoassay

Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and beta-lipotropin/beta-endorphin (beta-LPH/beta-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean [+/- SD] depressed mood score = 0.17 +/- 0.4; modified Hamilton Depression scale score = 7.6 +/- 4.5) and five as severely depressed (mean depressed mood score = 2.4 +/- 0.5; modified Hamilton Depression scale score = 15 +/- 5.6) (p < 0.05). ACTH and beta-LPH/beta-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and beta-LPH/beta-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed = 90.0 +/- 16.7; severely depressed = 34.6 +/- 8.7 (p < 0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0 mg dexamethasone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Depressive Disorder; Female; Humans; Hypothalamo-Hypophyseal System; Male; Metyrapone; Middle Aged; Neurocognitive Disorders; Personality Inventory; Pituitary-Adrenal System

Low concentrations of beta-endorphin have been found to enhance human natural killer (NK) cell activity in vitro. Both beta-endorphin and NK activity are changed by clinical depression. To evaluate whether circulating concentrations of beta-endorphin have a role in the in vivo modulation of cellular immunity in humans, we measured plasma beta-endorphin and NK cell activity in 14 depressed patients and 14 age-matched control subjects. In the depressed patients, both plasma beta-endorphin and NK cell activity were reduced to 76% and 57%, respectively, of the mean levels in the control subjects. In addition, beta-endorphin showed a significant positive correlation with lytic units of NK cell activity in the combined group of all subjects and in the patient group (p = 0.04), but not in the control group. The study supports the hypothesis that circulating endorphin is correlated with NK cell activity in vivo. This correlation may be higher in the depressed patient group.

Topics: Adult; beta-Endorphin; Cytotoxicity, Immunologic; Depressive Disorder; Female; Humans; Immune Tolerance; Immunity, Cellular; Killer Cells, Natural; Leukocyte Count; Male; Psychiatric Status Rating Scales; Psychoneuroimmunology

This study defines the pituitary B-endorphin (BE) secretory response to a low dosage (0.3 ug/kg) of human corticotropin releasing hormone (CRH) in depressed patients and normal controls pretreated with metyrapone. We find no difference in the B-endorphin response to CRH in depressed subjects without evidence of HPA overactivity, compared with controls. This finding is contrasted with other data demonstrating a blunted B-endorphin response to CRH in depressives. The influence of metyrapone pretreatment on the pituitary B-endorphin response to CRH through a mechanism that minimizes the impact of cortisol negative feedback is discussed. Future studies which include low dose CRH infusion both in the presence and in the absence of metyrapone pretreatment will help investigate alterations in the regulation of pituitary B-endorphin secretion in depression including the possibility of increased pituitary sensitivity to the negative fast feedback of cortisol.

Topics: Adrenal Glands; beta-Endorphin; Corticotropin-Releasing Hormone; Depressive Disorder; Female; Humans; Hydrocortisone; Hypothalamus; Kinetics; Male; Metyrapone; Pituitary Gland

Controversy continues over the characteristics of beta-endorphin secretion in depression. Beta-endorphin plasma levels were measured in 30 drug-free male patients with a DSM-III-R major depressive disorder and 21 healthy controls. Depressed patients displayed significantly lower beta-endorphin plasma levels in baseline conditions, after the single dose metyrapone test, and after the dexamethasone suppression test. The activation of hypothalamic-pituitary-adrenal (HPA) axis in depression might be due, at least in part, to low levels of beta-endorphin. These results suggest that HPA axis dysregulation in depression may involve peptides other than ACTH.

Topics: beta-Endorphin; Depressive Disorder; Dexamethasone; Humans; Hypothalamo-Hypophyseal System; Male; Metyrapone; Middle Aged; Pituitary-Adrenal System; Pro-Opiomelanocortin; Radioimmunoassay

Topics: Adolescent; beta-Endorphin; Child; Depressive Disorder; Female; Growth Hormone; Humans; Male; Mental Disorders; Neurosecretory Systems; Stress, Psychological; Thyrotropin

Abnormalities in plasma concentrations of beta-endorphin-like immunoreactivity (beta-endorphin) have been reported in depressed patients. This study was done to test the hypothesis that specific clinical characteristics of depression are associated with plasma beta-endorphin concentration.. Plasma beta-endorphin was evaluated in 20 depressed patients diagnosed according to DSM-III-R and in 23 age- and sex-matched comparison subjects, and each was evaluated with the structured Schedule for Affective Disorders and Schizophrenia (SADS). Twelve SADS items involving dysphoric mood and related symptoms were chosen for analysis.. Within the group of all 43 subjects and within the depressed group, beta-endorphin level correlated significantly with psychic anxiety and with phobia. In the depressed group only, beta-endorphin also correlated significantly with obsessions/compulsions. Concentration of beta-endorphin was not significantly correlated with score on the Hamilton Rating Scale for Depression or Beck Depression Inventory or with scores on other SADS symptom items, including somatic anxiety, insomnia, subjective anger, overt anger, agitation, psychomotor retardation, panic attacks, appetite loss, or total weight loss. In the group of 23 comparison subjects, beta-endorphin did not correlate with Beck or Hamilton depression score or with any of the SADS clinical variables.. High levels of plasma beta-endorphin may be associated with more severe anxiety, phobia, and obsessions/compulsions in depressed patients.

Topics: Adult; Aged; Anger; Anxiety Disorders; beta-Endorphin; Depressive Disorder; Feeding and Eating Disorders; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Phobic Disorders; Psychiatric Status Rating Scales; Psychomotor Disorders; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Weight Loss

The effect of a single dose (10 mg P.O.) of trihexyphenidyl (THP) on plasma cortisol, growth hormone (GH), and immunoreactive beta-endorphin (ir-beta-EP) was studied in seven major depressed patients and seven controls. GH secretion was suppressed (34-41%) by THP in both groups. THP did not affect cortisol secretion in depressed patients and controls. An increase (18%; p less than 0.05) in plasma ir-beta-EP levels was detected in the healthy subjects only. The results of this study do not support the hypothesized altered responsiveness to anticholinergic provocation in major depression. The inhibitory activity of THP on GH secretion indicates the involvement of the cholinergic system in the regulation of GH release in humans.

Topics: Adult; beta-Endorphin; Depressive Disorder; Female; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Neurosecretory Systems; Psychiatric Status Rating Scales; Radioimmunoassay; Trihexyphenidyl

We studied glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressed patients and controls, attempting to control for the confounding effect of endogenous glucocorticoids. After depletion of endogenous cortisol, depressed patients showed an attenuated suppressibility of corticotropin by dexamethasone in the face of unchanged dexamethasone plasma levels. Beta-endorphin levels were strongly correlated with adrenocorticotropic hormone (ACTH) concentrations. Although metyrapone administration resulted in a marked rise of glucocorticoid receptor sites per cell in controls, this effect was not present in depressives. These data support the hypothesis of a decreased glucocorticoid receptor plasticity and a partial steroid resistance in depression.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Bipolar Disorder; Depressive Disorder; Dexamethasone; Female; Homeostasis; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metyrapone; Middle Aged; Pituitary-Adrenal System; Premedication; Psychiatric Status Rating Scales; Receptors, Glucocorticoid

To investigate the relationships between pre- and postdexamethasone hypothalamic-pituitary-adrenal (HPA) axis functioning in depression, we measured the levels of baseline and postdexamethasone urinary free cortisol (UFC), plasma cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin. We found that dexamethasone significantly suppressed all hormone levels. All 4 postdexamethasone hormones--but not their baseline levels--were significantly higher in melancholic subjects than in minor and simple major depressives. We have accumulated evidence that the melancholic and minor depression groups form discrete classes in postdexamethasone HPA axis hormone levels; this supports the biological heterogeneity hypothesis of melancholia. We found that a combination of the postdexamethasone UFC and beta-endorphin values yielded the most significant diagnostic tool for melancholia. Our results suggest that the measurements of both hormones may constitute the most accurate index reflecting the HPA axis escape from suppression by dexamethasone in melancholia. By means of pathway analysis, we determined the causal relationships between age, dexamethasone circulating levels, diagnostic depression classification and the various baseline and postdexamethasone hormone values.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Depressive Disorder; Dexamethasone; Feedback; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Prospective Studies; Psychiatric Status Rating Scales; ROC Curve

A rate-sensitive fast-feedback inhibition of stress-induced corticotropin secretion by glucocorticoids is well documented in rats. Studies in patients with Cushing's disease or adrenal insufficiency have also supported the existence of fast feedback in humans. However, few studies exist in normal healthy subjects or depressed patients. This study compared fast-feedback inhibition of beta-endorphin/beta-lipotropin secretion by hydrocortisone in 16 control subjects and 16 depressed patients. A fast-feedback effect of hydrocortisone on beta-endorphin/beta-lipotropin secretion during the hour of the hydrocortisone infusion was demonstrated in control subjects. Depressed patients demonstrated no increase in beta-endorphin/beta-lipotropin concentrations during the infusion. These data suggest a decreased sensitivity to glucocorticoid fast feedback in depressed patients and complement existing studies demonstrating decreased sensitivity to proportional feedback by dexamethasone in depressed patients. We believe the data presented herein are the first demonstration that abnormal feedback occurs at the level of the brain rather than pituitary in depressed patients.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Depressive Disorder; Dexamethasone; Feedback; Female; Hippocampus; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Infusions, Intravenous; Male; Pituitary-Adrenal System; Receptors, Glucocorticoid

The CSF concentrations of CRF, somatostatin and beta-endorphin were determined in nine patients who fulfilled DSM-III criteria for major depression with psychotic features. CSF samples were obtained at baseline in the depressed state, and again after a course of ECT. Concentrations of both CRF and beta-endorphin decreased after ECT, while the concentration of somatostatin increased, although the latter difference did not attain statistical significance. The increase in CSF concentrations of CRF and beta-endorphin in depressed patients is therefore seen to be state-dependent.

Topics: Adult; Aged; beta-Endorphin; Corticotropin-Releasing Hormone; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Neuropeptides; Psychiatric Status Rating Scales; Somatostatin

Cerebrospinal fluid (CSF) beta-endorphin concentrations were determined before and after treatment in 28 patients suffering chronic neuralgic low back pain/sciatica. Nine patients carried the additional diagnosis of major depressive disorder. Pain treatment was multimodal and resulted in variable pain reduction. CSF beta-endorphin concentrations spanned a wide range with no association to age, gender, pain ratings, depressive symptomatology, and drug intake. CSF beta-endorphin concentrations were not influenced by the presence of major depressive disorder and did not change with successful treatment of pain and resolution of depression.

Topics: Adult; Aged; Back Pain; beta-Endorphin; Combined Modality Therapy; Depressive Disorder; Female; Humans; Male; Middle Aged; Pain Measurement; Sciatica; Sick Role

In order to investigate the relationship between the immune apparatus and the hypothalamic-pituitary-adrenal (HPA)-axis activity in depressed patients, we measured in vitro lymphocyte responses to the mitogens Phytohaemagglutinin (PHA), Pokeweed (PWM) and Concanavalin A (Con A) and 8 a.m. baseline cortisol values in plasma, free cortisol excretion in 24 h urine (UFC), basal and post-dexamethasone beta-endorphin values. Major depressed patients with melancholia/psychotic features exhibited a significantly lower mitogen-induced blast transformation as compared to minor and simple major depressed patients. The lymphocyte responses to the three mitogens were significantly inversely related to baseline cortisol values and postdexamethasone beta-endorphin values. The proliferative capacity of lymphocytes to stimulation with PHA and PWM was significantly and positively related to UFC excretion. Up to 45% of the variance in the immune-responses to the mitogens was explained by the baseline cortisol, post-dexamethasone beta-endorphin and UFC values.

Topics: Adult; beta-Endorphin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immune Tolerance; Lymphocyte Activation; Male; Middle Aged; Pituitary-Adrenal System; Prospective Studies

Electroconvulsive therapy is accompanied by an activation of the hypothalamic-pituitary-adrenal axis, resulting in a release of beta-endorphin from the anterior pituitary corticotrophs of humans. As a group, patients in our study demonstrated similar plasma beta-endorphin immunoreactivity response to their initial and final treatments. However, approximately half of the patients demonstrated greater beta-endorphin immunoreactivity release with their first seizure compared with their last seizure, and half of the patients demonstrated the opposite pattern. This difference was not explained by age, sex, unilateral vs bilateral treatments, sine wave vs brief pulse, or psychotropic or anticholinergic medication. Patients with constant seizure duration during the first and final treatments demonstrated a greater release of beta-endorphin immunoreactivity with the final treatment compared with the first treatment. Individuals with decreasing seizure duration during the course of the electroconvulsive therapy demonstrated a decreased beta-endorphin immunoreactivity response during their final treatment.

Topics: Adult; Aged; beta-Endorphin; Blood-Brain Barrier; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Hydrocortisone; Male; Middle Aged; Permeability; Pituitary Gland, Anterior; Radioimmunoassay; Sex Factors

The relationships between mood change, obstetric experience and alterations in plasma cortisol, beta-endorphin (beta-EP) and corticotrophin-releasing hormone (CRH) were examined in a prospective study of 97 primiparous Australian women. Psychological measures were administered between the 28th week of pregnancy and the 3rd postnatal month, including the Profile of Mood States (POMS) and the Montgomery Asberg Depressive Rating Scale (MADRS). Blood samples were collected for cortisol, beta-EP and CRH assay on most of these occasions and during labour. Factor analysis was used to identify key subsets of psychological variables for use in the subsequent analyses. 'Mood disturbance' and 'tiredness' factors peaked at 38 weeks' gestation, while 'difficulty falling asleep' was greatest around the time of birth. Cortisol, beta-EP and CRH concentrations rose significantly as pregnancy advanced and peaked at birth; plasma CRH correlated with plasma cortisol (r = 0.54) and beta-EP (r = 0.32). Women with the highest 'mood disturbance' and MADRS depression scores at 28 weeks' gestation received significantly more pain relief during labour. Those women whose mood deteriorated from 38 weeks' gestation to postnatal day 2 had larger falls in plasma beta-EP after delivery (p less than 0.01) than those women whose mood improved or remained constant. Women in this mood-deteriorated subgroup also had significantly higher MADRS depression scores at 3 months (p less than 0.01). Mild antenatal depression (MADRS greater than 13) occurred in 5.2% of women and mild postnatal depression in 4.7%. Overall, these data suggest a role for circulating CRH in the regulation of maternal cortisol secretion and significant relationships between maternal postnatal mood states and beta-EP and between antenatal mood states and obstetric events.

Topics: Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Depressive Disorder; Female; Follow-Up Studies; Humans; Hydrocortisone; Infant, Newborn; Mother-Child Relations; Personality Tests; Pilot Projects; Pregnancy; Pregnancy Complications; Prospective Studies; Puerperal Disorders

Baseline beta-endorphin and cortisol levels and their responses to 1 mg dexamethasone were measured in 11 healthy controls and in 35 depressed patients, categorized according to the DSM-III. Dexamethasone significantly suppressed beta-endorphin levels. Depressed patients with melancholia/psychotic features exhibited significantly increased post-dexamethasone beta-endorphin levels compared with healthy controls, minor and simple major depressives; the baseline beta-endorphin levels did not differ between those study samples. Post-dexamethasone beta-endorphin and cortisol values were found to be significantly and positively correlated. Accordingly, cortisol non-suppressors showed significantly higher post-dexamethasone beta-endorphin levels. Post-dexamethasone beta-endorphin may be the most sensitive and specific reflection of the disorder in negative feedback exerted by dexamethasone in depression.

Topics: Adult; beta-Endorphin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales

Studies in depression using a maximal stimulatory dose of corticotropin releasing factor have concluded that elevated resting cortisol levels in depressed patients exert a negative feedback effect on the corticotroph, resulting in a decreased corticotropin response. In this preliminary report, we examine the effects of a submaximal dose of corticotropin releasing factor on the release of another corticotroph secretory product, beta-lipotropin-beta-endorphin. We observed a decreased beta-lipotropin-beta-endorphin response in depressed subjects, but a normal adrenal cortisol response. Although the total beta-lipotropin-beta-endorphin response was decreased, the initial secretory response did not differ between patients and normal controls. Rather, the patients appeared to turn off secretion faster. This rapid shutoff was seen in all patients regardless of resting cortisol levels, suggesting that resting cortisol levels alone do not explain the decreased response seen in depressed patients.

Topics: Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Depressive Disorder; Dose-Response Relationship, Drug; Feedback; Humans; Hydrocortisone; Male

Circulating levels of cortisol and beta-endorphin were evaluated in basal condition and following dexamethasone administration in 20 healthy subjects and in 60 subjects suffering from hyperphagic obesity. Moreover, mental tests were administered to these subjects in order to evaluate the affective state. Our data showed that in obese patients B-Ep plasma levels were significantly higher than those of the control group, while cortisol plasma levels were similar in the two groups. Dexamethasone administration decreased cortisol plasma levels in normal and obese subjects, while did not modify B-Ep plasma levels in obese subjects. However, after dexamethasone administration 16.6% of the obese subjects did not show a complete decrease of cortisol level. This group of subjects obtained the highest scores for depression and hypochondria to MMPI.

Topics: Adult; beta-Endorphin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Hyperphagia; Male; Obesity

The dexamethasone suppression test (DST) has been suggested as an effective tool for differentiating between depression and dementia. After administering 1 mg dexamethasone, we measured cortisol, ACTH, and beta-endorphin levels in 32 nondepressed patients with idiopathic Parkinson's disease (PD) (14 also with dementia) and 20 healthy, age-matched controls. Four of the 20 controls, 9 of the 18 with PD alone, and 8 of the 14 with PD and dementia were dexamethasone nonsuppressors (cortisol value greater than or equal to 5 micrograms/100 ml). PD patients without dementia (nonsuppressors) showed higher basal plasma values of cortisol (22.06 +/- 5.30 micrograms/100 ml) compared with the suppressors (13.38 +/- 3.30 micrograms/100 ml). Plasma ACTH and beta-endorphin responded in a coupled way to dexamethasone challenge. Higher basal levels of both peptides were found among PD patients (demented and nondemented), nonresponders to DST. Thus, the DST does not appear to be effective in differentiating between depression and dementia in PD. In addition, PD nonsuppressors showed higher basal values of plasma ACTH, beta-endorphin, and cortisol (similar to patients with major depression). This suggests that although the depression is clinically undetectable, both disorders may share some pathophysiological features at the hypothalamic hypophyseal adrenal level.

Topics: Adrenocorticotropic Hormone; Aged; beta-Endorphin; Corticotropin-Releasing Hormone; Dementia; Depressive Disorder; Dexamethasone; Diagnosis, Differential; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Parkinson Disease; Personality Tests

Previous research in neuroendocrinology has evidenced that hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) depends on hypersecretion of corticotropin-releasing hormone (CRH). The aim of this study was to investigate the activity of HPA before and after recovery in depressed patients treated with electroconvulsive therapy (ECT). An h-CRH-stimulation test was performed on 2 occasions with examination of the HPA axis before ECT treatment during episodes of major depressive disorders with melancholia, and during the recovery phase after treatment. The results showed that patients during depression had significantly higher plasma levels of cortisol at 15 and 30 min after h-CRH-administration than after recovery. Depressed patients had significantly higher plasma levels of beta-endorphin 30 min after h-CRH-stimulation. The results are in agreement with previous studies, which have shown hypercortisolemia during depression. A possible hypersecretion of CRH may explain the effect on cortisol and beta-endorphin. No significant differences were found between cumulative responses of corticotropin, cortisol and beta-endorphin, calculated as the areas under the concentration curves.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Corticotropin-Releasing Hormone; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Time Factors

Topics: Adult; Agoraphobia; beta-Endorphin; Depressive Disorder; Fear; Female; Humans; Infusions, Intravenous; Lactates; Lactic Acid; Male; Panic; Phobic Disorders

An alpha-theta brainwave biofeedfack training program was applied as a novel treatment technique for chronic alcoholics. Following a temperature biofeedback pretraining phase, experimental subjects completed 15 30-min sessions of alpha-theta biofeedback training. Compared to a nonalcoholic control group and a traditionally treated alcoholic control group, alcoholics receiving brainwave training (BWT) showed significant increases in percentages of EEG record in alpha and theta rhythms, and increased alpha rhythm amplitudes. Alcoholics receiving BWT showed a gradual increase in alpha and theta brain rhythms across the 15 experimental sessions. These experimentally treated alcoholics showed sharp reductions in self-assessed depression (Beck's Depression Inventory) compared to the control groups. Alcoholics receiving standard medical treatment (abstinence, group psychotherapy, antidepressants) showed a significant elevation in serum beta-endorphin levels at the conclusion of the experiment. This neuropeptide is an index of stress and a stimulant of caloric (e.g., ethanol) intake. Application of brainwave treatment, a relaxation therapy, appears to counteract the increase in circulating beta-endorphin levels seen in the control group of alcoholics. 13-month follow-up data indicate sustained prevention of relapse in alcoholics that completed alpha-theta brainwave training.

Topics: Alcoholism; Alpha Rhythm; beta-Endorphin; Biofeedback, Psychology; Depressive Disorder; Electroencephalography; Follow-Up Studies; Humans; Psychiatric Status Rating Scales; Socioeconomic Factors

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Depressive Disorder; Dexamethasone; Humans; Melanocyte-Stimulating Hormones; Peptides

Since the discovery of CRH in 1981, several investigators have reported abnormalities of the hypothalamic-pituitary-adrenal (HPA) system in response to direct stimulation of the corticotroph cells in patients with psychiatric disorders. To further explore HPA system integrity in major depressive disorders, 13 drug-free patients and normal subjects matched for age, sex, ovarian status, and body weight received 100 micrograms synthetic human CRH as an iv bolus dose. Compared to that in the normal subjects, in the depressed patients a significant attenuation of the net ACTH release after CRH administration (772 +/- 597 vs. 263 +/- 286 pmol/min.L; P less than 0.02) was observed, while beta-endorphin and cortisol responses did not differ significantly between the groups. The magnitudes of ACTH and cortisol release were negatively correlated in the patient group only (r = -0.67; P less than 0.01). Thus, the blunted ACTH response to CRH in depression might be related to hypercortisolemia, while the implications of the apparent dissociation of ACTH and beta-endorphin after CRH administration still remain unclear. Our data support the hypothesis that the hyperactivity of the HPA system in depression most likely is a consequence of CRH hypersecretion, the origin of which may be explained by abnormal central glucocorticoid receptor or neurotransmitter regulation.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Depressive Disorder; Female; Humans; Kinetics; Male; Middle Aged; Radioimmunoassay; Reference Values

In the past, some researchers found increased cortisol and prolactin responses to the administration of fenfluramine in major-depressed patients. It was believed that the fenfluramine test could prove to constitute another challenge probe to reflect the central serotonergic function. The present study was conducted in order to investigate the pituitary/adrenal responses to fenfluramine in major- versus minor-depressed patients. To this end we administered 60 mg D,L-fenfluramine p.o. to 40 depressed patients categorized according to the DSM-III. The basal levels of cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphins and prolactin and their levels 2 and 4 h after fenfluramine administration were measured. We found no significant effect for fenfluramine treatment on cortisol, ACTH or beta-endorphins. There was a significant (p = 0.02) effect for fenfluramine treatment on prolactin. The enhanced secretion of prolactin was only significant (p = 0.006) in major (296.X2, 296.X3, 296.X4) and not in minor (300.40, 309.00) depressives. It was concluded that our findings corroborate the thesis of a hypersensitive serotonergic neurotransmission during a major depressive episode.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Brain; Depressive Disorder; Female; Fenfluramine; Humans; Hydrocortisone; Male; Middle Aged; Prolactin; Prospective Studies; Psychiatric Status Rating Scales; Serotonin

Topics: Adjustment Disorders; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Bipolar Disorder; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged

The time course study of the endorphin response to electroconvulsive therapy (ECT) was carried out in 10 patients (including one control who did not receive active ECT) at the first and sixth ECT. Results showed a significant rise of plasma endorphin levels after ECT. This increase returned to the pre-ECT level within 1 hr after ECT. There was a pre-rise of plasma endorphin level, which probably was stress related and which was also observed in the control case.

Topics: beta-Endorphin; Depressive Disorder; Electroconvulsive Therapy; Humans; Radioimmunoassay

The effect of a single dose (60 mg p.o.) of the serotonin agonistic agent fenfluramine (FNF) on plasma cortisol, prolactin (PRL), growth hormone (GH), and immunoreactive beta-endorphin (ir-beta-EP) levels was assessed in eight major depressed patients and eight controls. The hormones were monitored at basal level (0') and hourly during 5 h following FNF administration. The pharmacological challenge caused an elevation of 80% in PRL secretion in the healthy controls and only 42% in the depressed patients. However, the actual prolactin response (delta max) failed to discriminate depressed patients from controls. A blunted response followed by a decrease (33%) in serum cortisol levels was observed in depressed patients 5 h after drug administration while an increase of 94% was obtained in controls after 3 h. FNF provocation did not affect GH and ir-beta-EP plasma levels. The blunted cortisol responsiveness to FNF administration in depressed patients may reflect functional hypoactivity of central serotonergic system at least during the acute phase of major depression. It is not clear why the cortisol hyporesponsivity in depressed patients is not accompanied by a similar reduced PRL response to FNF challenge.

Topics: Adult; beta-Endorphin; Depressive Disorder; Female; Fenfluramine; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Prolactin; Radioimmunoassay

Basal serum cortisol, growth hormone, prolactin and immunoreactive (IR) plasma beta-endorphin levels were measured in 31 depressed patients (14 endogenous, 17 nonendogenous) undergoing the dexamethasone suppression test. The endogenously depressed patients had significantly higher (22.55 +/- 1.34 micrograms/dl) predexamethasone cortisol levels than the nonendogenous patients (16.34 +/- 1.93 micrograms/dl). The mean serum prolactin and growth hormone values of these two groups were not significantly different, while plasma IR-beta-endorphin levels of the endogenous group (40.11 +/- 3.57 pg/ml) were significantly lower than those of the nonendogenous group (120.33 +/- 27.98 pg/ml). Neither group showed a significant correlation between plasma IR-beta-endorphin and serum cortisol values. These results indicate that measurement of predexamethasone serum cortisol values and plasma IR-beta-endorphin could be valuable laboratory tests in the diagnosis of depression.

Topics: Adult; beta-Endorphin; Depressive Disorder; Dexamethasone; Female; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Prolactin

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

Plasma levels of beta-endorphin plus beta-lipotropin were determined in 35 hospital patients with depression and in 23 controls before and after administration of 1 mg of dexamethasone (dxm). Dxm suppressed opioid secretion in both groups. The opioid levels of the patients were significantly higher than those of the controls both before and after dxm. All the controls were cortisol suppressors. Among the patients the post-dxm opioid levels of cortisol nonsuppressors (n = 14) were higher than those of cortisol suppressors (n = 21). A significant correlation between the opioid and cortisol levels was found in the patients. There was a significant association between the use of neuroleptics and high opioid levels, but the difference between the patients and the controls was not explained by the effect of any single class of drugs. The results support the concept of hypersecretion of corticotropin-releasing factor in depression.

Topics: Adult; beta-Endorphin; beta-Lipotropin; Depressive Disorder; Dexamethasone; Endorphins; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Psychotropic Drugs

The effects of single and repeated electroconvulsive treatment (ECT) on beta-endorphin (beta-EP), cortisol, growth hormone (GH) and prolactin (Prl) plasma levels were investigated in nine depressed patients. Blood samples were monitored a day before ECT, the day of the first and sixth ECT (0, 30, 60 and 90 min after seizures), the day afterwards and 4 weeks after termination of the ECT course. A significant elevation of beta-EP levels was achieved immediately with and 24 h after the first and the sixth ECT. A transient increase in basal beta-EP was observed 1 day following the sixth ECT in comparison with pre-treatment level. Peak and 30 min levels of cortisol were increased compared with baseline by the first ECT. The former (peak) but not the latter (30 min) were increased also at the sixth treatment. GH levels were decreased the day after the first ECT in comparison with the pre-treatment levels and immediately following each ECT in comparison with baseline. A trend toward elevation of Prl was observed immediately after the first and sixth ECT, although the rise did not reach significant levels. ECT administration stimulated beta-EP and cortisol secretion and suppressed human GH release, possibly by activation of endorphinergic and/or serotonergic systems. These mechanisms might be involved in the beneficial effect of ECT in depression.

Topics: Adult; beta-Endorphin; Depressive Disorder; Electroconvulsive Therapy; Endorphins; Female; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Prolactin

The hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in many patients with depression, probably at all levels of the axis. To determine if HPA dysregulation is associated with severity of depression, we studied a group of 66 patients with major depressive disorder. Each patient underwent a pretreatment Dexamethasone Suppression Test, with plasma postdexamethasone cortisol determination at 8:00 AM, 4:00 PM, and 11:00 PM. All three postdexamethasone cortisol levels were significantly correlated with the Hamilton Rating Scale for Depression (HRSD) scores. We also examined the "profile" measures of mean, maximum, and minimum of the three cortisol values; again, all three were significantly correlated with HRSD scores. To evaluate associations between clinical severity and HPA dysregulation at the pituitary level, we studied a second group of 44 patients with major depressive disorder. Each had postdexamethasone cortisol determinations at 4:00 PM and 11:00 PM as well as pre- and postdexamethasone beta-endorphin determinations at 4:00 PM. The cortisol data from this group followed the same pattern as in the first sample, and there was a significant relationship between HRSD score and degree of beta-endorphin nonsuppression as well. These results suggest that severity of depression is one of the determinants of dysregulation at both adrenal and pituitary levels of the HPA axis, accounting for 10%-20% of the observed variance.

Topics: Adult; beta-Endorphin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Psychiatric Status Rating Scales

We studied 27 patients who complained of pain, for which no organic basis could be found, and 11 patients without pain. All patients were depressed according to clinical diagnosis and Beck Depression Inventory (BDI) scores. Plasma beta-endorphin levels were found not to differ between the two groups or across other variables. The patients who complained of pain had significantly higher scores on the BDI.

Topics: Adolescent; Adult; Aged; beta-Endorphin; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Pain; Sensory Thresholds

Plasma cortisol, ACTH and beta endorphin were measured before and after dexamethasone in 8 severely depressed patients and 8 age- and sex-matched controls to examine the relationship of ACTH and endogenous opioids to cortisol in depression. Despite having significantly higher plasma levels of cortisol than the controls, the depressed patients did not have correspondingly elevated plasma levels of ACTH. Beta-endorphin levels were also similar in the two groups. All three hormones suppressed to some degree after dexamethasone, but cortisol suppressed less in patients than controls. Our findings suggest that in severe depressive illness abnormalities exist in the hypothalamic-pituitary-adrenal axis peripherally as well as centrally.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Depressive Disorder; Dexamethasone; Endorphins; Female; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged

Topics: Adolescent; Adult; Anorexia Nervosa; beta-Endorphin; beta-Lipotropin; Circadian Rhythm; Clonidine; Depressive Disorder; Desipramine; Dexamethasone; Endorphins; Female; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Norepinephrine; Pituitary-Adrenal System; Receptors, Adrenergic

There are indications to suggest a relationship between low levels of 5-hydroxy-indoleacetic acid (5HIAA) in the cerebrospinal fluid and suicidal behavior. Many depressed patients show an elevated cortisol secretion. As beta-endorphin is derived from the same precursor as ACTH, it is expected that plasma beta-endorphin levels will also rise in depressed patients. We report here a case of severe depression with diurnal variation who showed low CSF 5HIAA prior to his suicide. In contrast, his catecholamine metabolites were 50% above the mean values of other depressed patients. Hormonal measurements, however, showed low cortisol, prolactin and beta-endorphin levels.

Topics: beta-Endorphin; Catecholamines; Circadian Rhythm; Depressive Disorder; Endorphins; Homovanillic Acid; Humans; Hydrocortisone; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Middle Aged; Prolactin; Suicide

Topics: Adult; beta-Endorphin; Bipolar Disorder; Depressive Disorder; Endorphins; Female; Humans; Male; Middle Aged; Somatostatin

This study addresses the question of whether pituitary peptides (ie, beta-endorphin) show regulatory disruption in endogenous depression and, if so, does it co-occur in the same subjects who show cortisol dysregulation. Endogenously depressed patients and psychiatric controls from three centers were evaluated, when not taking medications, and studied for plasma cortisol and beta-endorphin levels. Plasma samples were taken at four time points over one hour, on the basal day, and 16 hours after 1 mg of dexamethasone. From 33% to 69% of the endogenous patients were abnormal in their postdexamethasone cortisol levels, and from 50% to 69% were abnormal on postdexamethasone beta-endorphin values (vs 0% and 8%, respectively, for controls). When endogenous subjects were evaluated for abnormality on both cortisol and beta-endorphin, after dexamethasone, it was found that the two measures of hypothalamic-pituitary-adrenal dysfunction did not necessarily co-vary. In fact when having either abnormal beta-endorphin or cortisol levels (or both) was used as a biological marker a larger number of the endogenous patients were detected than with either measure alone. Our conclusions are as follows: Plasma beta-endorphin shows a circadian rhythm similar to that seen with corticotropin (ACTH) and is suppressable by dexamethasone. In many endogenous patients plasma beta-endorphin levels escape from dexamethasone suppression. Many of these subjects are not cortisol escapers. When abnormality of either the beta-endorphin or cortisol is considered it is clear that both levels of the hypothalamic-pituitary-adrenal axis can be dysregulated in endogenous depression.

Topics: Adolescent; Adult; Aged; beta-Endorphin; beta-Lipotropin; Depressive Disorder; Dexamethasone; Endorphins; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System

In order to assess whether a central hypothalamic impairment could account for the pro-opiomelanocortin (POMC)-related peptide over-secretion in depressive disorders, plasma B-lipotropin (B-LPH), B-endorphin (B-EP) and cortisol concentrations were measured in 9 patients affected by neurotic depression: every 4 h over a 24-h period; in response to insulin-induced hypoglycaemia (0.1 IU/kg body weight), and during dexamethasone (DXM) administration (0.5 mg X 4/day for 2 days). Eight age-matched healthy volunteers (controls) were also studied. B-EP and B-LPH were determined by specific radioimmunoassays after plasma extraction and gel chromatography. Compared with the controls, the patients showed a 3 times higher plasma B-EP, twice the normal B-LPH levels, and a 20% cortisol increase. The neurotic depressed patients showed and evening-related decrease in the levels of the 3 hormones, expressed as mean values, similar to that in the controls, whereas the single cosinor analysis revealed a significant circadian rhythm of B-LPH and B-EP only in 3 and 2 patients, respectively. Insulin-induced hypoglycaemia (ITT) stimulated the release of B-LPH and cortisol in both groups, whereas the B-EP increase was absent in the patients. DXM reduced plasma cortisol and B-LPH levels in controls and patients, but in the latter it failed to reduce the B-EP concentrations. The present data indicate that neurotic depressed patients are characterized by increased activity of the hypothalamic-pituitary-adrenal axis, with maintained circadian rhythmicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; beta-Endorphin; beta-Lipotropin; Blood Glucose; Circadian Rhythm; Depressive Disorder; Dexamethasone; Endorphins; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary-Adrenal System; Pro-Opiomelanocortin

Anomalous anterior pituitary hormone responses to acute administration of TRH and LRH have previously been observed in patients with primary affective disorders (PAD), with TRH eliciting GH, FSH and LH rises, and LRH eliciting GH and Prl rises. We examined whether the same unusual responses were present also for beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) in 15 PAD patients, in 9 patients with secondary affective disorders (SAD), and in 7 controls. TRH (500 micrograms iv) elicited rises of beta-EP plasma levels in 5 PAD and 2 SAD patients, and of beta-LPH in 4 PAD and 3 SAD patients. LRH (150 micrograms iv) elicited rises of plasma beta-EP levels in 2 PAD and 2 SAD patients, and of beta-LPH in 5 PAD and 2 SAD patients. No rises of beta-EP and beta-LPH plasma levels were observed in PAD patients after saline administration, nor in the controls after TRH, LRH or saline administration.

Topics: Adult; Aged; beta-Endorphin; beta-Lipotropin; Bipolar Disorder; Depressive Disorder; Endorphins; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Luteinizing Hormone; Middle Aged; Pituitary Hormones, Anterior; Prolactin; Thyrotropin-Releasing Hormone

Plasma and cerebrospinal fluid (CSF) levels of ACTH, B-lipotropin (B-LPH) and B-endorphin (B-EP) were simultaneously measured in 10 patients with major depression (35-57 yr) with a disease history of 10-34 yr, 7 of them with recurrent episodes, and in 13 age-matched healthy controls. In patients, lumbar puncture was performed after a 10 days drug-free period. Plasma B-EP and B-LPH levels were measured by RIA after silicic acid plasma extraction and Sephadex G-75 column chromatography. Plasma ACTH concentrations were measured by IRMA. For CSF assays the extraction step was avoided. In depressed patients, plasma ACTH (16.2 +/- 6.9 fmol/ml, mean +/- SD), B-LPH (19.8 +/- 8.5) and B-EP (17.8 +/- 7.0) levels were significantly higher (p less than 0.01) than in controls. On the contrary, CSF levels of the three peptides were similar in the two groups. No correlations were found between plasma or CSF concentrations and duration of the disease or severity of the actual episode. These data add further evidence to the independent regulation between central and peripheral POMC-related peptides. They also reduce the possibility that peptides of pituitary origin, directly from the gland or through the peripheral circulation, could penetrate the CSF.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Depressive Disorder; Endorphins; Female; Humans; Male; Middle Aged

Eight obese patients (exceeding ideal body weight by 50% or more) with no endocrinological or metabolic disorders and 8 healthy, age-matched, normal-weight volunteers were submitted to an overnight short dexamethasone (DXM) suppression test and to a psychological assessment through various psychometric scales. Plasma B-Endorphin (B-EP), B-Lipotropin (B-LPH), ACTH and cortisol concentrations were evaluated in basal conditions, as well as 9 and 17 hours after late night administration of 1 mg DXM in both groups. All hormones were measured by radioimmunoassay, either directly in the plasma (ACTH and cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-LPH and B-EP). In obese patients, plasma B-EP levels in basal conditions were three times higher than in normal weight controls and remained unaltered by DXM suppression. ACTH and B-LPH, in contrast, were within the normal range and were significantly reduced by DXM. In 3 of the 8 patients, plasma cortisol concentrations at 17 hours post-DXM were greater than 50 ng/ml indicating an early escape from the suppression. Psychometric evaluations revealed a prevalence of depressive personality in obese patients. These data indicate an hypersecretion of B-EP in obese patients, which is only partially dependent on hypothalamic control.

Topics: Adrenocorticotropic Hormone; Adult; Affect; beta-Endorphin; beta-Lipotropin; Depressive Disorder; Dexamethasone; Endorphins; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Obesity; Pituitary-Adrenal System

Efforts to elucidate the abnormal mechanism of corticotropin and beta-endorphin in major depression have yielded conflicting findings. The relationship of plasma levels of cortisol, corticotropin, and beta-endorphin in 42 patients with a Research Diagnostic Criteria diagnosis of major depression, endogenous subtype was examined. Following the DST, 32 patients were nonsuppressors and 10 were suppressors. The differences between the median values for plasma corticotropin and beta-endorphin immunoreactivity were not significant at any time of measurement after the DST.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Depressive Disorder; Dexamethasone; Endorphins; Hospitalization; Humans; Hydrocortisone; Middle Aged; Psychiatric Status Rating Scales

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Depressive Disorder; Endorphins; Humans; Hypothalamo-Hypophyseal System; Pituitary Gland; Pituitary-Adrenal System

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

Rate-sensitive inhibition of ACTH release is abnormal in Cushing's disease but uncharacterized in depression. The authors found that two of 10 depressed patients had paradoxical responses, suggesting the existence of a hypothalamic-pituitary-adrenal axis abnormality in depression that is independent of dexamethasone suppression test results.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Depressive Disorder; Dexamethasone; Endorphins; Feedback; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System

Plasma cortisol levels of 28 hospitalized patients meeting Research Diagnostic Criteria for major or nonmajor (minor or intermittent) depression were significantly higher than those of eight normal subjects. In contrast, plasma beta-endorphin immunoreactivity was significantly lower in patients with nonmajor depression than in those with major depression or in normal subjects. A low ratio of plasma beta-endorphin to cortisol immunoreactivity was found to characterize patients in both groups. Through the use of only this ratio, a post-hoc analysis identified 25 depressed patients and seven controls. These findings have implications for psychiatric diagnosis and the involvement of the endogenous opioid system in the pathogenesis of depression.

Topics: Adult; Age Factors; beta-Endorphin; Borderline Personality Disorder; Depressive Disorder; Endorphins; Female; Hospitalization; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Lipoproteins, LDL; Male; Pituitary-Adrenal System

Topics: Aged; beta-Endorphin; Depressive Disorder; Electroconvulsive Therapy; Endorphins; Female; Humans; Male

Immunoreactive (ir) plasma beta-endorphin level was assayed in ten symptomatic patients with a unipolar major depressive disorder and in 16 psychiatrically normal controls matched for age and sex. Plasma ir-beta-endorphin level in depressed patients was similar to that in controls. All depressed patients was similar to that in controls. All depressed patients had a transient, approximately threefold increase in ir-beta-endorphin after each use of electroconvulsive therapy (ECT). The increase of plasma ir-beta-endorphin level after ECT parallels the transient elevation of adrenocorticotropic hormone level reported by others and probably reflects a hypothalamic response to ECT.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Depressive Disorder; Electroconvulsive Therapy; Endorphins; Female; Humans; Hypothalamus; Male; Middle Aged; Radioimmunoassay

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

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; beta-Lipotropin; Depressive Disorder; Desipramine; Endorphins; Female; Follicle Stimulating Hormone; Growth Hormone; Humans; Luteinizing Hormone; Male; Methoxyhydroxyphenylglycol; Middle Aged; Mood Disorders; Pituitary Gland, Anterior

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Depressive Disorder; Endorphins; Female; Humans; Hydrocortisone; Menopause; Middle Aged

Morning plasma concentrations of beta-endorphin immunoreactivity were significantly higher in a group of depressed patients meeting the Research Diagnostic Criteria for Major Depressive disorder or Schizo-affective disorder, depressed, than in age- and sex-matched groups of normal controls and psychiatric patients without affective disorders. Furthermore, physostigmine-stimulated release of beta-endorphin immunoreactivity was also significantly greater in the depressed patients. These results provide the first evidence for elevated plasma concentrations of beta-endorphin in depression and also represent further evidence for cholinergic supersensitivity in depression. These results suggest that elevated plasma concentrations of beta-endorphin and cholinergically stimulated hypothalamic-pituitary beta-endorphin release, might potentially represent biological state or trait markers for depression.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Depressive Disorder; Double-Blind Method; Endorphins; Humans; Physostigmine; Psychotic Disorders; Random Allocation; Receptors, Cholinergic

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: Adult; Affective Disorders, Psychotic; Aged; beta-Endorphin; Depressive Disorder; Dexamethasone; Electroconvulsive Therapy; Endorphins; Female; Humans; Hydrocortisone; Lipoproteins, LDL; Male; Middle Aged; Radioimmunoassay

We investigated the relationship between hypothalamic-pituitary-adrenal (HPA) activity, as measured by 24-hour mean urinary free cortisol (MUFC), and cerebrospinal fluid (CSF) opioid activity in patients with major affective disorder and normal volunteers. Among depressed patients, but not normal volunteers, mean 24-hour urinary cortisol values were significantly correlated with CSF opioid activity measured by radioreceptor assay, but were not significantly correlated with beta-endorphin immunoreactivity measured by radioimmunoassay. MUFC, as expected, was significantly higher in depressed patients than in normal volunteers. Mean values of CSF opioid activity and beta-endorphin immunoreactivity did not differ significantly in the two groups. The positive opioid-MUFC correlation found in the depressed group appeared to depend on patients who were cortisol hypersecretors. These data, using relatively crude measures of cortisol and opioid activity, are suggestive of a relationship between these two systems, particularly under "activated" conditions such as those observed in depression.

Topics: Adult; beta-Endorphin; Bipolar Disorder; Depressive Disorder; Endorphins; Female; Humans; Hydrocortisone; Male; Radioimmunoassay; Radioligand Assay; Receptors, Opioid

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