beta-endorphin and Depressive-Disorder--Major

A role for beta-endorphin (beta-END) in the pathophysiology of major depressive disorder (MDD) is suggested by both animal research and studies examining clinical populations. The major etiological theories of depression include brain regions and neural systems that interact with opioid systems and beta-END. Recent preclinical data have demonstrated multiple roles for beta-END in the regulation of complex homeostatic and behavioural processes that are affected during a depressive episode. Additionally, beta-END inputs to regulatory pathways involving feeding behaviours, motivation, and specific types of motor activity have important implications in defining the biological foundations for specific depressive symptoms. Early research linking beta-END to MDD did so in the context of the hypothalamic-pituitary-adrenal (HPA) axis activity, where it was suggested that HPA axis dysregulation may account for depressive symptoms in some individuals. The primary aims of this paper are to use both preclinical and clinical research (a) to critically review data that explores potential roles for beta-END in the pathophysiology of MDD and (b) to highlight gaps in the literature that limit further development of etiological theories of depression and testable hypotheses. In addition to examining methodological and theoretical challenges of past clinical studies, we summarize studies that have investigated basal beta-END levels in MDD and that have used challenge tests to examine beta-END responses to a variety of experimental paradigms. A brief description of the synthesis, location in the CNS and behavioural pharmacology of this neuropeptide is also provided to frame this discussion. Given the lack of clinical improvement observed with currently available antidepressants in a significant proportion of depressed individuals, it is imperative that novel mechanisms be investigated for antidepressant potential. We conclude that the renewed interest in elucidating the role of beta-END in the pathophysiology of MDD must be paralleled by consensus building within the research community around the heterogeneity inherent in mood disorders, standardization of experimental protocols, improved discrimination of POMC products in analytical techniques and consistent attention paid to important confounds like age and gender.

Topics: Animals; Behavior; beta-Endorphin; Brain; Depressive Disorder, Major; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Serotonin

Interactions between serotonergic and the endogenous opioid systems have been suggested to be involved in the etiopathogenesis of depression and in the mechanism of action of antidepressants. Activation of serotonin 5-HT1A receptors has been shown to increase plasma beta-endorphin (beta-END) levels in animal studies and in healthy humans.. To assess interaction abnormalities between 5-HT1A receptors and the endogenous opioid system in patients with major depression and the possible modulating effect of citalopram.. The beta-END response to the 5-HT1A receptor agonist, buspirone (30 mg), was measured in 30 patients with major depression and in 30 age- and sex-matched healthy controls before and after an 8-week treatment with citalopram. Pre-treatment score of the Hamilton Rating Scale for Depression (HRSD) was >or=17. Antidepressant response was defined by a 50% decrease in the HRSD. Pre- and post-treatment maximum peak response (Deltamax) and the area under the curve (AUC) of beta-END response were compared. Three time points were measured (60, 90 and 120 min). We also examined the correlations between the beta-END response and the antidepressant response. Buspirone plasma levels were not measured.. At baseline, beta-END response was similar in patients and controls. After 8 weeks of citalopram treatment depressed patients showed a significant decrease in the beta-END response (Deltamax: p<.001; AUC: p<.001). A significant correlation between the beta-END reduction in the response and the reduction in the HRSD score (r=.656; p<.001) was observed.. Changes in interaction between 5-HT1A receptor system and the endogenous opioid system may play a role both in the mechanism of action and response to antidepressant drugs.

Topics: Adolescent; Adult; beta-Endorphin; Buspirone; Case-Control Studies; Citalopram; Depressive Disorder, Major; Female; Humans; Immunoradiometric Assay; Male; Middle Aged; Receptor, Serotonin, 5-HT1A; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Severity of Illness Index; Statistics, Nonparametric; Time Factors; Young Adult

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

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

Activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS) and aberrations in endogenous opioids play a role in the pathophysiology of major depressive disorder (MDD). There are no studies which examined the associations between both systems in MDD. The aim of the present study was to examine the relation between β-Endorphin (β-EP), Endomorphin-2, and their mu-opioid receptor (MOR) as well as interleukin (IL)-6 and IL-10, an anti-inflammatory cytokine, in MDD patients.. The study included 60 depressed drug-free male patients and 30 matched controls. Serum β-EP, Endomorphin-2, MOR, IL-6 and IL-10 levels were measured using ELISA techniques.. The results revealed a significant increase in serum β-EP, MOR, IL-6 and IL-10 in MDD patients versus healthy controls. MOR levels were strongly associated with IL-10 levels. There were no significant correlations between endogenous opioids and IL-6 and IL-10.. The results show that MOR levels may function as a possible component of the CIRS whilst there is no evidence that β-EP and EM-2 may modify the IRS. The significant correlation between MOR levels and IL-10 may be explained through central activation of the HPA-axis and increased B-cell numbers expressing MOR as a response to cytokine over-secretion in MDD.

Topics: Adult; beta-Endorphin; Case-Control Studies; Depression; Depressive Disorder, Major; Humans; Interleukin-10; Male; Oligopeptides; Receptors, Opioid, mu

This study examined unique versus shared stress and pain-related phenotypes associated with premenstrual dysphoric disorder (PMDD) and prior major depressive disorder (MDD). Sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA)-axis measures were assessed at rest and during mental stress, as well as sensitivity to cold pressor and tourniquet ischemic pain tasks in four groups of women: (1) non-PMDD with no prior MDD (N=18); (2) non-PMDD with prior MDD (N=9); (3) PMDD with no prior MDD (N=17); (4) PMDD with prior MDD (N=10). PMDD women showed blunted SNS responses to stress compared to non-PMDD women, irrespective of prior MDD; while women with prior MDD showed exaggerated diastolic blood pressure responses to stress versus never depressed women, irrespective of PMDD. However, only in women with histories of MDD did PMDD women have lower cortisol concentrations than non-PMDD women, and only in non-PMDD women was MDD associated with reduced cold pressor pain sensitivity. These results suggest both unique phenotypic differences between women with PMDD and those with a history of MDD, but also indicate that histories of MDD may have special relevance for PMDD.

Topics: Adult; Analysis of Variance; beta-Endorphin; Blood Pressure; Chi-Square Distribution; Cold Temperature; Depressive Disorder, Major; Enzyme-Linked Immunosorbent Assay; Female; Heart Rate; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Mathematics; Middle Aged; Neuropsychological Tests; Norepinephrine; Pain Measurement; Phenotype; Premenstrual Syndrome; Progesterone; Rest; Speech; Surveys and Questionnaires; Sympathetic Nervous System; Tourniquets; Young Adult

Psychological, endocrine and immune parameters were measured over a 6-month period in 14 healthy subjects who underwent an unpredictable acute emotional stress (e.g. sudden death of a loved one) compared with 14 controls who did not. Probands were profoundly stressed as assessed 10 days after bereavement by their scores on the Hamilton Rating Scales of Anxiety and Depression, adrenocorticotropin and cortisol plasma concentrations, and non-suppression in response to dexamethasone. Functional alterations of immune parameters, such as responsiveness of peripheral blood lymphocytes to mitogens, were found 40 days after bereavement. Despite a normal number of circulating lymphocyte subsets, the functional activity of natural killer (NK) cells was markedly reduced at day 40. Changes in the intracellular concentration of beta-endorphin in peripheral blood mononuclear cells correlated with anxiety and depression scores. Controls showed no changes in psychometric, endocrine and immune measures during the 6-month study. Cluster analysis revealed two groups of bereaved subjects with different patterns of immune and endocrine changes: (1) Five subjects, characterized by harm-avoidant temperament and long-lasting dysphoric mood, showed reduced responsiveness of peripheral blood lymphocytes to mitogens, decreased NK cell activity and non-suppression in response to dexamethasone that persisted for 6 months. (2) Nine subjects showed significant changes only during the early phase after bereavement. Our data suggest that the immunological consequences of stress do not simply overlap with psychological and endocrine alterations, and are particularly severe and long-lasting in a subgroup of subjects, indicating the importance of individual variability in the capacity to cope with stress.

Topics: Adaptation, Psychological; Adolescent; Adult; Aged; Anxiety; Bereavement; beta-Endorphin; Cluster Analysis; Depressive Disorder, Major; Dexamethasone; Female; Glucocorticoids; Humans; Hydrocortisone; Killer Cells, Natural; Lymphocytes; Male; Middle Aged; Mitogens; Surveys and Questionnaires; Time Factors

We have preliminarily investigated the hypothesis that sugar consumption may impact the prevalence of major depression by correlating per capita consumption of sugar with the prevalence of major depression. Major depression prevalence data (annual rate/100) was obtained from the Cross-National Epidemiology of Major Depression and Bipolar Disorder study [Weissman et al., 1996]. Sugar consumption data from 1991 was obtained from the Food and Agricultural Organization of the United Nations. For the primary analysis, sugar consumption rates (cal/cap/day) were correlated with the annual rate of major depression, using the Pearson correlation coefficient. For the six countries with available data for the primary analysis, there was a highly significant correlation between sugar consumption and the annual rate of depression (Pearson correlation 0.948, P=0.004). Naturally, a correlation does not necessarily imply etiology. Caveats such as the limited number of countries with available data must be considered. Although speculative, there are some mechanistic reasons to consider that sugar consumption may directly impact the prevalence of major depression. Possible relationships between sugar consumption, beta-endorphins, and oxidative stress are discussed.

Topics: beta-Endorphin; Cross-Sectional Studies; Depressive Disorder, Major; Dietary Sucrose; Energy Intake; Humans; Oxidative Stress; Prevalence

Plasma cortisol, beta-endorphin, corticotropin, corticotropin-releasing factor, and salivary cortisol concentrations, resting and after ingestion of 1 mg of dexamethasone, were investigated in depressed patients and controls.. Fourteen outpatients from the psychiatric department diagnosed with depressive disorder (ICD-10 Classification) participated in the study. The comparison group consisted of 12 healthy volunteers from the hospital staff. All hormones were measured using direct iodine-125 radioimmunoassay, except corticotropin-releasing factor, which included a sample preextraction and concentration step.. The basal plasma cortisol and corticotropin-releasing factor levels in depressive disorder were significantly higher than in the healthy group. After dexamethasone administration, corticotropin-releasing factor plasma values decreased significantly in the depressed group, but showed no significant changes in the controls. In depressive disorder baseline values correlated significantly for salivary cortisol and plasma cortisol, salivary cortisol and plasma corticotropin-releasing factor and plasma corticotropin and beta-endorphin. Similar correlations were found in the healthy subjects, except for salivary cortisol and plasma corticotropin-releasing factor.. These findings indicate that the increased corticotropin-releasing factor plasma concentrations demonstrated in depressive disorder reflect the hypothalamic corticotropin-releasing factor hypersecretion evidenced in this illness. Therefore, measurements of plasma corticotropin-releasing factor levels can be considered a reliable tool for investigating the role of this peptide in the pathophysiology of depression.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Corticotropin-Releasing Hormone; Depressive Disorder, Major; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged; Reference Values; Saliva

In patients with major depression, abnormalities in baseline cortisol secretion and resistance to negative feedback are well established. However, it is unclear if patients with major depression have alterations in the hypothalamic-pituitary-adrenal (HPA) response to stressors. While other challenges to the HPA axis have used endocrine stimuli such as insulin-induced hypoglycemia, we now report of the response to a social stressor in patients with major depression and matched control subjects. We used the Trier Social Stress Test (TSST), a public speaking task followed by mental arithmetic challenge in front of a panel of judges. The results suggest that depressed patients manifest normal cortisol response to a social stressor, despite increased pre-stressor plasma cortisol. However, the beta-endorphin response to the TSST was significantly smaller in the depressed patients compared to matched controls. These data are similar to data found with exogenous corticotropin-releasing-hormone challenge studies and suggest that elevated baseline cortisol can modulate the pituitary corticotroph response to a stressor, but that changes in adrenal sensitivity to ACTH result in a robust cortisol response to this stressor.

Topics: Adult; Analysis of Variance; beta-Endorphin; Case-Control Studies; Depressive Disorder, Major; Female; Humans; Hydrocortisone; Male; Middle Aged; Social Behavior; Stress, Psychological