Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corticotropin-releasing factor (CRF) is the principal neuropeptide involved in regulating the stress response. When centrally administered to animals it produces somatic changes analogous to those seen in both depression and anxiety. In humans, it is capable of reproducing the hormonal changes which are characteristically seen in depressed patients. A literature search using Medline, Embase Psychiatry, PsycLIT and BIDS from 1996-1997 revealed 25 studies that have examined CRF concentrations in patients with affective disorder. The methodology of these studies varies and they can be criticised, in particular, for failing to consider the stress response of the lumbar puncture. Recently, post-mortem immunocytochemical techniques have been employed to help clarify the nature of these abnormalities in depression. On balance, evidence from CSF sampling, post-mortem findings and dynamic endocrine studies suggests that both hypothalamic and extra-hypothalamic concentrations of CRF are moderately elevated in a proportion of currently antidepressant treatment, high CRF concentrations tend to normalise. The causes of increased CRF output in depression are also unknown but may involve an integration of remote vulnerability factors and recent stressors perhaps mediated through impaired function of glucocorticoid receptors. Ultimately, the careful manipulation of CRF may hold therapeutic promise for sufferers of mood disorders.
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PMID:The role of corticotropin releasing factor in depressive illness: a critical review. 966 25

Exposure of rats to long-term intermittent walking stress results in a persistent inactive behavior in the subsequent two weeks in about 50% of rats (depression-model rats) while the activity returns gradually toward baseline in other rats (spontaneous recovery rats). To explore the role of hypothalamic-pituitary-adrenal (HPA) axis in these depression-model rats, we examined changes in the gene expression of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in the paraventricular nucleus (PVN) of the hypothalamus using in situ hybridization histochemistry. We imposed the intermittent walking stress for two weeks in male Wistar rats, then compared the response of the depression-model rats and spontaneous recovery rats. The expression of CRF mRNA in PVN increased significantly by 60% and 80% compared to controls, in the model and the recovery rats, respectively. The magnocellular AVP mRNA in PVN increased significantly in the model rats by 60% compared to controls. The concentration of plasma ACTH increased in the model rats, but no significant change in plasma corticosterone or AVP level was noted in all three groups. Our results suggest that increased magnocellular AVP in PVN plays an important role in the regulation of HPA axis of the depression-model rats induced by long-term walking stress.
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PMID:Increased expression of magnocellular arginine vasopressin mRNA in paraventricular nucleus of stress-induced depression-model rats. 966 61

The hypothalamic-pituitary-adrenal axis exerts profound, multilevel inhibitory effects on the female reproductive system. Corticotropin-releasing hormone (CRH) and CRH-induced proopiomelanocortin peptides inhibit hypothalamic gonadotropin-releasing hormone secretion, whereas glucocorticoids suppress pituitary luteinizing hormone and ovarian estrogen and progesterone secretion and render target tissues resistant to estradiol. The hypothalamic-pituitary-adrenal axis is thus responsible for the "hypothalamic" amenorrhea of stress, which is also seen in melancholic depression, malnutrition, eating disorders, chronic active alcoholism, chronic excessive exercise, and the hypogonadism of the Cushing syndrome. Conversely, estrogen directly stimulates the CRH gene promoter and the central noradrenergic system, which may explain adult women's slight hypercortisolism; preponderance of affective, anxiety, and eating disorders; and mood cycles and vulnerability to autoimmune and inflammatory disease, both of which follow estradiol fluctuations. Several components of the hypothalamic-pituitary-adrenal axis and their receptors are present in reproductive tissues as autacoid regulators. These include ovarian and endometrial CRH, which may participate in the inflammatory processes of the ovary (ovulation and luteolysis) and endometrium (blastocyst implantation and menstruation), and placental CRH, which may participate in the physiology of pregnancy and the timing of labor and delivery. The hypercortisolism of the latter half of pregnancy can be explained by high levels of placental CRH in plasma. This hypercortisolism causes a transient postpartum adrenal suppression that, together with estrogen withdrawal, may partly explain the depression and autoimmune phenomena of the postpartum period.
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PMID:Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. 969 32

Stress produces a reduction in the amplitude of some circadian rhythms. The neurochemical mechanisms underlying stress-induced changes in circadian rhythms are not known. To investigate a possible role of corticotropin-releasing factor (CRF) in this phenomenon, three related experiments were carried out: activity rhythms of male golden hamsters (10/14 hours light/dark entrained, lights on at 0800 h) were measured 1) following the intracerebroventricular administration of CRF (0.5, 1.0, 2.0, or 4.0 microg) at two different times of day, 2) following social stress (30-min resident-intruder confrontation), 3) and following the administration of the CRF-antagonist alpha-helical CRF9-41 (2.0 microg) prior to a 15-min resident-intruder confrontation. CRF produced a significant, dose-related decrease in circadian rhythm amplitude following administration in the morning hours, but not in the afternoon. CRF also induced transient increases in activity post injection concomitant with an activation of the hypothalamic-pituitary-adrenocortical (HPA) system. Stress similarly reduced the amplitude of activity patterns and stimulated the HPA system. The stress-induced depression of circadian rhythm amplitude was significantly attenuated following alpha-helical CRF9-41. These data suggest a role for CRF in the stress-related modulation of circadian locomotor rhythm amplitude.
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PMID:Effects of corticotropin-releasing factor on circadian locomotor rhythm in the golden hamster. 970 Sep 69

Over the past several years, remarkable advances have been made both in our understanding of the central nervous system (CNS) and in the pathophysiology of the major psychiatric disorders, resulting in major break-throughs in our capacity to treat these devastating illnesses. Since the seminal work of Ramon Y Cajal and Golgi at the turn of the century, new techniques such as fluorescence histochemistry have evolved into immunohistochemical and more recently in situ hybridization. These techniques have permitted, for the first time, the elucidation of chemically defined neural circuits. Such advances in the mapping of neural systems and the visualization of monoaminergic and peptidergic neurons and their receptors in tissue sections have provided the tools for the burgeoning field of neurochemical pathology of psychiatric disorders. Data provided from such studies has served as the basis for the development of novel pharmacological approaches to the treatment of affective and anxiety disorders, as well as schizophrenia. This review focuses on two major neural systems implicated in the pathophysiology of depression, serotonin and corticotropin-releasing factor (CRF). Development of novel agents are described including selective serotonin receptor agonists, combined selective serotonin receptor antagonists and serotonin reuptake inhibitors, CRF receptor antagonists, and the use of an antisense strategy.
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PMID:Psychopharmacology of affective disorders in the 21st century. 978 75

Corticotropin-releasing factor (CRF), a 41 amino acid-containing peptide, appears to mediate not only the endocrine but also the autonomic and behavioral responses to stress. Stress, in particular early-life stress such as childhood abuse and neglect, has been associated with a higher prevalence rate of affective and anxiety disorders in adulthood. In the present review, we describe the evidence suggesting that CRF is hypersecreted from hypothalamic as well as from extrahypothalamic neurons in depression, resulting in hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevations of cerebrospinal fluid (CSF) concentrations of CRF. This increase in CRF neuronal activity is also believed to mediate certain of the behavioral symptoms of depression involving sleep and appetite disturbances, reduced libido, and psychomotor changes. The hyperactivity of CRF neuronal systems appears to be a state marker for depression because HPA axis hyperactivity normalizes following successful antidepressant treatment. Similar biochemical and behavioral findings have been observed in adult rats and monkeys that have been subjected to early-life stress. In contrast, clinical studies have not revealed any consistent changes in CSF CRF concentrations in patients with anxiety disorders; however, preclinical findings strongly implicate a role for CRF in the pathophysiology of certain anxiety disorders, probably through its effects on central noradrenergic systems. The findings reviewed here support the hypothesis that CRF receptor antagonists may represent a novel class of antidepressants and/or anxiolytics.
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PMID:The role of corticotropin-releasing factor in depression and anxiety disorders. 985 71

Depressive disorder rates in stimulant-dependent individuals are substantially higher than community rates. Further, depressive symptoms are considered a major component of stimulant withdrawal. The comorbidity of these disorders may reflect shared neurochemical alterations in the function of serotonin, dopamine, and peptide systems, such as corticotropin releasing factor (CRF) and neuropeptide Y (NPY). These alterations are observed in patients, and in animal models of depression and stimulant dependence, particularly in limbic brain structures. This shared neurobiology does not seem to result from significant shared heritability or genetic linkage; stimulants may induce changes in neurobiology that are similar to those found in depression, and these changes might provide a therapeutic target. Stimulant-dependent patients with a depressive disorder may be a specific subpopulation for antidepressant trials, and they might reduce their stimulant abuse when treated with antidepressants. Nevertheless, concomitant dependence on alcohol or opioids may influence this response, and antidepressants appear to be more effective for depression in combined stimulant and opioid dependence than in combined stimulant and alcohol dependence.
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PMID:Depression and stimulant dependence: neurobiology and pharmacotherapy. 986 11

Bilateral olfactory bulbectomy in the rat produces a well-characterized syndrome that is independent of anosmia. This syndrome is reversed by chronic antidepressant administration, which provides the basis for the olfactory bulbectomy model of depression. The present experiments focused on neuropeptide plasticity in central olfactory/limbic structures following olfactory bulbectomy in rats. Male Sprague-Dawley rats received bilateral surgical ablation of the olfactory bulbs, sham surgery, or no surgery and were killed either three, seven, 14 or 28 days later. Relative levels of messenger RNA encoding neuropeptide Y, somatostatin, thyrotropin-releasing hormone, and corticotropin-releasing factor precursors in the forebrain were measured by quantitative in situ hybridization histochemistry using oligonucleotide probes. Prepro-neuropeptide Y messenger RNA levels in the piriform cortex and dentate gyrus were significantly elevated in bulbectomized rats 14 and 28 days after surgery compared to sham-operated and surgically naive rats. Prepro-somatostatin messenger RNA levels in the piriform cortex were marginally increased in bulbectomized rats at these time-points. Thyrotropin-releasing hormone and corticotropin-releasing factor precursor messenger RNA levels were not altered in the brain regions studied. The results indicate that olfactory bulbectomy causes long-term increases in the expression of the neuropeptide Y gene. These findings suggest that neuropeptide Y plasticity in the olfactory/limbic system may contribute to the olfactory bulbectomy syndrome in rats, and they provide further evidence of a role for neuropeptide Y in the pathophysiology of depression.
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PMID:Effects of olfactory bulbectomy on neuropeptide gene expression in the rat olfactory/limbic system. 988 71

Neuropeptides: corticotropin releasing factor (CRF), neuropeptide Y (NPY) and somatostatin (STS) have been associated with depression and anxiety, while neurotensin (NT), calcitonin gene-related peptide (CGRP) and tachykinins [neurokinin A (NKA) and substance P (SP)] are presumed to also play a role in the function of the dopaminergic system. Moreover, investigations in the past decade have shown that psychotomimetics and antipsychotic drugs as well as lithium affect brain synthesis, tissue concentrations, and release of some neuropeptides. In view of the above, experiments were carried out to explore whether changes in neuropeptides constitute one of the mechanisms of action of electroconvulsive treatment (ECT). Human cerebrospinal fluid (CSF) was studied before and after ECT, and brains from healthy and models of depression rats were investigated in electroconvulsive stimuli (ECS)-treated and sham-treated animals. The major findings were that a series of ECTs, in parallel to clinical recovery, increased CSF concentrations of NPY-like immunoreactivity (-LI), STS-LI, and CRF-LI, and in one study endothelin-LI. A series of ECS, but not a single treatment, reproducibly elevated concentrations of NPY-LI, NKA-LI, and STS-LI--but not NT-LI, SP-LI, galanin-LI, or CGRP-LI--in hippocampus, frontal cortex, and occipital cortex. No changes were measured in other regions, e.g., striatum. NPY and STS mRNAs were also increased indicating that ECS affects peptide synthesis. Generalized seizures induced by, e.g., kainic acid or pentylenetetrazole, had similar effects on neuropeptides. The changes persisted for at least 1 week after the last treatment. Pretreatment with compounds reducing seizures, such as benzodiazepines and MK-801; had no effect on magnitude of neuropeptide changes although the seizure duration was decreased by > 50%. On the basis of these findings, it is suggested that neuropeptides are involved in ECT's mechanisms of action. Since ECT is therapeutically efficient in both schizophrenia and depression and, taking into account that antipsychotic drugs and psychotomimetics as well as lithium selectively affect some neuropeptides, it is hypothesized that distinct combinations of neuropeptide and monoamine changes in selected neuronal populations constitute the underpinnings of ECT's effects on specific disease symptoms, conceivably independent of diagnosis.
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PMID:Neuropeptides and electroconvulsive treatment. 1018 19

Chronic pelvic pain (CPP) is a frequent and often unexplained gynecological complaint. We attempted to evaluate stress history, psychological features and hypothalamic-pituitary-adrenal (HPA) axis function in a group of patients suffering from CPP associated with pelvic adhesions. We recruited 10 patients with CPP and adhesions and 14 painfree, infertile control patients who underwent gynecological examination and diagnostic laparoscopy in a general hospital. Psychological assessment included structured interviews on sexual and physical abuse experiences and major life events as well as questionnaires on pain characteristics and depression. To evaluate HPA axis function, we measured plasma adrenocorticotropin (ACTH) and salivary cortisol responses to the administration of 100 micrograms human corticotropin-releasing factor (CRF). Results revealed high, but not statistically increased, prevalence rates of sexual and physical abuse for patients with CPP and adhesions as compared to controls. Patients with CPP and adhesions reported a significantly higher total number of major life events. Mean depression scores were normal in both groups. Patients with CPP and adhesions demonstrated normal plasma ACTH, but decreased salivary cortisol levels in the CRF stimulation test. These preliminary findings suggest that stress and neuroendocrine changes may also contribute to the pathophysiology of CPP with an identified organic correlate.
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PMID:Psychological and endocrine correlates of chronic pelvic pain associated with adhesions. 1021 83


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