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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) and its related family members are implicated in stress-related disorders such as anxiety and depression. Recently, two new members of this neuropeptide family have been discovered in the brain: urocortin II (also known as stresscopin-related peptide) and urocortin III (also known as stresscopin). These urocortins are selective agonists for the CRF(2) receptor, show a distinct neuroanatomical localization and are involved in stress-coping responses such as anxiolysis. Thus, CRF, the urocortins and their receptors form an intricate network in the brain involved in the acute phase as well as the recovery phase of the stress response.
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PMID:Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression. 1178 5

Abnormal signaling at corticotropin-releasing factor CRF1 and CRF2 receptors might contribute to the pathophysiology of stress-related disorders such as anxiety, depression and eating disorders, in addition to cardiac and inflammatory disorders. Recently, molecular characterization of CRF1 and CRF2 receptors and the cloning of novel ligands--urocortin, stresscopin-related peptide/urocortin II, and stresscopin/urocortin III--have revealed a far-reaching physiological importance for the family of CRF peptides. Although the physiological roles of the CRF2 receptor remain to be defined, the preclinical and clinical development of specific small-molecule antagonists of the CRF1 receptor opens new avenues for the treatment of psychiatric and neurological disorders.
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PMID:The CRF peptide family and their receptors: yet more partners discovered. 1183 Feb 63

The aim of this cohort study conducted in France in 1997-1998 was to investigate the effects of antenatal anxiety and depression on spontaneous preterm labor. A consecutive series of 634 pregnant women with singleton pregnancies was included. Anxiety and depression were assessed using self-administered questionnaires: Spielberger's State-Trait Anxiety Inventory and the Edinburgh depression scale. Depression scores were dichotomized with a cutoff value suggestive of major depression. The 75th percentile was used for anxiety scores. A logistic regression analysis, controlling for sociodemographic and biomedical factors and including interaction terms, revealed that depression was positively associated with the outcome among underweight women, defined as women with a prepregnancy body mass index below 19 (adjusted odds ratio (OR) = 6.9, 95% confidence interval (CI): 1.8, 26.2). A similar result was observed for trait anxiety in women with a history of preterm labor (adjusted OR = 4.8, 95% CI: 1.1, 20.4). The association was close to significance for state anxiety in women with vaginal bleeding (adjusted OR = 3.6, 95% CI: 0.9, 14.7). These findings show that anxiety and depression, when combined with specific biomedical factors, are associated with spontaneous preterm labor. A synergic action of psychological and biomedical factors on the secretion of placental corticotropin-releasing factor is hypothesized.
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PMID:Role of anxiety and depression in the onset of spontaneous preterm labor. 1183 92

Current treatments for depression are inadequate for many individuals, and progress in understanding the neurobiology of depression is slow. Several promising hypotheses of depression and antidepressant action have been formulated recently. These hypotheses are based largely on dysregulation of the hypothalamic-pituitary-adrenal axis and hippocampus and implicate corticotropin-releasing factor, glucocorticoids, brain-derived neurotrophic factor, and CREB. Recent work has looked beyond hippocampus to other brain areas that are also likely involved. For example, nucleus accumbens, amygdala, and certain hypothalamic nuclei are critical in regulating motivation, eating, sleeping, energy level, circadian rhythm, and responses to rewarding and aversive stimuli, which are all abnormal in depressed patients. A neurobiologic understanding of depression also requires identification of the genes that make individuals vulnerable or resistant to the syndrome. These advances will fundamentally improve the treatment and prevention of depression.
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PMID:Neurobiology of depression. 1193 38

Stress-associated disorders such as melancholic depression are characterized by persistent hypothalamic-pituitary-adrenocortical (HPA) axis activation and intensive anxiety. Corticotropin-releasing hormone (CRH) appears to play an essential role in pathophysiology of such disorders. In an attempt to elucidate possible mechanisms underlying persistent activation of CRH in the central nervous system (CNS), we examined responses of hypothalamic and extrahypothalamic CRH systems to the stressors (immobilization stress or psychological stress) and interactions between these CRH systems and glucocorticoids in rats. We propose multiple feedback loops activating central CRH system: (1) attenuation of glucocorticoid-induced negative feedback on the activity of the hypothalamic and brainstem nuclei during chronic stress, (2) autoregulation of CRH biosynthesis in the hypothalamic paraventricular nucleus (PVN) through up-regulation of Type-1 CRH receptor (CRHR-1), and (3) glucocorticoid-mediated positive effects on the amygdaloid CRH system. Stress initially activates the hypothalamic CRH system, resulting in the hypersecretion of glucocorticoids from the adrenal gland. In addition, the psychological component of the stressor stimulates the amygdaloid CRH system. In the chronic phase of stress, down-regulation of GR in the PVN and other brain structures such as the locus coeruleus (LC) fails to restrain hyperfunction of the HPA axis, and persistent activation of the HPA axis further up-regulates the amygdaloid CRH system. Thus, the hypothalamic and the amygdaloid CRH systems cooperatively constitute stress-responsive, anxiety-producing neurocircuitry during chronic stress, which is responsible for the clinical manifestations of stress-associated disorders. Effects of tricyclic antidepressants (TCAs), which appear to mitigate the above mentioned multiple feedback loop forming the vicious circle to activate central CRH systems, will also be discussed.
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PMID:Multiple feedback mechanisms activating corticotropin-releasing hormone system in the brain during stress. 1207 34

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key biological abnormalities described in major depressive disorder, occurring in 30-50% of depressed subjects. Corticotropin-releasing hormone (CRH) and vasopressin (AVP) are the main regulators of this stress system, with the two neuropeptides acting synergistically in bringing about adrenocorticotropin (ACTH) release from the anterior pituitary and cortisol from the adrenal gland. Based on the demonstration of elevated cerebrospinal fluid levels of CRH in depressives, and other evidence, it has been postulated that excess CRH and the resultant increased HPA forward drive form the basis of neuroendocrine dysregulation in depression. However, there is an accumulating body of evidence to support a significant role for AVP in the regulation of pituitary-adrenal activity in health and also in depressive disorder. This review, based on a Medline search from 1980 to 2001, focuses on the functional neuroanatomy, receptor pharmacology, VP synergism with CRH, and the data from clinical and pre-clinical studies that support an important role for AVP in the pathophysiology of major depression. We suggest that future antidepressants may target the vasopressinergic system.
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PMID:Vasopressin as a target for antidepressant development: an assessment of the available evidence. 1220 Feb 2

Corticotropin-releasing factor (CRF) is the major regulator of the hypothalamic-pituitary-adrenal (HPA) axis, and plays a key role in coordinating the endocrine, as well as autonomic and behavioral responses of an organism to stress. Direct CNS administration of CRF to laboratory animals produces an aggregate of effects that mimic the mammalian stress response. Impeding CRF function with CNS administration of a peptidergic CRF antagonist can block these manifestations of the stress response whether produced by exogenous CRF or occurring naturally in response to a stressor. A role for hypersecretion of CRF in the pathophysiology of depression is suggested by the finding that CNS administration of CRF mirrors many of the signs and symptoms utilized as diagnostic criteria for major depression. In addition, a large body of clinical evidence points to excess hypothalamic secretion of CRF and an accompanying HPA axis hyperactivity in patients with major depression. The recent development of selective, small molecule CRF(1) receptor antagonists, which block the effects of CRF both in vitro and in vivo, suggest that these compounds may be effective in the treatment of affective and anxiety disorders. Early evidence indicates that these agents possess anxiolytic and antidepressant activity in animal behavioral models. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:Are CRF receptor antagonists potential antidepressants? 1240 2

Many patients with major depression show evidence of over-activation of the hypothalamic - pituitary - adrenal axis (HPA), as evidenced by hypercortisolism and adrenal hyperplasia. Such over-activity is associated with increased corticotropin releasing factor (CRF) reactivity in the CSF and blunted release of ACTH in response to CRF infusion. Recent evidence suggests a switch from CRF to AVP regulation of the axis during depression, with depressed patients showing enhanced response to ddAVP infusion. The HPA provides multiple potential sites for antidepressant development. The use of glucocorticoid antagonists, cortisol synthesis inhibitors, CRF and AVP antagonists have been suggested. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:Novel approaches to the treatment of depression by modulating the hypothalamic - pituitary - adrenal axis. 1240 3

There have been considerable advances in neurobiology in recent years that are providing new directions for the development of novel classes of antidepressants. For example, the finding that corticotropin-releasing factor (CRF) is hypersecreted in depressed patients and mediates certain symptoms of depression has led to the development of specific antagonists of the CRF(1) receptor. These are expected to prove highly effective for the treatment of mood and anxiety disorders. Another related avenue of research is based on evidence that cortisol is integral to the pathophysiology of major depression with psychotic features. One alternative for treating this subtype of affective disorder is, therefore, to block the action of glucocorticoids using a receptor antagonist such as mifepristone. These are just two of the many new directions that will likely lead to the development of antidepressants in the near future.
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PMID:New directions in the development of antidepressants: the interface of neurobiology and psychiatry. 1240 64

Corticotropin-releasing hormone (CRH) plays a major role in coordinating the behavioral, endocrine, autonomic and immune responses to stress. CRH and CRH-related peptides and their receptors are present in the central nervous system and in a wide variety of peripheral tissues, including the immune, cardiovascular and reproductive systems, and have been associated with the pathophysiology of many disease states. These observations have led to the development of several CRH receptor type-selective antagonists, which have been used experimentally to elucidate the role of CRH and related peptides in physiological and disease processes, such as anxiety and depression, sleep disorders, addictive behavior, inflammatory and allergic disorders, neurological diseases and pre-term labor. Because of the complex network of multiple CRH receptor subtypes and their tissue- and agonist-specific signaling diversity, antagonists need to be developed that can target specific CRH receptor isoform-driven signaling pathways.
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PMID:Functional characteristics of CRH receptors and potential clinical applications of CRH-receptor antagonists. 1243 40


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