UMLS:C0011570 - FACTA Search

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)

The sleep apnea syndrome (SAS), which is defined by more than 5 apneas or hypopneas per hour of sleep (9), is quite a frequent affection which concerns 1.4 to 10% of general population (1.7). The major daytime complaints of the SAS are daytime sleepiness, memory and attention disorders, headaches and asthenia especially in the morning, and sexual impotence (9). The nocturnal manifestations are dominated by sonorous and generally long standing snoring, increased by dorsal decubitus and intake of alcohol, with repeated interruptions by respiratory arrests. These manifestations are always noted but rarely spontaneously reported. The sleep, non refreshing, is agitated and perturbed by numerous awakenings. The findings of the clinical examination are poor: obesity is found in 2/3 of the cases and arterial hypertension in 1/2 of the cases (20). Polygraphic recording during sleep only permits an absolute diagnosis. This frequent affection is a real problem of public health because of its numerous complications (3, 10, 12, 13, 18, 21). Symptoms of depression are often found when a patient with a SAS is examined and conversely, symptoms which evoke a SAS can be found in the clinical examination of depressed patients. We decided so to study the thymic and anxious status of 24 patients investigated for a SAS and submitted to a polygraphic recording during sleep. Four clinical parameters were studied: DSM III-R diagnosis criteria, Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HARS) and thymasthenia rating scale of Lecrubier, Payan and Puech. We also reported Total Sleep Time (TST = 6.5 +/- 1.5), Apnea Hypopnea Index (AHI = 26.7 +/- 21.6), number (2.1 +/- 2.8/h) and duration (174.2 +/- 150.8 s/h) of hypoxic events. Results showed that among 24 patients, 8 were depressed according to DSM III-R diagnosis criteria and had MADRS > 25, 22 were anxious, 11 had a major anxiety (HARS > 15) and 15 presented thymasthenia (SET > 15). Significative correlations existed between anxiety and depression (r = 0.82; p < 0.0001), depression and thymasthenia (r = 0.77; p < 0.0001) and thymasthenia and anxiety (r = 0.75; p < 0.0001). Among the 8 depressed patients a correlation existed between AHI and depression (r = 0.72; p = 0.04), but no correlation was found between depression and hypoxic events. These results were comparable to those of Guilleminault (10), Reynolds (21), Kales (12), Bliwise (3), Klonoff (13) and Millman (18) who studied relations between SAS and depression. The evaluation of thymasthenia gave a more precise typology of the depressive state associated to SAS: the type of the mood disorder is more "blunted" and "anhedonic" than "sorrowful", particularly characterised by asthenia, lack of energy, reduction of interests (leisures, libido, work), loss of initiative, difficulties to organise tasks, fall of performances and reduction of pleasure usually felt in pleasant events (15). The physic symptomatology dominated the psychic one. The sleep disorganization, more than metabolic consequences of apneas, could be involved in this associated depressive state. Other neuropsychiatric troubles can be associated to the SAS. In fact, cognitive troubles (2, 8, 14, 16, 19, 22, 24) and personality disorders (12, 18) have been described. Our data confirm previous observations suggesting a frequent association between SAS, depression, fatigue and anxiety. Clinicians should consequently be aware that a depression with severe complaints of fatigue should deserve an investigation oriented towards SAS. Conversely, when a SAS is diagnosed, it is necessary to look for a possible depression in order to set up the most appropriate treatment. The frequency of SAS, like depression's one, increases with age. Prescription and consummation of sedative psychotropic drugs increase too with age. Since respiratory depressant effects of these drugs have been clearly demonstrated, it is important to evoke SAS when depressive and/or anxious states are diagnosed and not to aggravate it. An efficacious treatment of SAS can also cure the associated depressive state, but this one can persist. It is necessary, in this case, to select a non sedative antidepressant.
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PMID:[Depressive symptomatology and sleep apnea syndrome]. 1240 78

Since its introduction almost 20 years ago, the tail suspension test has become one of the most widely used models for assessing antidepressant-like activity in mice. The test is based on the fact that animals subjected to the short-term, inescapable stress of being suspended by their tail, will develop an immobile posture. Various antidepressant medications reverse the immobility and promote the occurrence of escape-related behaviour. This review focuses on the utility this test as part of a research program aimed at understanding the mechanism of action of antidepressants. We discuss the inherent difficulties in modeling depression in rodents. We describe how the tail suspension differs from the closely related forced swim test. Further, we address some key issues associated with using the TST as a model of antidepressant action. We discuss issues regarding whether it satisfies criteria to be a valid model for assessing depression-related behavioural traits. We elaborate on the tests' ease of use, strain differences observed in the test and gender effects in the test. We focus on the utility of the test for genetic analysis. Furthermore, we discuss the concept of whether immobility maybe a behavioural trait relevant to depression. All of the available pharmacological data using the test in genetically modified mice is collated. Special attention is given to selective breeding programs such as the Rouen 'depressed' mice which have been bred for high and low immobility in the tail suspension test. We provide an extensive pooling of the pharmacological studies published to date using the test. Finally, we provide novel pharmacological validation of an automated system (Bioseb) for assessing immobility. Taken together, we conclude that the tail suspension test is a useful test for assessing the behavioural effects of antidepressant compounds and other pharmacological and genetic manipulations relevant to depression.
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PMID:The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. 1589 Apr 4

Vasopressin and corticotropin releasing factor (CRF) are both critical regulators of an animal's stress response and have been linked to anxiety and depression. As such, antagonists of the CRF1 and V1b receptor subtypes are being developed as potential treatments for affective disorders. The two most characterized V1b and CRF1 antagonists are SSR149415 and CP-154,526, respectively, and the present studies were designed to compare these two compounds in acute animal models of affective disorders. We employed five anxiety models: Separation-induced pup vocalizations (guinea pig and rat), elevated plus-maze (EPM), conditioned lick suppression (CLS), and marble burying (mouse); as well as three depression models: forced swim test (FST; mouse and rat) and tail suspension test (TST; mouse). SSR149415 (1-30 mg/kg) was active in the vocalization, EPM and CLS models, but inactive in marble burying. CP-154,526 (1-30 mg/kg) was active in vocalization models, but inactive in EPM, CLS, and marble burying. SSR149415 was inactive in all depression models; CP-154,526 was active in rat FST but inactive in mouse models. This work demonstrates the different profiles of V1b and CRF1 receptor antagonists and supports both approaches in the treatment of affective disorders.
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PMID:Comparison of the V1b antagonist, SSR149415, and the CRF1 antagonist, CP-154,526, in rodent models of anxiety and depression. 1729 71

Dysregulation of the serotonergic signaling system has been implicated in the pathology of mood disorders including depression, and various rodent models of disrupted serotonergic signaling display depression-related behavioral phenotypes. Depression is a common neuropsychiatric feature of preclinical Huntington's disease (HD) but the underlying changes in the HD brain contributing to the development of depression are unknown. Using the R6/1 transgenic mouse model of HD, we show that pre-motor symptomatic HD mice display sex-specific depressive-related behaviors on the forced-swim (FST), tail-suspension (TST) and novelty-suppressed feeding (NSFT) tests while having muted responses to acute anti-depressant administration. The baseline behaviors of HD mice were similar to the behavioral phenotypes of serotonin (5-HT) receptor and transporter null mutants, and gene expression of specific serotonin receptors were subsequently found to be reduced in the hippocampus and cortex of HD mice. Female HD mice had an additional deficit in cortical expression of serotonin transporter (SerT). Environmental enrichment normalized the FST behavioral response of female HD mice corresponding with increased gene expression of specific 5-HT receptors in the hippocampus and cortex. Our findings implicate altered serotonergic signaling as the basis for the development of depression during the preclinical stages of HD.
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PMID:Altered serotonin receptor expression is associated with depression-related behavior in the R6/1 transgenic mouse model of Huntington's disease. 1900 1

Dysfunction of the hypothalamic-pituitary-adrenal axis resulting in elevated baseline glucocorticoid concentrations is a hallmark of stress-related human anxiety and affective disorders, including depression. Mice from four replicate lines bred for high voluntary wheel running (HR lines) run almost three times as much as four non-selected control (C) lines, and exhibit two fold elevated baseline circulating corticosterone levels throughout the 24 h cycle. Although elevated baseline CORT may be beneficial for high locomotor activity, chronic elevations can have deleterious effects on multiple systems, and may predispose for affective disorders. Because stressful events often precede a depressive bout, we quantified depressive-like behavior in the forced-swim (FST; generation 41) and tail-suspension tests (TST; generation 47) in HR and C mice that had wheel access for 6 days and then were deprived of wheels on day seven prior to the FST or TST. Male HR spent significantly more time immobile in the FST than C, suggesting that HR males have a predisposition for depression-like behavior. Both male and female HR (generation 43) were more active than same-sex controls in both wheel running and home-cage activity across 22 h (pooling the sexes, HR/C = 2.28 and 2.66, respectively).
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PMID:Behavioral despair and home-cage activity in mice with chronically elevated baseline corticosterone concentrations. 1906 54

Misediting of the serotonin (5HT) 2C receptor (5HT(2C)R) has been implicated in both depression and anxiety. The adenosine deaminases that act on double stranded RNAs (ADARs) are reported to modify the 5HT(2C)R by RNA editing. Transgenic mice misexpressing the RNA editing enzyme ADAR2 show an adult onset obese phenotype due to chronic hyperphagia, but little more than this is known about the behavior of these animals. The present experiments examined whether affect-associated behaviors are also altered in ADAR2 transgenic mice. Age- and weight-matched transgenic mice misexpressing ADAR2 were tested for signs of behavioral despair with the forced swim (FST) and tail suspension (TST) tests, and for anxiety by evaluating spontaneous exploration in a novel environment and by elevated plus maze performance. Plasma corticosterone was also determined by radioimmunoassay. Transgenic mice of both sexes displayed indications of increased behavioral despair on first exposures to the TST and the FST. Behavioral despair persisted in ADAR2 mice in that it was also observed in the FST in tests administered 24 h and 1 week following the initial TST and FST. ADAR2 transgenic mice also displayed behaviors associated with anxiety as indicated by decreased entry into the open arms in an elevated plus maze test. Both sexes of ADAR2 transgenic mice displayed elevated plasma corticosterone. Taken together, the results suggest that ADAR2 transgenic mice represent a novel rodent model of endogenous behavioral despair and anxiety accompanied by elevated hypothalamo-pituitary adrenal axis activity.
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PMID:Affect-related behaviors in mice misexpressing the RNA editing enzyme ADAR2. 1936 36

The widely reported effects of oxytocin (OT) on CNS function has generated considerable interest in the therapeutic potential for targeting this system for a variety of human psychiatric diseases, including anxiety disorders, autism, schizophrenia, and depression. The utility of synthetic OT, as both a research tool and neurotherapeutic, is limited by the physiochemical properties inherent in most neuropeptides, notably its short half-life and poor blood brain barrier penetration. Subsequently, the discovery and development of non-peptide molecules that act as selective agonists of the oxytocin receptor (OTR) has been an important goal of the field. In this study, we report the receptor and behavioral pharmacology of WAY-267464, a first generation small-molecule OTR agonist. WAY-267464 is a high-affinity, potent, and selective (vs. V1a, V2, V1b) agonist of the OTR. In assays measuring both behavioral (four-plate test, elevated zero maze) and autonomic (stress-induced hyperthermia) parameters of the anxiety response, WAY-267464 exhibits an anxiolytic-like profile similar to OT. We have demonstrated that the anxiolytic-like profile of WAY-267464 is mediated through central sites of action. WAY-267464 also significantly reverses disruption in prepulse inhibition of the acoustic startle reflex induced by either MK-801 or amphetamine, similar to the antipsychotic-like effects previously reported for OT. Interestingly, in the mouse tail suspension test, WAY-267464 failed to produce changes in immobility that are seen with OT, raising the question of whether the antidepressant-like activity of OT may be working independently of the OTR. A selective OTR antagonist also failed to block the effects of OT on immobility in the TST. The significance of these findings for shaping the clinical development of OTR agonists is discussed.
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PMID:Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin receptor agonist. 1961 87

The present study investigated antidepressant-like interaction of five herb polysaccharide fractions from Banxia-Houpu decoction, composed of rhizome pinelliae (PRP), magnolia bark (PMB), poria (PPO), ginger rhizome (PGR) and folium perillae (PFP) by a L(16)(2(5)) orthogonal array design with a two-factor interaction in the tail suspension and forced swimming and tests (TST, FST) in mice. Serotonin (5-HT) and dopamine (DA) levels in whole mouse brain were simultaneously examined after the FST exposure. Polysaccharides PMB, PPO, PFP, and interactions of PRP x PGR, PMB x PFP, PPO x PFP reduced immobility in the mouse FST. Furthermore, PMB and PPO were two principal components of polysaccharides elevating brain 5-HT levels. PFP was an adjuvant component elevating brain DA levels. These results demonstrated that ineffective PRP exhibited antidepressant-like effects when combined with another ineffective PGR, and PFP played a role in assisting effects of PMB and PPO. Therefore, PMB x PFP and PPO x PFP interactions on antidepressant-like effects were the cores in compatibility of polysaccharides from Banxia-Houpu decoction by attenuating abnormalities in the serotonergic and dopaminergic system functions in animal models of depression.
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PMID:Orthogonal array design for antidepressant compatibility of polysaccharides from Banxia-Houpu decoction, a traditional Chinese herb prescription in the mouse models of depression. 1989 5

Radix Polygalae ("Yuan Zhi", the roots of Polygala tenuifolia Willd., YZ) is an important herb used in traditional Chinese medicine to mediate depression. The present study was designed to verify the antidepressant effects of the standardized YZ ethanol extract (YZE) and its four fractions YZ-30, YZ-50, YZ-70 and YZ-90 on the tail suspension (TST) and forced swimming test (FST). Furthermore, the standardization of the fractions obtained from the separation procedures was carried out by high-performance liquid chromatography (HPLC)-fingerprint. The YZ-50 fraction (Oligosaccharide esters--enriched, oral (200 mg/kg) showed a significant anti-immobility like effects. The data of YZ-50 on the corticosterone-induced injure of SH-SY5Y human neuroblastoma cell indicated that YZ-50 may have biological effects on neuroprotection. Proliferation of cell lines was assessed by dimethylthiazoldiphenyltetrazoliumbromide (MTT) and 5-bromo-2'-deoxyuridine (BrdU) incorporation assays. It was found that YZ-50 and its two bioactive compounds, 3,6'-di-o-sinapoyl-sucrose (DISS) and tenuifoliside A(TEA) showed protection activities in SY5Y cells from the lesion. By using bioassay-screening methods, our results indicate that the presence of oligosaccharide esters such as DISS and TEA in this herb may be responsible for the cytoprotective activity effects.
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PMID:Potential antidepressant properties of Radix Polygalae (Yuan Zhi). 2054 23

During last decades abnormalities of neuro-psychic sphere have become a topic of great interest. Among them an important place takes depression. Psychogenic factors are commonly the most frequent cause of depressive condition, and till now the study of so-called transitional period (from the beginning of stressor action till the formation of depressive state) continues to be an actual task of scientific research. Minding this, we studied the self-regulating behavior in rats in different stages of psychogenic stress till the formation of depression-like condition. To access the behavioral changes, the "open field" test, FST (forced swimming test, "Porsolt" test) and TST (tail suspension test) were used. We also registered behavioral indices while applying stressors. Stress was applied in a modified shuttle chamber. At the very beginning of the study (the first stage of stress-alarm) an animal was forced to develop a reaction of active avoidance on metronome beats (100 beats per second), later, after its fixation, the same reaction was developed on tone (500 Hz). Then simultaneous testing of two developed reactions of active avoidance was performed (the second stage of stress). After the long-term application of stressors (48 days) the second stage of stress proceeds into the deep (the third) one. On this stage animals showed decreased motor activity in the "open field" test, decreased mobility in FST and TST, changes being statistically valid. All behavioral changes indicating depression-like condition in the animals were normalized after per os administration of antidepressant Fluoxetine at doses of 40 mg/kg. The results obtained in the study confirm that on different stages of psychogenic stress changes in behavioral indices are natural and self-regulating. They appear to be compensatory as only on their exhaustion the depression-like condition is formed.
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PMID:[Study of self-regulating behavior at different stages of psychogenic stress before the formation of depressive-like state in rats]. 2143 79

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