UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of drugs from diverse pharmacological classes are in use for migraine prevention. Traditionally, they have been discovered by serendipity. Examples include beta-adrenergic blockers, anticonvulsants, tricyclic antidepressants, and serotonin receptor antagonists. The mechanisms of action of migraine preventive drugs are multiple but it is postulated that they converge on two targets: (1) inhibition of cortical excitation; (2) restoring nociceptive dysmodulation. The antiepileptic drugs (e.g., topiramate, valproate, gabapentin), calcium channel blockers such as verapamil, and inhibitors of cortical spreading depression are some examples of drugs that reduce neuronal hyperexcitability. On the other hand, modulators of the serotonergic and adrenergic systems and cholinergic enhancing drugs may restore descending nociceptive inhibition and play a role in migraine prevention. To date, Level 1 evidence and clinical experience favor the use of the antidepressant amitriptyline, the anticonvulsants divalproex and topiramate, and the beta-adrenergic blockers propranolol, timolol and metoprolol as first line migraine preventive drugs. The evidence for others (e.g., verapamil) is not as strong. Migraine preventive drugs have varying degrees of adverse effects, some of which could be limiting, and their efficacy should balanced with their risks of adverse effects, patients' expectations and desires, and compliance. It is hoped that future migraine preventive drugs target migraine mechanisms more specifically, which could well enhance the therapeutic index.
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PMID:Current trends in migraine prophylaxis. 1742 10

To clarify nosologic differences between schizoaffective psychosis (SAP) and attack-like progressive schizophrenia at molecular-genetic level, the genetic polymorphism of serotonin receptor type 2A (5HTR2A), serotonin transporter (5-HTTLRP), and brain-derived neurotrophic factor (BDNF) was studied in 563 patients with schizophrenia (mean age 37.7+/-14.4 years, age at disease onset 26.7+/-11.4 years), and 171 patients with SAP (mean age 30.7+/-11.6 years, age at disease onset 24.9+/-8.5 years). The control group consisted of 536 psychiatrically well subjects. Clinical symptoms and personal features were evaluated as well. By comparison with schizophrenic patients, those with SAP were featured by subtle negative symptoms and personality changes that supported the evidence that SAP is a disorder with a favorable outcome. Molecular-genetic studies revealed higher frequencies of S allele and SS genotype (5-HTTLPR polymorphism), which are thought to be associated with depression and depressive symptoms, and higher frequency of BDNF genotypes, containing Met allele, in combination with 5-HTTLRP genotypes containing L allele, in patients with SAP as compared to the schizophrenic group. C allele and CC genotype (T102C 5-HTR2A polymorphism) frequencies were higher in both groups of patients vs. controls. In conclusion, the results confirm the concept considering SAP an independent nosologic category.
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PMID:[The molecular-genetic aspects of differentiation of schizoaffective psychosis and attack-like progressive schizophrenia]. 1750 Feb 7

Depression is the most frequent and costly problem in primary care, where most of these patients are seen and treated. In many countries, the public regard antidepressant drugs as 'addictive', partly because of the withdrawal symptoms that can occur when they are discontinued. Indeed, discontinuation (withdrawal) symptoms can follow the stoppage of almost all classes of antidepressants, including selective serotonin receptor inhibitors (SSRIs). This is important because they are widely regarded as drugs of choice for both depression and the anxiety disorders. But is this true withdrawal or merely rebound? The antidepressant discontinuation syndrome is characterised by the time-locked emergence of new, clearly defined and quantifiable signs and symptoms that ensue on stopping or reducing the dose of an antidepressant. Thereby, it meets the criteria for a withdrawal syndrome. The symptoms are not usually severe or protracted. SSRIs vary in their propensity to be associated with a discontinuation syndrome: paroxetine appears to be the most likely. Patients should be warned of the possibility of developing such a reaction, but reassured that it is usually mild and self limiting. Tapering the dose, if practicable, is worthwhile. In severe cases, temporary reinstatement of the SSRI and slower tapering may be necessary. Escalation of antidepressant dosage, or 'street abuse', is rare with antidepressants. The use of antidepressants is generally beneficial, and efforts should be made to optimise our current use of these drugs as well as encouraging the development of newer, better and innovative compounds. To this end, physicians should educate themselves and the public about discontinuation and withdrawal, so that these clinical features can be put in a realistic context.
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PMID:Pharmacotherapy of mood disorders and treatment discontinuation. 1768 67

In recent years several arylpiperazine derivatives have reached the stage of clinical application, mainly for the treatment of depression, psychosis or anxiety. Examples are the pyrimidinylpiperazine buspirone, the chlorophenylpiperazine derivatives nefazodone and trazodone, the dichlorophenylpiperazine aripiprazole and the benzisothiazolyl derivatives perospirone and ziprasidone. Most of them undergo extensive pre-systemic and systemic metabolism including CYP3A4-dependent N-dealkylation to 1-aryl-piperazines. These metabolites are best known for the variety of serotonin receptor-related effects they cause in man and animals, although some have affinity for other neurotransmitter receptors; others, however, are still largely unexplored despite uncontrolled use as amphetamine-like designer drugs. Once formed they distribute extensively in tissues, including brain which is the target site of most arylpiperazine derivatives, and are then primarily biotransformed by CYP2D6-dependent oxidation to hydroxylates which are excreted as conjugates; only 1-(2-benzisothiazolyl)-piperazine is more susceptible to sulfur oxidation than to aromatic hydroxylation. In studies analysing animal brain and human blood, 1-aryl-piperazine concentrations were either higher or lower than the parent compound(s), although information is available only for some derivatives. At steady state, the metabolite-to-parent drug ratios varied widely among individuals taking the same dosage of the same arylpiperazine derivative. This is consistent with the known individual variability in the expression and activity of CYP3A4 and CYP2D6. This review also surveys current published information on physiological and pathological factors affecting the 1-aryl-piperazine-to-parent drug ratios and examines the potential role of 1-aryl-piperazine formation in the pharmacological actions of the arylpiperazine derivatives that are already or will shortly be available in major markets.
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PMID:N-dealkylation of arylpiperazine derivatives: disposition and metabolism of the 1-aryl-piperazines formed. 1769 20

Suicidal behavior is highly correlated with many emotional disturbances and some psychiatric disorders. The biogenic amine, serotonin, is one of the most important neurotransmitter in the central nervous system believed to play a huge role in pathogenesis of some kind of mental disorders. Drugs targeting serotonin receptors like serotonin reuptake inhibitors (SSRIs) are useful in the present therapy of anxiety and depression. Recent studies have reported that genetic factors are associated with development of some psychiatric disorders. Serotonin receptor single nucleotide polymorphism (SNP) has emerged as the subject of controversial result in correlation with suicide attempt. Further studies should be performed to confirm the influence of allelic variation of serotonin receptor on elevated risk of auto-aggression behavior. The aim of our study was to examine the frequency and genotype distribution of C(-1019)G polymorphism of regulatory region 5-HT1A receptor in the group of 65 suicide attempters and 63 persons in the control group. Using allele specific amplification PCR (ASA-PCR), we found that allele G was higher in suicidal attempters. The genotype frequency was significantly different between hospitalized patients and control subjects. The most common intoxication causes were antidepressants (56.9%), analgesics (18.5%) and cardiologic drugs (10.8%). Our data support hypothesis which indicate role of the 5-HT1A C(-1019)G SNP polymorphism in elevated risk of suicidal attempt.
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PMID:Association between 5-hydroxytryptamine 1A receptor gene polymorphism and suicidal behavior. 1772 68

Frequently disrupted and restricted sleep is a common problem for many people in our modern around-the-clock society. In this context, it is an important question how sleep loss affects the stress systems in our bodies since these systems enable us to deal with everyday challenges. Altered activity and reactivity of these systems following insufficient sleep might have serious repercussions for health and well-being. Studies on both humans and rodents have shown that sleep deprivation and sleep restriction are conditions often associated with mild, temporary increases in the activity of the major neuroendocrine stress systems, i.e., the autonomic sympatho-adrenal system and the hypothalamic-pituitary-adrenal axis. Sleep deprivation may not only have a direct activating effect by itself but, in the long run, it may also affect the reactivity of these systems to other stressors and challenges. Although the first signs of alterations in the way people deal with challenges under conditions of restricted sleep appear to be on the level of emotional perception, chronic sleep restriction may ultimately change the fundamental properties of neuroendocrine stress systems as well. Understandably, few controlled studies in humans have been devoted to this topic. Yet, experimental studies in rodents show that chronic sleep restriction may gradually alter neuroendocrine stress responses as well as the central mechanisms involved in the regulation of these responses. Importantly, the available data from studies in laboratory animals suggest that sleep restriction may gradually change certain brain systems and neuroendocrine systems in a manner that is similar to what is seen in stress-related disorders such as depression (e.g., reduced serotonin receptor sensitivity and altered regulation of the hypothalamic-pituitary-adrenal axis). Such data support the view that insufficient sleep, by acting on stress systems, may sensitize individuals to stress-related disorders. Indeed, epidemiological studies suggest that sleep complaints and sleep restriction may be important risk factors for a variety of diseases that are often linked to stress, including cardiovascular diseases and mood disorders.
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PMID:Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity. 1822 99

In DSM-IV the occurrence of disturbed sleep is one of the principal diagnostic criteria for major depressive disorder (MDD). Further, there is evidence of reciprocity between the two conditions such that, even in the absence of current depressive symptoms, disturbed sleep often predicts their development. The present review discusses the effects of antidepressants on sleep and evaluates the use of the recently developed melatonin agonist-selective serotonin antagonists on sleep and depression. Although many antidepressants such as the tricyclics, monoamine oxidase inhibitors, serotonin-norepinephrine reuptake inhibitors, several serotonin receptor antagonists and selective serotonin reuptake inhibitors (SSRIs) have all been found successful in treating depression, their use is often associated with a disruptive effect on sleep. SSRIs, currently the most widely prescribed of the antidepressants, are well known for their instigation or exacerbation of insomnia. The recently introduced novel melatonin agonist and selective serotonin antagonist antidepressant, agomelatine, which has melatonin MT(1) and MT(2) receptor agonist and 5-HT(2c) antagonist properties, has been useful in treating patients with MDD. Its rapid onset of action and effectiveness in improving the mood of depressed patients has been attributed to its ability to improve sleep quality. These properties underline the use of melatonin analogues as a promising alternative for the treatment of depression.
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PMID:The effect of melatonergic and non-melatonergic antidepressants on sleep: weighing the alternatives. 1860 22

17beta-estradiol has been reported to possess antidepressant-like activity in animal models of depression, although the mechanism for its effect is not well understood. The present study is an effort in this direction to explore the mechanism of the antidepressant-like effect of 17beta-estradiol in a mouse model(s) of behavioral depression (despair behavior). Despair behavior, expressed as helplessness to escape from a situation (immobility period), as in a forced swim test in which the animals are forced to swim for a total of 6 min, was recorded. The antiimmobility effects (antidepressant-like) of 17beta-estradiol were compared with those of standard drugs like venlafaxine (16 mg/kg, i.p.). 17beta-estradiol produced a U-shaped effect in decreasing the immobility period. It had no effect on locomotor activity of the animal. The antidepressant-like effect was comparable to that of venlafaxine (16 mg/kg, i.p.). 17beta-estradiol also exhibited a similar profile of antidepressant action in the tail suspension test. When coadministered with other antidepressant drugs, 17beta-estradiol (5 microg/kg, i.p.) potentiated the antiimmobility effect of subeffective doses of fluoxetine (5 mg/kg, i.p.), venlafaxine (2 mg/kg, i.p.), or bupropion (10 mg/kg, i.p.), but not of desipramine (5 mg/kg, i.p.) or tranylcypromine (2 mg/kg, i.p.), in the forced swim test. The reduction in the immobility period elicited by 17beta-estradiol (20 microg/kg, i.p.) was reversed by haloperidol (0.5 mg/kg, i.p.; a D(2) dopamine receptor antagonist), SCH 23390 (0.5 mg/kg, i.p.; a D(1) dopamine receptor antagonist), and sulpiride (5 mg/kg, i.p.; a specific dopamine D(2) receptor antagonist). In mice pretreated with (+)-pentazocine (2.5 mg/kg, i.p.; a high-affinity sigma-1 receptor agonist), 17beta-estradiol (5 microg/kg, i.p.) produced a synergistic effect. In contrast, pretreatment with progesterone (10 mg/kg, s.c.; a sigma-1 receptor antagonist neurosteroid), rimcazole (5 mg/kg, i.p.; another sigma-1 receptor antagonist), or BD 1047 (1 mg/kg, i.p.; a novel sigma-1 receptor antagonist) reversed the antiimmobility effects of 17beta-estradiol (20 microg/kg, i.p.). Similarly, in mice pretreated with a subthreshold dose of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A serotonin receptor agonist), 17beta-estradiol (5 microg/kg, i.p.) produced an antidepressant-like effect. These findings demonstrate that 17beta-estradiol exerted an antidepressant-like effect preferentially through the modulation of dopaminergic and serotonergic receptors. This action may also involve the participation of sigma-1 receptors.
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PMID:Antidepressant-like effect of 17beta-estradiol: involvement of dopaminergic, serotonergic, and (or) sigma-1 receptor systems. 1884 Nov 77

We examine the interaction between stressful life events (SLE) and genotypes for the length polymorphism of the serotonin receptor gene (5HTTLPR) on risk of depression. We hypothesize that if the interaction is real, monozygotic twin pairs (MZT) homozygous for the short allele (SS) will have a greater within pair variance in depression measures than MZT homozygous for the long allele (LL), as a reflection of their increased sensitivity to unknown environmental risk factors. Telephone interviews were used to assess symptoms of depression and suicidality on 824 MZT. Rather than using the interview items to calculate sum scores or allocate diagnostic classes we use Item Response Theory to model the contribution of each item to each individual's underlying liability to depression. SLE were also measured on the MZT assessed by mailed questionnaire on average 3.8 years previously, and these were used in follow-up analyses. We find no evidence for significant differences in within pair variance between 5HTTLPR genotypic classes and so can provide no support for interaction between these genotypes and the environment. The use of MZT provides a novel framework for examining genotype x environment interaction in the absence of measures on SLE.
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PMID:Use of monozygotic twins to investigate the relationship between 5HTTLPR genotype, depression and stressful life events: an application of Item Response Theory. 1897 45

Thyroxine synthesis inhibitors increase the predisposition to catalepsy and decrease sexual motivation and the amplitude of the acoustic startle reflex in rats. The sensitivity of these behavioral changes to antidepressants remains uncertain. Chronic administration of the classical tricyclic antidepressant imipramine (15 mg/kg, 21 days) prevented the appearance of high sensitivity to catalepsy and the decrease in sexual motivation in Wistar rats given propylthiouracil (50 mg/liter, 28 days), without altering the amplitude of the startle reflex. Normalization of behavior in response to imipramine was not associated with changes in movement activity in the open field test or the animals' body weight. There was also no change in the expression of the 5-HT2A serotonin receptor gene in the frontal cortex. The model of propylthiouracilinduced catalepsy with reduced sexual motivation in rats has potential for studying the role of thyroid abnormalities in the development of depression and the mechanisms of action of antidepressants.
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PMID:Chronic administration of imipramine normalizes decreased sexual motivation and increased predisposition to catalepsy induced by propylthiouracil in rats. 1934 May 85

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