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

Fibromyalgia syndrome [FM] has core clinical features of widespread pain and widespread abnormal tenderness. The specific cause of the altered neurophysiology that underpins these clinical manifestations remains unclear. However, increased sensitisation of neural networks that relates to pain, as well as interacting mechanoreceptors, appear important targets for modulation by pharmacological agents. Further, many FM patients have emotional distress and some are depressed. Antidepressant agents have therapeutic benefits in FM. If depression is present antidepressant drugs will provide typical benefits to mood but not always to other key outcome measures, such as pain or tenderness. Selective serotonin receptor reuptake blockers are not as effective for overall FM improvement as drugs that block both serotonin and norepinephrine in a relatively balanced way. Thus tricyclic antidepressants will improve many important FM outcomes but are effective in only about 40 percent of individuals. Newer agents of this class, such as duloxetine and milnacipran, show improvement in key FM outcomes in about 60 percent of patients. Longer term studies will indicate the durability of these responses and the overall tolerance of the drugs. Any drug therapy will need to be integrated with appropriate education, exercise and attention to psychological modulatory factors to achieve best results.
 ...
PMID:Fibromyalgia syndrome: which antidepressant drug should we choose. 1645 18

The monoamine theory is one of the major hypotheses about the biological etiology of major depressive disorders. Recent pharmacological and postmortem investigations suggest that depressed patients have alterations in function of serotonergic neuronal system. However, the exact sites of alterations and the association between these alterations and the etiology of the disorder are still unclear. To elucidate these issues, we immunohistochemically examined vesicle monoamine transporter 2 (VMAT2), serotonin receptor type 1a (5HT1a), and serotonin transporter (5HTT) in the hippocampal region of reserpine-treated rats, an animal model of depression. The results showed more VMAT2-immunoreactive varicose fibers in the pyramidal cell layer of hippocampus and parahippocampal cortexes, and more intense 5HTT-immunoreactivity in the pyramidal cell layer and the area CA4 of hippocampus in the animal models compared to those of the controls. On the other hand, lower density of 5HT1a-immunoreactive deposits in the pyramidal cell layer of hippocampus and the parahippocampal cortex was observed in the animal models compared to those of the controls. These results suggest that a deficit of monoamines induces the alterations in the expression of the storage protein, the receptor and the transporter that are involved in the serotonergic neurotransmission in the hippocampal region. These alterations may underlie the changes of serotonergic system observed in the brains of patients with the depressive disorder.
 ...
PMID:Immunohistochemical study of the serotonergic neuronal system in an animal model of the mood disorder. 1667 34

Antidepressant drugs represent the principal form of treatment for major depressive disorder. While there are a plethora of medications available for this task, current drugs have many shortcomings. In the face of these deficiencies there is an ongoing search for new agents. The search has been guided, in part, by drug design based on existing agents and their putative mechanism of action. This has been less than fruitful in addressing inadequacies of existing medications as it has not produced compounds which are novel in terms of pharmacological mechanisms. Recent insights from molecular biological approaches hold promise for the discovery of novel compounds, in particular the so-called neurogenesis hypothesis suggests novel therapeutic approaches. Although significantly modified over the years, the monoamine hypothesis of depression and antidepressant drug action still remains an important driving force behind the development of new compounds. Several recently marketed agents and some in early-phase development tend to conform to these existing mechanistic hypotheses. Clearly the place of these agents in the treatment of depression is dependent on issues such as short- and long-term safety and efficacy. Duloxetine has been developed as a dual monoamine re-uptake inhibitor. Agomelatine is a compound with major effects on the circadian system as well as effects on subtypes of the serotonin receptor system. While the mechanism of action of this compound is not certain, recent evidence would suggest that the drug exerts its effects through antagonist actions at serotonin receptors. Compounds based on the hypothalamic pituitary adrenal axis, substance P antagonism and other neuropeptides have potential application for the treatment of depression but require further development before that potential is realized.
 ...
PMID:Prospects for the treatment of depression. 1668 61

Since the 1950s, when serotonin (5-HT) was discovered in the mammalian central nervous system (CNS), an enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a number of cognitive and behavioural functions. Although 5-HT is synthesized by a small group of neurons within the raphe nuclei of the brain stem, almost all parts of the CNS receive serotonergic projections. Furthermore, the importance of 5-HT modulation and the fine-tuning of its action is underlined by the large number of 5-HT binding sites found in the CNS. Hitherto, up to 15 different 5-HT receptors subtypes have been identified. This review was undertaken to summarize the work that has explored the pathophysiological role of one of these receptors, the 5-HT2C receptor, that has been emerged as a prominent central serotonin receptor subtype. The physiology, pharmacology and anatomical distribution of the 5-HT2C receptors in the CNS will be firstly reviewed. Finally, their potential involvement in the pathophysiology of depression, schizophrenia, Parkinson's disease and drug abuse will be also discussed.
 ...
PMID:Central serotonin2C receptor: from physiology to pathology. 1701 66

Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric phenotypes influenced by both genetic and environmental factors. We investigated the genetic contribution of four single nucleotide polymorphisms (SNPs) within the serotonin receptor 5HT2C and two sequence variants within the serotonin transporter SLC6A4 to different ED-related psychopathological symptoms in a total sample of 82 ED patients. All patients were diagnosed according to DSM-IV criteria and underwent diagnostic and psychopathological assessments by means of structured clinical interviews and rating scales. We detected significant evidence of association between the -995A/-759T/-697C/Cys23 haplotype of the 5HT2C gene and different anxious and depressive subscales of the SCL90-R instrument, that included Somatization (p = 0.029), Obsessive-Compulsiveness (p = 0.021), Depression (p = 0.032), Anxiety (p = 0.004), Hostility (p = 0.028), Phobic Anxiety (p = 0.029) and Paranoid Ideation (p = 0.008), in BN patients. We also observed a strong association between the 5HTTLPR polymorphism of the SLC6A4 gene and Anxiety in the same group of BN patients (p = 0.004). However, no epistatic effects between the 5HT2C and SLC6A4 genes on the different anxious and depressive subscales were observed. Our preliminary data suggest that the serotoninergic system contributes to the different psychopathological symptoms that may be partially responsible for the phenotypical variability within the bulimic phenotype.
 ...
PMID:Contribution of the serotoninergic system to anxious and depressive traits that may be partially responsible for the phenotypical variability of bulimia nervosa. 1705 31

The Neuropsychiatric Inventory (NPI) was introduced in 1994 and has since become a standard instrument for clinical trials and other types of behavioral research in dementing disorders. Its reliability and validity have been confirmed. The NPI was the subject of a workshop in Asia in conjunction with the International Workgroup on Dementia Drug Guidelines (IWG). Investigators using the NPI from 4 Asian areas--Taiwan, Hong Kong, Japan, Thailand--presented conclusions from their research. A high prevalence of behavioral disturbances across Asian countries was found and the rates are similar to those observed in Western countries. Apathy is more difficult to detect and characterize in Asian populations. Neurobiologic studies show an excess of some serotonin receptor gene polymorphisms in patients without behavioral disturbances and positron emission tomography reveals reductions in frontal lobe metabolism in patients manifesting depression as measured by the NPI. Studies in Thailand show relationships among verbal fluency, activities of daily living, and neuropsychiatric symptoms particularly agitation, apathy, and disinhibition. This suggests a triad of symptoms of behavioral abnormalities, executive dysfunction, and abnormalities of activities of daily living that impugn frontal lobe function. The NPI is a reliable and useful instrument to characterize behavioral changes in Asian and Western populations.
 ...
PMID:Neuropsychiatric inventory workshop: behavioral and psychologic symptoms of dementia in Asia. 1713 81

Patients with Alzheimer disease (AD) often exhibit psychiatric symptoms associated with cognitive impairment. The serotoninergic system may be involved in the development of depressive symptoms in AD patients, as suggested by the evidence that antidepressant drugs having the serotonin transporter as their target are effectively used to treat depressive AD patients. The aim of this study was to investigate the role of serotonin in depression, searching for association of two serotoninergic polymorphisms (T102C of serotonin receptor 5-HT2A and serotonin transporter linked polymorphic region -5-HTTLPR- of SLC6A4 gene) with depressive symptoms and considering their possible interactions with Apolipoprotein E (ApoE) and between themselves, in a sample of 208 sporadic AD patients and 116 normal controls from Italy. 5-HTTLPR and T102C are not associated with AD when separately analysed. However, we found out an interaction between the two polymorphisms in L/L and C/C genotype carriers increasing the risk for the disease (p=0.015, OR=8.048; 95% CI: 1.497-43.262). No association of the polymorphisms was detected with depression linked to AD. No interaction between 5-HTTLPR and T102C was detected in depressive AD subjects, even after stratification according to the presence of ApoE4 allele. These results suggest that the serotoninergic system may be not involved in the pathogenesis of depressive symptoms in AD patients, and it may be involved in other aspects of disease pathophysiology like cognitive symptoms and psychosis.
 ...
PMID:No evidence for allelic association of serotonin 2A receptor and transporter gene polymorphisms with depression in Alzheimer disease. 1718 48

Based on experiments in rats, serotonin receptor 5-hydroxytryptamine (5-HT)(1A) agonists have been proposed as a potential therapeutic strategy for the selective treatment of opioid-induced respiratory depression. We investigated the clinical applicability of this principle in healthy volunteers. Twelve subjects received 0.43 mg/kg morphine (30 mg for 70 kg body weight) administered intravenously (i.v.) over approximately 2 h. At the start of the morphine infusion, they received in a randomized, double-blind cross-over design 60 mg p.o. buspirone or placebo. Respiratory depression (hypercapnic challenge) and pain (electrical stimuli: 5 Hz sinus 0-20 mA; chemical stimuli: 200 ms gaseous CO(2) pulses applied to the nasal mucosa) were assessed at baseline, at the end of the morphine infusion, and a third time after antagonizing the opioid effects by i.v. administration of 2 mg naloxone. The linear relationship between the minute ventilation and the CO(2) concentration in the inspired air of 1.07+/-0.27 l/mm Hg CO(2) at baseline conditions became shallower (0.45+/-0.23 l/mm Hg CO(2)) after morphine administration (P<0.001), indicating respiratory depression, which was significantly reversed by naloxone (0.95+/-0.43 l/mm Hg CO(2); P=0.001). Co-administration of buspirone had no effect on morphine-induced respiratory depression (slope 0.45+/-0.23 l/mm Hg CO(2) under morphine plus placebo versus 0.38+/-0.25 l/mm Hg CO(2) under morphine plus buspirone; P=0.7). Significant morphine-induced analgesia was observed in both pain models and was reversed by naloxone but unaffected by buspirone. Buspirone significantly increased the nausea induced by morphine (P=0.011). Oral co-administration of a high dose of the clinically available 5-HT(1A) agonist buspirone cannot be advised as a remedy for opioid-induced respiratory depression. This is indicated by its lack of anti-respiratory depressive effects and by the buspirone-associated increase of morphine-induced nausea.
 ...
PMID:The partial 5-hydroxytryptamine1A receptor agonist buspirone does not antagonize morphine-induced respiratory depression in humans. 1718

Depression is the most common psychiatric comorbidity in epilepsy. To better understand the contribution of seizures versus environment to depression in epilepsy, we investigated differential gene expression using microarray and quantitative RT-PCR, and depressive behavior, in the Porsolt forced swim test in juvenile rats reared in different environments after kainic acid (KA)-induced seizures. We selected for genes significantly down-regulated by KA seizures and upregulated by environmental enrichment. This common gene selection process yielded one known gene involved in mood and affect: serotonin receptor 5B. The changes in serotonin receptor gene expression were paralleled by decreased mobility in the forced swim tests; depressive behavior exhibited after seizures was no longer evident in rats reared in environmental enrichment. Our results suggest that seizures lead to increased susceptibility to depression through transcriptional regulation while environment, in turn, can interact with gene expression to influence the behavioral outcome of epilepsy.
 ...
PMID:Depressive behavior and selective down-regulation of serotonin receptor expression after early-life seizures: reversal by environmental enrichment. 1719 83

Although numerous stress-related molecules have been implicated in vulnerability to psychiatric illness, especially major depression and anxiety disorders, the role of the brain mineralocorticoid receptor (MR) in stress, depression, and affective function is not well defined. MR is a steroid hormone receptor that detects circulating glucocorticoids with high affinity and has been primarily implicated in controlling their basal level and circadian rhythm. To specifically address the role of MR in hypothalamic-pituitary-adrenal axis activity and anxiety-related behaviors, we generated transgenic mice with increased levels of MR in the forebrain (MRov mice) by using the forebrain-specific calcium/calmodulin-dependent protein kinase II alpha promoter to direct expression of MR cDNA. A mild but chronic elevation in forebrain MR results in decreased anxiety-like behavior in both male and female transgenic mice. Female MRov mice also exhibit a moderate suppression of the corticosterone response to restraint stress. Increased forebrain MR expression alters the expression of two genes associated with stress and anxiety, leading to a decrease in the hippocampal glucocorticoid receptor (GR) and an increase in serotonin receptor 5HT-1a, consistent with the decreased anxiety phenotype. These data suggest that the functions of forebrain MR may overlap with GR in hypothalamic-pituitary-adrenal axis regulation, but they dissociate significantly from GR in the modulation of affective responses, with GR overexpression increasing anxiety-like behavior and MR overexpression dampening it. These findings point to the importance of the MR:GR ratio in the control of emotional reactivity.
 ...
PMID:Mineralocorticoid receptor overexpression in forebrain decreases anxiety-like behavior and alters the stress response in mice. 1736 May 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>