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)

Rats were given a single dose of reserpine (5 mg/kg s.c.) and behavioural responses to agonists at 5-HT receptor subtypes compared with those of control animals 21 days later. The following effects of activating postsynaptic 5-HT1A receptors by the agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) were significantly increased: tail-flick, reciprocal forepaw treading, flat body posture. The hyperphagic effect of activating presynaptic 5-HT1A receptors by 8-OH-DPAT tended to increase and hypothermia on activating postsynaptic 5-HT1A sites tended to decrease. The hyperlocomotor effect of activating 5-HT1A sites also tended to decrease possibly as a result of a dependence of this response on the known depletion of catecholamines by reserpine. Head shakes on activating 5-HT2A receptors by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and two effects of activating 5-HT2C receptors by 1-(3-chlorophenyl) piperazine (mCPP) were significantly increased (hypophagia, anxiety) and a third effect, hypolocomotion tended to increase but hypophagia on activating postsynaptic 5-HT1B receptors by CP-94, 253 was significantly attenuated. The results are discussed with particular reference to altered 5-HT function in depression.
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PMID:Effect of reserpine on behavioural responses to agonists at 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptor subtypes. 1046 92

Abnormalities of the serotonergic system are involved in the pathophysiology of mood disorders. In the present study, we investigated the possible influence of the T102C polymorphism of the serotonin-2A receptor gene (5-HT2A, 13q14-21) on the symptomatology of mood disorders. Inpatients affected by mood disorders (n = 246, 149 bipolar, 97 major depressive disorder) were assessed with a checklist of operational criteria for psychotic illness (OPCRIT) to score their lifetime psychotic symptomatology. The subjects were also typed for 5-HT2A variants using polymerase chain reaction techniques. No association was found between this polymorphism and psychopathology as defined by the four symptomatologic factors used in phenotype definition (mania, depression, delusion and disorganization). Genetic variation at the 5-HT2A receptor gene does not, therefore, appear to play a major role in the pathogenesis of major mood disorders.
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PMID:No association between serotonin-2A receptor gene polymorphism and psychotic symptomatology of mood disorders. 1048 39

Major depressive disorder (MDD) is a severe psychiatric disorder with a lifetime prevalence of about 15%.1 The importance of the genetic component is well accepted,2 but the mode of inheritance is complex and non-Mendelian. A line of evidence suggests the involvement of serotonin and dopamine neurotransmitters in the pathophysiology of depression. In the present study, 102 unipolar MDD patients and 172 healthy controls were genotyped for polymorphisms in four serotonergic and three dopaminergic candidate genes [tryptophan hydroxylase (TPH), serotonin receptor 2A (HTR2A), serotonin receptor 2C (HTR2C), serotonin transporter promoter region (5-HTTLPR), dopamine receptor D4 (DRD4), dopamine transporter (DAT1) and catechol-O-methyl transferase (COMT)]. There were no statistical differences between MDD patients and healthy controls in the genotypic and allelic distribution of all polymorphisms investigated. Thus, our study does not support a major role for these polymorphisms in contributing to susceptibility to MDD, although it does not preclude minor effects.
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PMID:Association of unipolar major depressive disorder with genes of the serotonergic and dopaminergic pathways. 1048 58

Flibanserin is a 5-HT1A agonist that, in contrast to other 5-HT1A receptor agonists, is capable of activating 5-HT1A receptors in frontal cortex. Flibanserin also behaves as an antagonist at 5-HT2A receptors. This compound has been described to be a putative fast-acting antidepressant owing to these properties. In the present study, the effect of flibanserin was investigated in several behavioral paradigms different from animal models of depression. Intraperitoneal flibanserin, at doses of 4-8 mg/kg, antagonized d-amphetamine- and (+)SKF-10047- induced hypermotility in mice and rats. At doses of 816 mg/kg, flibanserin exerted anxiolytic-like effects in the light/dark exploratory test and stress-induced hyperthermia in mice, and antagonized d-amphetamine- and apomorphine-induced stereotypy in rats. At the dose of 16 mg/kg, flibanserin reduced spontaneous motor activity in rats. At the dose of 32 mg/kg, flibanserin did not exert any clear effect on spontaneous motor activity in mice, or on the elevated plus-maze and the water maze in rats.
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PMID:Behavioral effects of flibanserin (BIMT 17). 1049 8

Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). Correlation of genotypes to clinical parameters revealed no influences on age of onset, duration of disease or psychopathological symptoms, measured with the Beck Depression Inventory and the symptom checklist SCL-90-R. In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann-Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled.
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PMID:The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia. 1052 9

The co-administration of thyroid hormone and antidepressants is often useful in the treatment of refractory depression. The aim of this study is to clarify the anti-depressive mechanisms of repeated co- administration of thyroid hormone (T3) and desipramine (DMI) in the rat brain. Forced swimming test, open-field test, monoamine contents, beta receptor, and serotonin (5HT)2A receptor were compared in four experimental groups (control, T3, DMI, DMI+T3). In the forced swimming test, the (DMI+T3) group showed a significantly decreased immobility time compared with that of the control group. The noradrenaline (NA) content in the prefrontal cortex was highest in the (DMI+T3) group. Although beta receptor was not altered in any brain region in the (DMI+T3) group, 5HT2A receptor was significantly decreased, and the dopamine (DA) turnover rate was significantly increased in the prefrontal cortex. This study suggests that the addition of T3 enhanced the action of DMI alone on the monoaminergic system in the prefrontal cortex.
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PMID:[The influence of L-triiodothyronine on the action of desipramine on beta and serotonin 2A receptor, monoamines in the rat brain]. 1068 Nov 58

The serotonin receptor type 2A (5-HT2A) is a primary candidate for involvement in major psychoses. Polymorphisms within the 5-HT2A gene have recently been reported to be associated with a variety of psychopathological conditions. In the present study, we investigated the potential influence of the T102C polymorphism on the psychopathology of schizophrenia. One hundred eighty-eight inpatients affected by schizophrenia (DSM-III-R) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were typed for their 5-HT2A variants by PCR techniques. Mania, depression, delusion and disorganization were the four symptomatologic factors previously derived from our psychotic population that were used to define phenotype in our sample. Genetic variants of the polymorphism under study were not associated with these symptomatologic factors, and consideration of possible stratification effects such as sex and age of onset did not reveal any association either. Our results do not, therefore, support the hypothesis that the serotonin receptor 2A gene is a liability factor for the symptomatology of schizophrenia as defined by the OPCRIT checklist. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:84-87, 2000.
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PMID:Serotonin-2A receptor gene is not associated with symptomatology of schizophrenia. 1068 58

Platelet serotonin type 2A receptor (5-HT2A) sensitivity changes have previously been documented in depression, although it is unclear if this represents a stable trait marker of the illness, or whether it represents an acute state marker of depression that would change with treatment. Electroconvulsive therapy (ECT) may be a useful intervention to separate out trait and state marker status avoiding the potential confounding effects of pharmacotherapy on receptor function. Using spectrofluorometry, the platelet 5HT2A, receptor sensitivity as reflected by the intracellular calcium response to serotonin stimulation, was measured every week in patients suffering from major depression and undergoing ECT. There was a significant drop in the platelet response to serotonin stimulation over a course of ECT, with an associated progressive decrease in Hamilton Rating Scale of Depression (HAM-D) scores. This may suggest either decreased sensitivity of platelet 5HT2A receptors as a mechanism of action of ECT, or changes in second messengers such as the inositide phospholipid system. This suggests that the enhanced sensitivity of platelet 5HT2A receptors may be a state marker of major depression.
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PMID:Changes in the platelet intracellular calcium response to serotonin in patients with major depression treated with electroconvulsive therapy: state or trait marker status. 1075 40

The available data on the role of 5-HT in a variety of behaviors support the hypothesis that a dysfunction in brain serotoninergic system activity contributes to vulnerability to major depression. The diversity in the electrophysiological actions of 5-HT in the central nervous system can now be categorized according to receptor subtypes and their respective effector mechanisms. In particular, the implication of central postsynaptic 5-HT2A receptor in affective disorders has been supported by findings consistent with the hypothesis of 5-HT2A receptor up-regulation in depression. For these reasons, the 5-HT2A receptor (HTR2A) gene can be considered as a candidate gene in bipolar affective disorder (BPAD). We tested the possible genetic contribution of the polymorphic DNA variation T102C in exon 1 of HTR2A (chromosome 13q14-21) gene in a large European multicentric case-control sample. Allele and genotype frequencies, as well as homo-heterozygote distributions were compared between the two groups of 309 bipolar affective disorder patients and 309 matched controls. No significant differences were observed in the allelic and genotypic (also for homo-heterozygote) distribution between BPAD and controls. These results indicate that, in our sample, the 5-HT2A receptor polymorphism studied is unlikely to play a major role in the genetic susceptibility to BPAD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:136-140, 2000.
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PMID:A European multicenter association study of HTR2A receptor polymorphism in bipolar affective disorder. 1089 84

Compared to conventional antipsychotic medications, atypical antipsychotic medications demonstrate greater central serotonin (5HT2) receptor antagonism than dopamine type 2 (D2) receptor antagonism. Nefazodone, an antidepressant medication, exhibits 5HT2 receptor antagonism; we therefore wondered if its addition to stable regimens of antipsychotic medication would increase antipsychotic efficacy, independently of a primary effect on mood, through the mechanism of augmented 5HT2 receptor antagonism. In a pilot investigation, we administered nefazodone (400 mg/d) for 6 weeks as an open-label adjunct to antipsychotic medication in 10 patients with chronic schizophrenia. The patients were moderately depressed at baseline but did not meet criteria for major depressive episode. The Brief Psychiatric Rating Scale (BPRS) and Montgomery-Asberg Depression Rating Scale scores showed statistically significant and clinically robust improvements with nefazodone treatment, which were maintained at follow-up evaluation 2 weeks after the end of nefazodone treatment. There were no adverse events. These results suggest that nefazodone may be a safe and effective adjunct to antipsychotic medications in schizophrenia and that augmentation of 5HT2 antagonism may prove to be a viable strategy for "boosting" antipsychotic efficacy and for treating depressive symptoms in schizophrenia.
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PMID:Nefazodone in the adjunctive therapy of schizophrenia: an open-label exploratory study. 1102 Jan 29


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