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)

Selective antagonism of serotonin (5-hydroxytryptamine, 5HT) and noradrenaline transport by antidepressants is a key element in the 'amine' hypothesis of affective disorders. Uptake and/or transport sites of 5HT have been reported to be reduced in platelets of patients suffering from depression and in post-mortem brain samples of depressed patients and suicide victims. To date there has been little molecular information available on the structure and regulation of 5HT transporters. Using the polymerase chain reaction with degenerate oligonucleotides derived from two highly conserved regions of the transporters for noradrenaline and gamma-aminobutyric acid (GABA), we have identified a large family of related gene products expressed in rodent brain. One of these products hybridizes to a single 3.7-kilobase RNA restricted to rat midbrain and brainstem, where it is highly enriched within the serotonergic raphe complex. Transfection with a single 2.3-kilobase brainstem complementary DNA clone is sufficient to confer expression of a Na(+)-dependent 5HT transporter upon nonneural cells, with transport selectively and potently antagonized by 5HT uptake-specific antidepressants, including paroxetine, citalopram and fluoxetine.
 ...
PMID:Cloning and expression of a functional serotonin transporter from rat brain. 194 72

[3H]-Imipramine and [3H]-paroxetine label with high affinity a site which is associated with the serotonergic transporter in brain and platelets. The pharmacological profile of inhibition by drugs of [3H]-imipramine and [3H]-paroxetine binding is highly correlated with the potency of the drugs to inhibit the uptake of 5HT. Denervation of serotonergic neurons by electrolytic lesions or with 5,7-dihydroxytryptamine produces marked decreases in the density of [3H]-imipramine as well as [3H]-paroxetine binding. Dissociation kinetic experiments support the view that the substrate recognition site for 5HT is different from the modulatory site which is labelled by [3H]-imipramine or [3H]-paroxetine. The existence of an endogenous ligand acting on the [3H]-imipramine recognition site to modulate the 5HT transporter was proposed by several laboratories. [3H]-Imipramine binding in platelets appears to be a biological marker in depression. Studies carried out in several laboratories report a significant decrease in the Bmax of platelet [3H]-imipramine binding without changes in Kd, when severely depressed untreated patients are compared with healthy volunteers matched for age and sex. The Bmax of platelet [3H]-imipramine binding appears to be a state-dependent biological marker in depression. It is tempting to speculate that the endocoid of the [3H]-imipramine recognition site may play a role in the pathogenesis of depression.
 ...
PMID:Association of [3H]-imipramine and [3H]-paroxetine binding with the 5HT transporter in brain and platelets: relevance to studies in depression. 304 Sep 83

Serotonergic transmission is thought to be central to the aetiology of depression and the therapeutic actions of antidepressant drugs, and the latters' delayed effect has given rise to the hypothesis that an adaptive change may be involved, possibly at the level of gene expression. We have examined this hypothesis by treating rats over a time course of up to 32 days with either imipramine, mianserin, fluvoxamine, citalopram, amoxapine or saline and measuring the levels of mRNAs encoding the 5HT1A, 5HT1B, 5HT1C and 5HT2 receptors, the enzymes tryptophan hydroxylase and aromatic amino acid decarboxylase, and the 5HT transporter. None of the treatments gave rise to significant changes in any of the mRNA levels at any time point. These results suggest that the reported changes in 5HT receptor numbers do not occur as a result of changes in the abundance of their encoding mRNAs, and that changes to the latter is not central to the therapeutic effects of antidepressant drugs.
 ...
PMID:Lack of effect of antidepressant drugs on the levels of mRNAs encoding serotonergic receptors, synthetic enzymes and 5HT transporter. 798 81

The serotonin (5-HT) transporter (5-HTT) is known to play a role in depression and many 5-HT related diseases, and is the target site for drugs of abuse, such as cocaine, MDMA, and methamphetamine. The major role of the 5-HTT has long been considered to be to inactivate serotonin transmission through the elimination of serotonin at release sites. However, immunocytochemistry using an antibody against the N-terminal of the 5-HTT at the light microscopic (LM) level indicates that the 5-HTT is associated not only with 5-HT varicosities but also with axons. Electron microscopy (EM) reveals that the majority of the 5-HTTs exist on the axolemma outside the synaptic junctions. In studying whether axonal 5-HTTs are involved in the uptake of 5-HT, we found with autoradiography that [3H]citalopram bound to all major 5-HT fibers, not only in the terminal regions, but also in 5-HT axonal bundles such as the cingulum bundle and medial forebrain bundle. Furthermore, voltammetry recordings indicated that serotonin axonal bundles were actively engaged in high affinity serotonin uptake. The evidence indicates that 5-HTTs on 5-HT axons away from the synapse are likely to be functional in a manner similar to the terminal 5-HTT for serotonin uptake. It also suggests that the role of the 5-HTT may not only be for the termination of synaptic transmission, but also for the regulation of 5-HT through extrasynaptic (volume) transmission. Our findings may also impact the understanding of the sites of action of selective serotonin reuptake inhibitors and drug entry into serotonin neurons via the numerous axonal sites.
 ...
PMID:Serotonin transporters are located on the axons beyond the synaptic junctions: anatomical and functional evidence. 973 75

Depression with psychotic features has been shown to respond to selective serotonin reuptake inhibitors (SSRIs). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was recently reported. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antidepressant response to fluvoxamine and/or augmentation with pindolol (a serotonin autoreceptors antagonist) which has been suggested as an augmentation therapy for nonresponders. One hundred and two inpatients with major depression with psychotic features were randomly assigned to treatment with a fixed dose of fluvoxamine and either placebo or pindolol for 6 weeks. Depression severity was assessed once a week using the Hamilton Depression Rating Scale. Allelic variation in each subject was determined using a PCR-based method. Data were analyzed with a three-way repeated measures analysis of variance. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to fluvoxamine than homozygotes for the short variant (s/s). In the group treated with fluvoxamine plus pindolol all the genotypes acted like l/l treated with fluvoxamine alone. Fluvoxamine efficacy in delusional depression seems to be related to allelic variation within the promoter of the 5-HTT gene. Even though other factors may be implicated, genotyping at 5-HTT promoter may represent a promising tool to individualize the pharmacological treatment of depression.
 ...
PMID:Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. 1082 34

We determined polymorphism in the serotonin (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) in 501 healthy Japanese, individuals, using the polymerase chain reaction of Lesch et al., with minor modifications. The distribution of allele frequencies was determined and found to differ from that in Caucasians. We also investigated the relationship of polymorphism in 5-HTTLPR to anxiety traits, by having 189 of the 501 subjects complete a self-rating questionnaire for anxiety and depression. Subjects with the short/short (s/s) genotype had significantly higher anxiety scores than those with the long/long (l/l) or l/s genotype. It is suggested that populations with the s/s genotype of 5-HTTLPR have stronger anxiety-related personality traits than those with the 1 allele.
 ...
PMID:Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese. 992 70

The serotonin transporter gene is a primary candidate for involvement in major psychoses. A functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has recently been reported to be associated with a variety of psychopathological conditions. In the present study, we investigated the potential influence of the 5-HTTLPR on the psychopathology of schizophrenia. One hundred and sixty-one inpatients affected by schizophrenia (DSMIII-R) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were typed for their 5-HTTLPR variants by PCR techniques. Mania, Depression, Delusion and Disorganization were the four symptomatologic factors used to define phenotype. 5-HTTLPR variants 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. The serotonin transporter gene is not a liability factor for the symptomatology of schizophrenia.
 ...
PMID:Serotonin transporter gene is not associated with symptomatology of schizophrenia. 998 39

There is some evidence that the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) may be involved in the pathogenesis of seasonal affective disorder (SAD). Short-term tryptophan (TRP) depletion was carried out in 18 drug-free remitted patients who met DSM-IV criteria for SAD. Behavioral effects were measured with the Hamilton Depression Rating Scale (HDRS) both 24 h before and 24 h after TRP depletion. Some of the patients showed behavioral responses such as lowered mood, feelings of guilt, loss of interest, agitation, loss of energy, fatigue, social withdrawal, increased appetite, and carbohydrate craving. It was the aim of our study to investigate whether the genotypes of the serotonin transporter gene were associated with symptoms of transient depressive relapse after TRP depletion. In addition, we matched the SAD patients with healthy control subjects to see if alleles and genotypes of the serotonin transporter gene were associated with SAD. High molecular weight DNA was isolated from peripheral blood leukocytes using standard methods. For the 5-HTT receptor gene, a 17-bp repetitive element of intron 2 was genotyped (variable number tandem repeat, VNTR). Alterations in HDRS scores after TRP depletion showed no significant association with alleles or genotypes of the 5-HTT gene, although heterozygotes showed a trend toward increased HDRS scores. The serotonin transporter is known to play a critical role in the termination of serotonergic neurotransmission by sodium-dependent uptake of 5-HT into the presynaptic neuron. The present study in a small group of SAD patients was unable to demonstrate that the 5-HTT gene plays a role in the pathogenesis of SAD or in short-term depressive relapse after TRP depletion.
 ...
PMID:Behavioral effects of tryptophan depletion in seasonal affective disorder associated with the serotonin transporter gene? 1033 77

A functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has been recently reported to be associated with mood disorders. In the present study we investigated the possible influence of 5-HTTLPR on the symptomatology of mood disorders. Two hundred and thirty inpatients affected by mood disorders (160 bipolar and 70 major depressive disorder) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were also typed for the 5-HTTLPR variants using PCR techniques. Mania, Depression, Delusion and Disorganization were the four symptomatologic factors used as phenotype definition. 5-HTTLPR variants were not associated with these symptomatologic factors, and consideration of possible stratification effects, such as sex, age of onset and polarity, did not reveal any association either. The serotonin transporter gene does not, therefore, appear to be associated with the symptomatology of mood disorders.
 ...
PMID:Serotonin transporter gene not associated with psychotic symptomatology of mood disorders. 1035 82

Disturbances of the serotoninergic neutrotransmitter system have been implicated in the pathogenesis of mood disorders. A functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has been recently reported to be associated with both unipolar and bipolar disorder. In this study, we investigated the possibility that the 5-HTTLPR might be associated with depressive symptomatology in a sample of mood disorder subjects. One hundred and thirty-two psychiatric inpatients affected by major depressive (n = 67) and bipolar (n = 65) disorder (DSM-IV) were assessed at admission by the Hamilton Depression Rating Scale (HAMD-21, divided into Core, Sleep, Activity, Psychic anxiety, Somatic anxiety and Delusion clusters) and were typed using PCR techniques. The only prior treatment permitted was low dose benzodiazepines (<5 mg diazepam or equivalent); no prior (<2 weeks) antidepressant or neuroleptic treatment was allowed. 5-HTTLPR variants were not associated with total depressive symptomatology as measured by HAMD. The short 5-HTTLPR variant was marginally associated with higher psychic anxiety scores (F = 7.11, d.f. = 1,262, P = 0.008). The association was stronger among bipolars and early onset subjects. 5-HTTLPR variants were not associated with the remaining symptom clusters. The upstream regulatory region of the serotonin transporter gene has not, therefore, a major influence on the depressive symptomatology in mood disorder subjects.
 ...
PMID:Serotonin transporter gene (5-HTTLPR) is not associated with depressive symptomatology in mood disorders. 1039 20


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