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)

Associations of the VNTR-17 and 5-HTTLPR polymorphisms of the serotonin transporter gene with affective disorders, including depression, have been found. These polymorphisms were analyzed in two groups of Russian probands: patients with endogenous psychoses and control individuals without mental disorders (423 and 277 persons, respectively). No associations were found between VNTR-17 genotypes or alleles and the diseases. However, the frequency of 10/10 (VNTR-17) homozygotes increased with age in both patients and healthy persons. The results of the analysis of the 5-HTTLPR polymorphism suggest an association of the short (s) allele of the 5-HTTLPR polymorphism with schizophrenia and schizoaffective psychoses, but not with affective disorders.
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PMID:[Polymorphism in the human serotonin transporter gene in endogenous psychoses]. 1119 Apr 80

Serotonin (5-HT) is an important mediator of interactions between the nervous and immune systems. 5-HT signaling is regulated by the 5-HT transporter (5-HTT), which determines the magnitude and duration of serotonergic responses. Due to this important role, regulation of the 5-HTT by cytokines has been the focus of recent interest. A number of proinflammatory cytokines, including interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma, have been shown to upregulate the 5-HTT. In the present study we investigated the influence of interleukin-4 (IL-4), which acts as an anti-inflammatory cytokine in the central nervous system, on the 5-HTT. As a model system we used immortalized B lymphocytes, which not only express the 5-HTT, but also allow testing the co-modulatory influence of a recently described polymorphism in the 5-HTT gene promoter (5-HTTLPR) that is associated with anxiety- and depression-related behavioral traits. The results show that IL-4 induces a dose-dependent reduction of 5-HT uptake. This effect is preferentially seen in cell lines homozygous for the long, high-activity allele of the 5-HTTLPR. In conclusion, a picture of differential modulation of the 5-HTT by proinflammatory and anti-inflammatory cytokines is emerging, which may represent a fine-tuned mechanism to communicate the state of an immune response to the central nervous system.
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PMID:Modulation of serotonin transporter function by interleukin-4. 1121 57

The antidepressive actions of electroconvulsive shock (ECS) therapy are considered to involve altered neurotransmission of serotonin. In this study, we investigated the effects of acute and chronic ECS on 5-hydroxytryptamine (5-HT) transporter mRNA expression in rat raphe nucleus. We found that serotonin transporter (5-HTT) mRNA expression was decreased in 9 and 24 h after acute ECS and in 3, 9, 24 h and 2 weeks after chronic ECS in rat raphe nucleus. We presume that the adaptive change in 5-HTT mRNA expression is possibly related to the therapeutic efficacy of electroconvulsive therapy (ECT) on medication-resistant depression.
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PMID:Electroconvulsive shock regulates serotonin transporter mRNA expression in rat raphe nucleus. 1123 62

Genetic studies of seasonal affective disorder (SAD) and seasonality have received considerable attention over the past several years. Studies of the prevalence of SAD and nonseasonal mood disorders among relatives of patients with SAD suggested a familial contribution to the development of SAD. Two twin studies demonstrated a substantial role of genetic variation in seasonality. Two genetic variants related to serotonergic transmission, the 5-HTTLPR and the 5-HT(2A)-1438G/A gene promoter polymorphisms, have been found to be associated with SAD. 5-HTTLPR is also associated with seasonality in SAD patients and in the general population. It is not clear whether SAD is inherited as a distinct entity or whether seasonality and depression are separate heritable traits that happen to coincide in certain individuals. Vulnerability to SAD and disease pathology may be influenced by many genes, perhaps on several chromosomes.
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PMID:Genetic studies of seasonal affective disorder and seasonality. 1124 45

The selective serotonin re-uptake inhibitors (SSRIs) which modulate serotonergic activity are effective in the treatment of serotonin-related mental disorders, such as depression and anxiety. These agents bind to the serotonin transporter (5-HTT) and inhibit its capacity to transport serotonin (5-hydroxytryptamine; 5-HT). A functional polymorphism in the promoter region of 5-HTT (5-HTTLPR) has been described. The insertion variant of this polymorphism (long allele) is associated with higher expression of brain 5-HTT compared to the deletion variant (short allele). An association between the 5-HTTLPR polymorphism and mental disorders has been reported by some, but not all, investigators. In addition, the 5-HTT gene polymorphisms were found to be associated with a better and faster response to SSRIs with or without pindolol augmentation in depressed patients. Further studies are needed to clarify the relationship between the 5-HTT genotype, the susceptibility to mental disorders, the response to serotonergic agents and the side effect profile.
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PMID:Serotonin transporter polymorphism and response to SSRIs in major depression and relevance to anxiety disorders and substance abuse. 1125 82

Although increasing evidence suggests that selective serotonin reuptake inhibitor (SSRI) treatment may be effective for anxiety in addition to depression, SSRI anxiolysis has not been definitively related to the inhibition of serotonin (5-HT) transport. The gene that encodes for the human serotonin transporter (5-HTT) expresses its protein in neurons and in blood platelets, and both tissues respond to transport inhibition similarly in response to SSRI treatment. This study examined the relationship between the change in the 5-HTT's apparent affinity for 5-HT and the anxiolytic response in a group of 18 fluvoxamine-treated patients meeting Structured Clinical Interview for DSM-IV criteria for both generalized anxiety disorder and major depression. Significant decreases were found in both Hamilton anxiety and Hamilton depression scores over a 2-month treatment period. Robust increases were found in the apparent affinity constant (Km) for platelet 5-HT transport with treatment, and the increases covaried significantly with the decrease in anxiety (F = 4.97, p < 0.03). The pretreatment 5-HTT Km significantly correlated with the improvement in depression scores (r = 0.53, p < 0.03), consistent with the Hypothesis of Initial Conditions. These results suggest that the therapeutic effect of SSRI treatment can be linked to the magnitude and time-course of 5-HT transport inhibition effected with fluvoxamine, a drug that seems to have an antianxiety effect of the same magnitude as its effect on depression.
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PMID:Fluvoxamine treatment of mixed anxiety and depression: evidence for serotonergically mediated anxiolysis. 1127 Sep 9

Although 30-60% of the variance in many personality traits is inherited, until recently, little was known about the genes responsible. Preliminary studies of family history in bipolar disorder and of X-linkage of personality traits in colour-blindness suggested a 'quantitative trait locus' (QTL) approach to the genetics of normal personality. In methodically similar but independent studies of 124 Israeli and 315 American normal volunteers, an association was found between the dopamine D4 receptor gene (D4DR) and the personality trait of novelty-seeking. In the Israeli sample there was preliminary evidence for an interaction between the D4DR gene and the serotonin 2C receptor gene (5-HT-2C), with a marked effect on the trait of reward dependence. In addition to receptors, monoamine uptake mechanisms, such as the serotonin transporter (5-HTT), are candidate genes for personality traits. 5-HTT gene transcription is modulated by a frequent polymorphism in its promoter region, with resulting effects on 5-HTT expression and 5-HT uptake. In an extended American sample totalling 505 subjects, the 5-HTT polymorphism was associated with anxiety- and depression-related personality traits. The allelic variation in functional expression of the 5-HTT may also be a susceptibility factor for disorders of the affective spectrum. Further investigation of genes for personality traits may provide additional links between normal personality and psychiatric illness.
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PMID:Genes for personality traits: implications for psychopathology. 1128 59

Biogenic amine transporters, namely the dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (serotonin, 5-HT) transporters (DAT, NET and 5-HTT, respectively) appear to be the key elements in regulating biogenic amine neurotransmission. These proteins therefore represent a primary target for therapeutic intervention in the treatment of numerous psychiatric disorders, such as depression, anxiety and perhaps even schizophrenia as well as drug abuse. The cloning of DAT, NET and 5-HTT and development of selective radioligands for them over the last decade has dramatically increased our understanding of their location, structure and function. These breakthroughs have also enabled remarkable progress in determining how biogenic amine transporters are regulated under not only normal conditions but also when confronted with acute or chronic exposure to a variety of stimuli including psychotherapeutic drugs. Because of the important therapeutic consequences of a better understanding of these transporters, the present review discusses recent advances in defining their mechanism of action, location and regulation and the implications of the newer data for neuropsychopharmacology.
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PMID:New views of biogenic amine transporter function: implications for neuropsychopharmacology. 1128 47

In children and adolescents, hyperkinetic disorder (HD) with conduct disorder (CD) and without CD and attention-deficit/hyperactivity disorder (ADHD) is known to be comorbid with psychiatric disorders (anxiety, depression, aggression), some of which are related to disturbed serotonergic neurotransmission. The efficiency of serotonergic signalling relates to the concentration of the neurotransmitter in the synaptic cleft and is controlled by the serotonin transporter (5-HTT), which selectively removes serotonin out of the synaptic cleft.(1)The activity of serotonin transport itself has been shown to be also controlled by a 5-HTT-linked polymorphism in its promotor region with a L/L genotype yielding higher levels of 5-HTT function than do L/S or S/S genotypes.(2) Considering an association between 5-HTT polymorphism, serotonergic neurotransmission and HD +/- CD, we genotyped for 5-HTT polymorphism and compared patients with controls. In contrast to the distribution of L/L: L/S: S/S in controls (0.245: 0.509: 0.245), we found an enhanced expression of the L/L genotype in HD patients with CD (0.393: 0.304: 0.304; chi(2) = 7.603; P = 0.0211) and a significant overexpression of L/L in HD without CD (0.542: 0.333: 0.125; chi(2) = 9.127; P = 0.0092). To our knowledge, this is the first finding providing evidence for an association between the 5-HTT polymorphism and hyperkinetic disorder, implying that serotonergic neurotransmission might be affected in this desease. As a consequence, for a successful treatment of these patients one should now also consider drugs which specifically modulate serotonergic signalling such as selective serotonin reuptake inhibitors.
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PMID:Functional polymorphism within the promotor of the serotonin transporter gene is associated with severe hyperkinetic disorders. 1131 29

Idiopathic Parkinson's disease (PD) is a common neurodegenerative disorder with prominent motor symptoms. However, depression is common in PD, affecting about 40% of PD patients. Since there is extensive evidence of degeneration of serotonin (5HT) neurons and loss of the 5HT transporter (5HTT) in PD, we assessed whether a functional polymorphism in the promoter of the 5HTT gene (5HTT gene-linked polymorphic region, 5HTTLPR), which determines high or low 5HT uptake, is associated with depressive symptomatology in PD patients. We found that patients with the short allele of the 5HTTLPR had significantly higher scores on the Hamilton Depression Scale. A functional promoter polymorphism of the monoamine oxidase A (MAOA) gene showed no association. Thus, the 5HTTLPR but not the MAOA gene promoter-associated polymorphism may be a risk factor for depression in PD patients, while neither polymorphism increases the risk for development of Parkinson's disease itself.
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PMID:Allelic variation of serotonin transporter expression is associated with depression in Parkinson's disease. 1132 8


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