Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevailing neurochemical theory about biological correlates of suicidal behavior focuses on the serotonergic system. In this study, we assessed the cortisol, ACTH, GH, prolactin and temperature responses to flesinoxan, a5-HT1A agonist, in 30 DSM-III-R major depressed inpatients subgrouped into suicide attempters (n = 15) and nonattempters (n = 15). The patients were assessed after a drug-free period of at least 3 weeks. A subsample of 16 patients completed the Buss-Durkee Hostility Inventory as a measure of impulsive aggressive behavior. Mean delta cortisol responses to flesinoxan were significantly lower in the group of depressed patients with a history of suicide attempts than in the group without history of suicidal behavior: for the delta cortisol values 14.5 +/- 16.3 micrograms/l vs 101 +/- 94 micrograms/l (F = 8.9, df = 5.25, p = 0.006). There was also a very significant difference between suicide attempters and nonattempters for the temperature (delta T degrees) responses to flesinoxan: 0.20 +/- 0.24 degrees C vs. 0.60 +/- 0.24 degrees C (F = 18.1, df = 5.25, p = 0.0003). Hormonal and temperature responses to flesinoxan were not correlated with BDHI irritability or assault subscale scores. The results of the present study support the implication of the serotonergic system, particularly 5-HT1A receptors, in the control of self-directed aggressive behavior. Moreover, in depressed patients, serotonergic abnormalities do not appear to be related to aggressive behavior.
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PMID:The flesinoxan 5-HT1A receptor challenge in major depression and suicidal behavior. 861 6

Significant progress has been made in understanding psychosocial, psychological, and environmental factors associated with suicide; however, it is only recently that attention has been paid to the understanding of the neurobiology of suicide. There are several studies that implicate the serotonin (5-HT) system in suicide. Initial evidence was obtained from observations of low 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) of depressed patients with a previous history of suicide attempts. Several strategies have been used to examine the serotonergic system in suicidal behavior, which include the determination of serotonin and its metabolites in CSF and postmortem brain tissues as well as serotonin receptor subtypes in postmortem brain tissues, and in platelets of suicidal patients. The neuroendocrine strategy, often termed the "window to the brain," has been extensively used for studying the serotonergic system in suicide. This chapter will review the results obtained from neuroendocrine and serotonin studies in platelets. Initial studies in platelets focussed on determining serotonin uptake and serotonin transporter binding sites in platelets of depressed and suicidal patients. Whereas several studies have found decreased imipramine binding sites of platelets of depressed patients, imipramine binding sites in platelets of suicidal patients showed inconsistent results. Similarly, no consistent changes in 5-HT uptake have been observed in platelets obtained from suicidal patients compared to nonsuicidal patients. On the other hand, studies of platelet 5-HT2A receptors appear to be quite encouraging. Initially, several investigators indicated that they found an increase in platelet 5-HT2A receptors in depressed patients. Subsequently, it was shown that platelet 5-HT2A receptors in suicidally depressed patients were significantly higher compared to nonsuicidally depressed patients and normal control subjects. It has also been shown that platelet 5-HT2A receptors are increased in suicidal patients independent of diagnosis, similar to platelets. 5-HT2A receptors have also been shown to be increased in the postmortem brain of suicide victims by several investigators, although some investigators do not find such an increase. The neuroendocrine strategy provides an important method for studying serotonin function in the central nervous system of depressed and suicidal patents. Using a serotonergic probe of 5-HT1A receptors, several investigators examined ipsapirone-induced prolactin release in suicidal patients and did not find it different that that of control subjects. On the other hand, fenfluramine, which causes release of serotonin and blocks serotonin uptake, causes a decreased release of prolactin in depressed patients compared to normal control subjects. Furthermore it has been shown by some investigators that fenfluramine-induced prolactin release is also decreased in suicidal patients compared to normal control subjects. In summary, platelet and neuroendocrine studies have provided initial evidence sufficient to suggest serotonergic abnormalities in suicidal patients. Most earlier evidence is based on CSF 5-HIAA studies, but it appears that 5-HT2A receptors in both platelet and postmortem brain samples are increased in suicidal patients. The observation that platelet 5-HT2A receptors are increased in suicidal patients independent of diagnosis provides a very useful potential biological marker for identifying suicidal patients.
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PMID:Altered serotonin function in suicide. Evidence from platelet and neuroendocrine studies. 961 99

A serotonergic dysfunction in the brain has been reported to be involved in suicidal behavior independently of the presence of a specific psychiatric disorder. Serotonin 1A (5-HT1A) receptors are known to be located on serotonergic nerve terminals and to be involved in the presynaptic regulation of serotonin release. Genetic factors partly explain the risks for suicide, and a suicide completion group is thought to be more uniform than a suicide attempt group. To explore the hypothesis that the 5-HT1A receptor-induced serotonergic dysfunction is implicated genetically in suicide, we focused on the structural polymorphisms, Pro16Leu and Gly272Asp, of the 5-HT1A receptor gene, and examined the association between suicide victims who completed suicide and these two polymorphisms. In both polymorphisms, we found no significant difference in genotype distribution or allele frequencies between suicide victims and controls. These findings suggest that neither of these two polymorphisms is associated with suicide victims and it is unlikely that the 5-HT1A receptor gene is implicated in the susceptibility to suicide.
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PMID:Lack of an association between 5-HT1A receptor gene structural polymorphisms and suicide victims. 1199 64

The 5HT1A receptor is one of at least 14 different receptors for serotonin which has a role in moderating several brain functions and may be involved in the aetiology of several psychiatric disorders. The C(-1019)G 5-HT1A promoter polymorphism was reported to be associated with major depression, depression-related personality traits and suicidal behavior in various samples. The G(-1019) allele carriers are prone to depressive personality traits and suicidal behavior, because serotonergic neurotransmission is reduced. The aim of this study is to replicate previous findings in a sample of 185 Alcohol-dependent individuals. Personality traits were evaluated using the NEO FFI and TCI. History of suicidal behavior was assessed by a standardized semistructured interview (SSAGA). No significant differences across C(-1019)G 5-HT1A genotype groups were found for TCI temperament and character traits and for NEO FFI personality scales. No association was detected between this genetic variant and history of suicide attempts. These results neither support a role of C(-1019)G 5-HT1A promoter polymorphism in the disposition of personality traits like harm avoidance or neuroticism, nor confirm previous research reporting an involvement of the G allele in suicidal behavior in alcoholics. Significant associations, however, were detected between Babor's Type B with number of suicide attempts in history, high neuroticism and harm avoidance scores in alcoholics.
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PMID:The C(-1019)G 5-HT1A promoter polymorphism and personality traits: no evidence for significant association in alcoholic patients. 1650 34

Suicide affects about one million people each year, a phenomenon characterized by heterogeneous and complex causes. Often environmental factors such as negative life events may act as a significant contributor to suicidal behavior. However, in many cases the exposure to the same environmental stress does not result in increased suicidality. It is now well established that there is also a substantial genetic contribution to suicidal behavior. Here, functional and association studies which implicate specific genes in psychological traits and environmental factors are discussed, interactions which are related to completed suicide or suicide attempt, and our novel findings which need replication are presented. We found that genetic variation in the noradrenergic tyrosine hydroxylase gene was associated with the angry/hostility personality trait and vulnerability to stress. Similarly, we recently discovered that genetic variation in components of the stress-related hypothalamic pituitary adrenocortical axis, T-box 19 and corticotropin releasing hormone receptor 1, showed association and linkage to high anger/hostility in and male depression the suicidal offspring, respectively. Further results from our studies have revealed that genetic variation in genes with roles in basal mechanisms of neural conduction, voltage-gated sodium channel type VIII alpha and vesicle-associated membrane 4 protein, showed association and linkage among suicide attempters. Additionally, we have results which give support to the findings of others, implicating the serotonin transporter and serotonin receptor 1A in suicidal behavior. Our future studies aim at identifying and resolving complex patterns and mechanisms of neurobiological gene-environment interactions, which may contribute to suicide.
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PMID:Nature and nurture in suicidal behavior, the role of genetics: some novel findings concerning personality traits and neural conduction. 1758 62

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

Implication of serotonergic system in suicide and suicide attempts has been discussed for several years. One of the most abundant serotonin receptors in the mammalian brain is the receptor 1A (5-HT1A); studies of its polymorphisms and suicide have provided very inconsistent results so far. The suggestion that the G allele depresses HTR1A autoreceptor expression, and therefore reduces serotonergic neurotransmission that might predispose to depression and suicide, made the promoter polymorphism -1019C>G a very promising candidate gene. In our study we analyzed promoter polymorphism -1019C>G on 323 suicide victims and 190 controls (all of Slovenian origin), taking into account sex, suicide method, and in case of suicide victims also stressful life events. Differences in the distributions of genotype and allele frequencies were not statistically significant between suicide victims and control group, and the same was found for distributions according to sex and suicide method. For 62 suicide victims information about stressful life events in the month prior to the suicide and in childhood was provided. For analysis we combined CG/GG genotypes and compared them to the CC genotype. More stressful life events in the month prior to the suicide were reported for the subgroup with CC genotype (mean number of events = 2.53; SD = 1.50) in comparison to subgroup with CG/GG genotypes (mean number of events = 1.58; SD = 1.32; P < 0.05). However, subgroups of suicide victims with CC or CG/GG genotypes did not differ regarding numbers of reported stressful life events in childhood (P > 0.05). Our study provides no evidence for the implication of HTR1A promoter polymorphism in suicide in general, but it suggests further studies that would take into account the interconnected network of suicide completion, genetic background and stress, beside other risk factors.
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PMID:Suicide, stress and serotonin receptor 1A promoter polymorphism -1019C>G in Slovenian suicide victims. 1922 12

The World Health Organization estimates that almost one million deaths each year are attributable to suicide, and suicide attempt is close to 10 times more common than suicide completion. Suicidal behaviour has multiple causes that are broadly divided into proximal stressors or triggers and predisposition such as genetic. It is also known that single nucleotide polymorphisms (SNPs) occur throughout a human DNA influencing the structure, quantity and the function of proteins and other molecules. Abnormalities of the serotonergic system were observed in suicide victims. Beside 5-HT1A and other serotonin receptors most studied are the serotonin transporter 5' functional promoter variant, and monoamine oxidase A and the tryptophan-hydroxylase 1 and 2 (TPH) polymorphisms. It seems that especially genes regulating serotoninergic system and neuronal systems involved in stress response are associated with suicidal behaviour. Most genetic studies on suicidal behaviour have considered a small set of functional polymorphisms relevant mostly to monoaminergic neurotransmission. However, genes involved in regulation of other factors such as brain-derived neurotropic factor seems to be even more relevant for further research.
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PMID:Single nucleotide polymorphisms and suicidal behaviour. 2294 90

Bipolar disorder is a pernicious illness. Compared with the later-onset form, early onset bipolar disorder is associated with worse psychosocial outcomes, and is characterized by rapid cycling and increased risks of substance abuse and suicide attempts. Controlling mood episodes and preventing relapse in this group of pediatric patients requires careful treatment. Here, we review the effectiveness of aripiprazole for bipolar disorder in children and adolescents, with discussion of this drug's unique pharmacological profile and various clinical study outcomes. Aripiprazole acts as a serotonin 5-HT2A receptor antagonist, as well as a partial agonist of the serotonin 5-HT1A and dopamine D2 receptors. It can be safely used in children and adolescents, as it is highly tolerated and shows lower rates of the side effects typically observed with other antipsychotic drugs, including sedation, weight gain, hyperprolactinemia, and extrapyramidal syndrome. The presently reviewed randomized controlled trials (RCTs) and non-RCTs generally reported aripiprazole to be effective and well-tolerated in children and adolescents with bipolar disorder. However, due to the limited number of RCTs, the present conclusions must be evaluated cautiously. Furthermore, aripiprazole cannot yet be considered a preferred treatment for children and adolescents with bipolar disorder, as there is not yet evidence that aripiprazole shows greater efficacy compared to other second-generation antipsychotics. Additional data are needed from future head-to-head comparison studies.
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PMID:Profile of aripiprazole in the treatment of bipolar disorder in children and adolescents. 2547 24