Lack of an association between 5‐HT<sub>6</sub> receptor gene polymorphisms and suicide victims

Okamura, Kenji; Sato, Osamu; Nishiguchi, Naoki; Ono, Hitoshi; Nushida, Hideyuki; Ueno, Yoshio; Maeda, Kiyoshi

doi:10.1111/j.1440-1819.2005.01380.x

Cited by 18 publications

(5 citation statements)

References 32 publications

(53 reference statements)

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“…Initial studies appear to implicate a significant up-regulation of 5-HT 4 receptors in the frontal cortex and caudate nucleus of depressed suicide victims (Rosel et al, 2004). Studies on the C267T polymorphism of the human 5-HT6 gene have shown a possible implication of this SNP in suicide of male patients (Azenha et al, 2009; but see Okamura et al, 2005 for contrasting findings). The same SNP was not found in association with aggressive behaviour in schizophrenia patients (Tsai et al, 1999).…”

Section: The Serotonergic System In Aggression and Suicidementioning

confidence: 99%

The role of the serotonergic system at the interface of aggression and suicide

et al. 2013

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Alterations in serotonin (5-HT) neurochemistry have been implicated in the aetiology of all major neuropsychiatric disorders, ranging from schizophrenia to mood and anxiety-spectrum disorders. This review will focus on the mulifaceted implications of 5-HT-ergic dysfunctions in the pathophysiology of aggressive and suicidal behaviours. After a brief overview of the anatomical distribution of the 5-HT-ergic system in the key brain areas that govern aggression and suicidal behaviours, the implication of 5-HT markers (5-HT receptors, transporter as well as synthetic and metabolic enzymes) in these conditions is discussed. In this regard, particular emphasis is placed on the integration of pharmacological and genetic evidence from animal studies with the findings of human experimental and genetic association studies. Traditional views postulated an inverse relationship between 5-HT and aggression and suicidal behaviours; however, ample evidence has shown that this perspective may be overly simplistic, and that such pathological manifestations may reflect alterations in 5-HT homeostasis due to the interaction of genetic, environmental and gender-related factors, particularly during early critical developmental stages. The development of animal models that may capture the complexity of such interactions promises to afford a powerful tool to elucidate the pathophysiology of impulsive aggression and suicidability, and find new effective therapies for these conditions.

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Section: The Serotonergic System In Aggression and Suicidementioning

confidence: 99%

The role of the serotonergic system at the interface of aggression and suicide

et al. 2013

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“…138 Further polymorphisms in the coding and in the promoter region were identified, as the common A-161T polymorphism in the promoter region 139 but two subsequent studies did not find an association to attempted suicide and aggression in Chinese schizophrenics 140 or in Chinese depressives. 141 The other serotonin receptors gained so far less attention and investigations with the 5-HT2C receptor, 142 the 5-HT6 receptor 143 or a combined investigation of seven serotonergic receptor genes revealed no hints of being involved in suicidality. 144 This constantly negative finding on the serotonin receptors other than the two positive findings with the 5-HT2A receptor gene, demonstrates that they seem not to have an impact on the liability for suicidality.…”

Section: Other Serotonergic Receptorsmentioning

confidence: 99%

Genetics of suicide

2006

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The concept that genetic factors contribute to the complex trait of suicidal behaviour has stimulated much work aimed at identifying susceptibility genes. So far molecular genetic studies focused on the serotonergic pathway as the intent to die and the lethality of suicide acts were related to the serotonergic system. Two genes have so far emerged as being involved in the vulnerability for suicidality: first, the intronic polymorphisms (A218C or A779C) of the tryptophan hydroxylase 1 (TPH1) gene, which was suggested as a quantitative risk factor for suicidal behaviour; second, the insertion/deletion polymorphism of the serotonin transporter gene (5-HTTLPR), which does not seem to be involved in general suicidal behaviour, but in violent and repeated suicide attempts. The data have further shown that the MAOA gene, which is consistently associated with impulsive-aggressive personality traits, is not related to suicide but might induce violent methods in subjects with other suicide risk factors. Predominantly negative were the findings with any type of the serotonin receptors and inconsistent with catecholamine-synthesizing and -metabolizing enzymes or with the dopaminergic receptors. This paper reviews the status of current knowledge in this area, points to the weakness of the investigations and presents new approaches beyond the serotonergic system.

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“…116 The 267C>T polymorphism in exon 1 and a trinucleotide repeat polymorphism (2 or 3 GCCrepeats) in the 5′ upstream region of the gene were found not to be associated with suicidal behaviour. 275 β1 adrenoceptor A number of pharmacologically well characterized subtypes of adrenergic receptors are known, including α1, α2, β1 and β2. Of these, both the β1 adrenoceptor (β1AR) and the β2 adrenoceptor (β2AR) stimulate adenylate cyclase, although they are implicated in different physiologic functions.…”

Section: -Ht4 and 5-ht7mentioning

confidence: 99%

Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

161

103

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87Personalized medicine -the adaptation of therapies based on an individual's genetic and molecular profile -is one of the most promising aspects of modern medicine. The identification of the relation between genotype and drug response, including both the therapeutic effect and side effect profile, is expected to deeply affect medical practice. In this paper, we review the current knowledge about the genes related to antidepressant treatment response and provide methodologic proposals for future studies. We have mainly focused on genes associated with pharmacodynamics, for which a list of promising genes has been identified despite some inconsistency across studies. We have also synthesized the main results for pharmacokinetic genes, although so far they seem less relevant than those for pharmaco dynamic genes. We discuss possible reasons for these inconsistent findings and propose new study designs.

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Lack of an association between 5‐HT₆ receptor gene polymorphisms and suicide victims

Cited by 18 publications

References 32 publications

The role of the serotonergic system at the interface of aggression and suicide

The role of the serotonergic system at the interface of aggression and suicide

Genetics of suicide

Pharmacogenetics of antidepressant response

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Lack of an association between 5‐HT6 receptor gene polymorphisms and suicide victims

Cited by 18 publications

References 32 publications

The role of the serotonergic system at the interface of aggression and suicide

The role of the serotonergic system at the interface of aggression and suicide

Genetics of suicide

Pharmacogenetics of antidepressant response

Contact Info

Product

Resources

About

Lack of an association between 5‐HT₆ receptor gene polymorphisms and suicide victims