Functional promoter polymorphism of the neuronal isoform of tryptophan hydroxylase (Tph2) in suicide

Štefulj, Jasminka; Mokrović, Gordana; Hranilović, Dubravka; Bordukalo-Niksic, Tatjana; Bakula, Mirko; Kubat, Milovan; Jernej, Branimir

doi:10.1016/j.psychres.2010.08.034

Cited by 12 publications

(7 citation statements)

References 20 publications

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“…Yoon et al (Yoon and Kim, 2009) showed a positive association of rs4570625 with suicide attempt and concluded that the observed increased frequency of G allele may be associated with elevated suicidal behaviour. Several other studies, however, did not confirm this association (Mouri et al, 2009; Stefulj et al, 2011; Zhou et al, 2005; Zill et al, 2007). The human TPH2 promoter polymorphism rs11178997 is another SNP in the promotor region that has an impact on TPH2 expression (Chen et al, 2008), but according to results obtained by several different groups (De Luca et al, 2005b; Lopez et al, 2007; Must et al, 2009; Zhou et al, 2005), it has no impact on suicide attempt and completion.…”

Section: The Serotonergic System In Aggression and Suicidementioning

confidence: 78%

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: 78%

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

et al. 2013

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“…In addition, links have been reported between suicide and SNPs located between TPH2 exons 5 and 7 (91), in intron 1, intron 8, and the 5′ upstream region (92). However, no link was found between suicide and the G703T SNP (93) or multiple other TPH2 polymorphisms (94). …”

Section: Neurotransmitter Systems Implicated In Suicidementioning

confidence: 96%

Toward a Biosignature for Suicide

Oquendo¹,

Sullivan

Sudol

et al. 2014

AJP

258

210

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Objective Suicide, a major cause of death worldwide, has distinct biological underpinnings. The authors review and synthesize the research literature on biomarkers of suicide, with the aim of using the findings of these studies to develop a coherent model for the biological diathesis for suicide. Method The authors examined studies covering a large range of neurobiological systems implicated in suicide. They provide succinct descriptions of each system to provide a context for interpreting the meaning of findings in suicide. Results Several lines of evidence implicate dysregulation in stress response systems, especially the hypothalamic-pituitary-adrenal axis, as a diathesis for suicide. Additional findings related to neuroinflammatory indices, glutamatergic function, and neuronal plasticity at the cellular and circuitry level may reflect downstream effects of such dysregulation. Whether serotonergic abnormalities observed in individuals who have died by suicide are independent of stress response abnormalities is an unresolved question. Conclusions The most compelling biomarkers for suicide are linked to altered stress responses and their downstream effects, and to abnormalities in the serotonergic system. Studying these systems in parallel and in the same populations may elucidate the role of each and their interplay, possibly leading to identification of new treatment targets and biological predictors.

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“…It would be highly interesting to investigate whether such in vitro effects also translate to alterations in Tph2 protein expression and 5-HT levels, and 5-HT neurotransmission in vivo, particularly because, in contrast to functional Tph2 SNPs that generally are rare, non-coding SNPs appear more common. For instance, the T-703G SNP is detected in most cohorts examined [116][117][118][119].…”

Section: Tph2: Depression and Suicidalitymentioning

confidence: 99%

The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2^Arg439^Hisknockin mouse

Jacobsen

Medvedev

Caron

2012

Phil. Trans. R. Soc. B

161

105

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A decreased level of brain 5-hydroxytryptamine (5-HT) has been theorized to be a core pathogenic factor in depression for half a century. The theory arose from clinical observations that drugs enhancing extracellular levels of 5-HT (5-HT Ext ) have antidepressant effects in many patients. However, whether such drugs indeed correct a primary deficit remains unresolved. Still, a number of anomalies in putative biomarkers of central 5-HT function have been repeatedly reported in depression patients over the past 40 years, collectively indicating that 5-HT deficiency could be present in depression, particularly in severely ill and/or suicidal patients. This body of literature on putative 5-HT biomarker anomalies and depression has recently been corroborated by data demonstrating that such anomalies indeed occur consequent to severely reduced 5-HT Ext levels in a mouse model of naturalistic 5-HT deficiency, the tryptophan hydroxylase 2 His 439 knockin (Tph2KI) mouse. In this review, we will critically assess the evidence for 5-HT deficiency in depression and the possible role of polymorphisms in the Tph2 gene as a causal factor in 5-HT deficiency, the latter investigated from a clinical as well as preclinical angle.

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Functional promoter polymorphism of the neuronal isoform of tryptophan hydroxylase (Tph2) in suicide

Cited by 12 publications

References 20 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

Toward a Biosignature for Suicide

The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2^Arg439^Hisknockin mouse

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Functional promoter polymorphism of the neuronal isoform of tryptophan hydroxylase (Tph2) in suicide

Cited by 12 publications

References 20 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

Toward a Biosignature for Suicide

The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439Hisknockin mouse

Contact Info

Product

Resources

About

The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2^Arg439^Hisknockin mouse