Suicidality and 5-Hydroxyindoleacetic Acid Concentration Associated With a Tryptophan Hydroxylase Polymorphism

Nielsen, David A.; Goldman, David; Virkkunen, Matti; Tokola, Riitta; Rawlings, Robert R.; Linnoila, Markku

doi:10.1001/archpsyc.1994.03950010034005

Cited by 349 publications

(220 citation statements)

References 33 publications

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“…The first case-control study using the TPH intron 7 polymorphism was carried out by Nielsen et al 27 The results of this preliminary study were confirmed in larger samples. 6 The authors asserted that 'a functional variant in or close to the TPH gene may predispose individuals to suicidality and other behaviors thought to be influenced by serotonin'.…”

Section: Commentsupporting

confidence: 52%

Suicide attempts and the tryptophan hydroxylase gene

et al. 2001

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Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis. In this casecontrol study, we investigated whether the TPH gene was a susceptibility factor for suicidal behavior. Seven polymorphisms spanning the entire gene were studied in a case-control study including 231 individuals who had attempted suicide and 281 controls. Significant associations were found between variants in introns 7, 8 and 9 ( 2 = 11.2, df = 1, P Ͻ 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3Ј noncoding region ( 2 = 30.94, P = 0.0014) and suicide attempt. The association was strongest for subjects who had attempted suicide by violent means and who had a history of major depression. No significant association was observed between suicide attempts and polymorphisms in the promoter, intron 1 and intron 3. The results presented here, and those of previous studies, suggest that a genetic variant of the 3Ј part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression. Molecular Psychiatry (2001) 6, 268-273.

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Section: Commentsupporting

confidence: 52%

Suicide attempts and the tryptophan hydroxylase gene

et al. 2001

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“…Recent molecular genetic studies have emerged providing evidence of polymorphisms in the TPH gene associated with several types of mood disorders (Nielsen et al, 1994;Mann et al, 1997;New et al, 1997;Bellivier et al, 1998). For example, Nielsen and colleagues (1994) examined TPH genotype in impulsive and nonimpulsive violent offenders with a history of suicide attempts and alcohol abuse or dependence.…”

Section: Discussionmentioning

confidence: 99%

Regional Distribution and Cellular Expression of Tryptophan Hydroxylase Messenger RNA in Postmortem Human Brainstem and Pineal Gland

Austin

O’Donnell

1999

Journal of Neurochemistry

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Abstract:The characterization and cellular localization of tryptophan hydroxylase mRNA in the human brainstem and pineal gland were investigated by using northern blot analysis and in situ hybridization histochemistry. Northern analysis of human pineal gland revealed the presence of two mRNA species that were absent in RNA isolated from human raphe. In situ hybridization experiments revealed very dense hybridization signal corresponding to tryptophan hydroxylase mRNA in cells throughout the pineal gland. In contrast, tryptophan hydroxylase mRNA was heterogeneously distributed in neurons in the dorsal and median raphe nuclei. Within the dorsal raphe, the ventrolateral and interfascicular subnuclei contained the greatest number of tryptophan hydroxylase mRNA-positive neurons. Also, the cellular concentration of tryptophan hydroxylase mRNA varied widely within the dorsal and median raphe. Comparison of the cellular concentration of tryptophan hydroxylase mRNA between the pineal gland and the raphe nuclei revealed an 11 -and 46-fold greater average grain density of tryptophan hydroxylase mRNA positive cells in the pineal gland compared with the dorsal and median raphe, respectively. These findings are the first to demonstrate the cellular localization of tryptophan hydroxylase mRNA in the human brain and pineal gland as well as heterogeneity in the cellular concentration within and between these tissues.

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“…Most of the molecular genetic studies on the TPH genes so far have examined the two polymorphisms of the TPH1, A218C and A779C, which have been found to be in complete or strong linkage disequilibrium in previous studies [94]. A polymorphism in intron 7 of TPH1, A218C has been extensively examined in association studies, and the A allele is associated with anxiety symptoms in depression [95].…”

Section: Genetic Epidemiologymentioning

confidence: 99%

Molecular epidemiology of major depressive disorder

Kiyohara

Yoshimasu

2009

Environ Health Prev Med

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Major depressive disorder causes significant morbidity, affecting people's ability to work, function in relationships, and engage in social activities. Moreover, major depressive disorder increases the risk of suicidal ideation, attempted suicide and death by completed suicide. There is evidence that chronic stress can cause major depressive disorder. As for genetic factors, only minor susceptibility genes have been reliably identified. The serotonin system provides a logical source of susceptibility genes for depression, because this system is the target of selective serotonin reuptake-inhibitor drugs that are effective in treating depression. The 5-hydroxytryptamine (serotonin) transporter (5-HTT) has received particular attention because it is involved in the reuptake of serotonin at brain synapses. One common polymorphic variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which affects the promoter of the 5-HTT gene, causes reduced uptake of the neurotransmitter serotonin into the presynaptic cells in the brain. The authors discussed the relationship between genetic polymorphisms and major depressive disorder, with special emphasis on the 5-HTTTLPR polymorphism. As the 5-HTTLPR polymorphism was significantly associated with an increased risk of major depressive disorder, the 5-HTT gene may be a candidate for a major depressive disorder susceptibility gene. As major depressive disorder is a multifactorial disease, an improved understanding of the interplay of environmental and genetic polymorphisms at multiple loci may help identify individuals who are at increased risk for major depressive disorder. Hopefully, in the future we will be able to screen for major depressive disorder susceptibility by using specific biomarkers.

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Suicidality and 5-Hydroxyindoleacetic Acid Concentration Associated With a Tryptophan Hydroxylase Polymorphism

Abstract: In some individuals, a genetic variant of the TPH gene may influence 5-HIAA concentration in the cerebrospinal fluid and predisposition to suicidal behavior.

Cited by 349 publications

References 33 publications

Suicide attempts and the tryptophan hydroxylase gene

Suicide attempts and the tryptophan hydroxylase gene

Regional Distribution and Cellular Expression of Tryptophan Hydroxylase Messenger RNA in Postmortem Human Brainstem and Pineal Gland

Molecular epidemiology of major depressive disorder

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