Tryptophan hydroxylase polymorphisms in suicide victims

Bennett, Pamela J.; McMahon, William M.; Watabe, J.; Achilles, Jennifer; Bacon, Melanie C.; Coon, Hilary; Grey, Todd C.; Keller, Trisha; Tate, David F.; Tcaciuc, I.; Workman, J.; Gray, Douglas

doi:10.1097/00041444-200010010-00003

Cited by 63 publications

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“…t-Tests or Chi-square tests were performed, as appropriate for the measurement, to test for differences concerning sociodemographic variables between the diagnostic subgroups and between the genotype subgroups. Since previous studies on aggression-related traits 15,16 investigated U carriers vs L homozygotes, we used the same groups in an attempt to be comparable with the previous findings. Furthermore, New and colleagues 15 genotyped the A779C and Manuck and colleagues 16 the A218C SNP, which prompted us to genotype both polymorphisms.…”

Section: Discussionmentioning

confidence: 99%

“…Since previous studies on aggression-related traits 15,16 investigated U carriers vs L homozygotes, we used the same groups in an attempt to be comparable with the previous findings. Furthermore, New and colleagues 15 genotyped the A779C and Manuck and colleagues 16 the A218C SNP, which prompted us to genotype both polymorphisms. For each SNP, a three-factor multivariate analysis of variance (MANOVA) was computed for healthy volunteers and suicide attempters integrating the seven subscales of the State-Trait Angry Expression Inventory (State Anger, Trait Anger, Angry Temperament, Angry Reaction, Anger-In, Anger-Out, Anger Control), the two subscales Irritability and Assault of the Buss-Durkee Hostility Inventory, as well as the three factors: tryptophan hydroxylase genotype (UU + UL vs LL), gender (males, females) and diagnosis (healthy volunteers, suicide attempters) controlled for the covariates age and educational level (unfinished school, low, middle, high).…”

Section: Discussionmentioning

confidence: 99%

“…First studies on the A779C SNP found an excess of the 799C allele in impulsive suicide attempters, 12,13 whereas the association was inversed in the non-impulsive group. 13 Later studies found no association 14,15 or a marginal association 16 with the 799C allele. Most studies investigated a A218C SNP, which is in strong linkage disequilibrium with the A779C SNP.…”

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confidence: 94%

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Association of anger-related traits with SNPs in the TPH gene

et al. 2002

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Since both aggression-related traits and serotonergic activity are partially heritable and correlate inversely, variations in genes of the serotonergic system might then, to some extent, account for variations in aggression-related behavior. Tryptophan hydroxylase (TPH) is the rate limiting biosynthetic enzyme in the serotonin pathway and regulates levels of serotonin. Recently, a genetic variation in TPH has been associated with aggression and anger-related traits in volunteers. We investigated a sample of community-based healthy volunteers (n = 154) and suicide attempters (n = 86), a clinical population with a high risk for elevated impulsive aggression and related traits. The subjects were genotyped for a A218C and a A779C single nucleotide polymorphism (SNP) located in the TPH gene. All subjects were administered standard psychiatric interviews as well as self-report questionnaires for aggression, irritability and anger-related traits. For anger-related traits, a multivariate effect of the tryptophan hydroxylase genotype and an interaction effect for genotype and diagnosis was observed in healthy volunteers and suicide attempters after controlling for age and educational level. U-carriers in both groups showed higher scores for State Anger, Trait Anger and Angry Temperament. These findings support the hypothesis that the A218C and the A779C SNP in the TPH gene may be associated with anger-related traits in German samples. Molecular Psychiatry (2002) 7, 1023-1029. doi:10.1038/ sj.mp.4001128 Low cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) is regarded as a putative indicator for low serotonin turnover. 1 It is a relatively enduring trait which is partially genetically controlled as suggested by studies in humans, 2 and demonstrated in rhesus monkeys. 3,4 In these animals, low CSF 5-HIAA is associated with aggressiveness, low social affiliation, high-risk behavior, and premature mortality. [5][6][7] In humans, 5-HIAA in the CSF correlates inversely with various aggressive behaviors as demonstrated in healthy and psychiatric samples throughout the life span. Although there are some negative reports, taken together, the vast majority of findings suggest that lowered 5-HIAA is related to the vulnerability for aggressive behavior. 1,8 The tryptophan hydroxylase (TPH) gene encodes the rate limiting biosynthetic enzyme in the serotonin pathway, and regulates levels of serotonin. 9 Therefore, variations in the TPH gene could contribute to the predisposition to low serotonergic neurotransmission. A single nucleotide polymorphism (SNP) consisting of an A779C transversion 10 has been reported for the TPH gene, resulting in two alleles which are commonly addressed to as 'U' (upper) and 'L' (lower) respectively. In healthy volunteers, lower CSF 5-HIAA levels were found in men but not in women carrying the TPH U allele. 11 In contrast, in a small, behaviorally extreme, impulsive group of alcoholic violent offenders, Nielsen and colleagues 12 originally observed...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 94%

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Association of anger-related traits with SNPs in the TPH gene

et al. 2002

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“…Post-mortem analyses with DNA derived from suicide victims yielded negative results for 47 depressed Caucasians suicide victims, 54 35 depressed suicide victims of Canadian origin 55 and for 160 deceased males of Slavic origin. 56 Two groups investigated the TPH1 polymorphism in Japanese suicide victims, but both failed to demonstrate an association between suicide and the A-6526G and A218C polymorphism.…”

Section: The Tph1 Genementioning

confidence: 99%

“…56 Two groups investigated the TPH1 polymorphism in Japanese suicide victims, but both failed to demonstrate an association between suicide and the A-6526G and A218C polymorphism. 57,58 Also studies with Caucasians suicide attempters of different diagnostic categories yielded negative results between suicide attempts in unipolar and bipolar patients 54,59,60 or alcohol-dependent patients, 61 although some of the studies identified an association between the A218C polymorphism and the disorder in question. A case-control family-based study in Ashkenazi and non-Ashkenazi Jewish adolescents again revealed no significant allelic association with the A218C polymorphism.…”

Section: The Tph1 Genementioning

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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