Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders

A Multicenter Association Study

Daniel Souery, Sophie Van Gestel, Isabelle Massat, Sylvie Blairy, Rolf Adolfsson, Douglas Blackwood, Jurgen Del-Favero, Dimitris Dikeos, Miro Jakovljevic, Radka Kaneva, Enrico Lattuada, Bernard Lerer, Roberta Lilli, Vihbra Milanova, Walter Muir, Markus Nöthen, Lilijana Oruc, George Papadimitriou, Peter Propping, Thomas Schulze & 7 others Alessandro Serretti, Baruch Shapira, Enrico Smeraldi, Costas Stefanis, Marian Thomson, Christine Van Broeckhoven, Julien Mendlewicz

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Background: Being the rate-limiting enzyme in the biosynthesis of serotonin, the tryptophan hydroxylase gene (TPH) has been considered a possible candidate gene in bipolar and unipolar affective disorders (BPAD and UPAD). Several studies have investigated the possible role of TPH polymorphisms in affective disorders and suicidal behavior. Methods: The TPH A218C polymorphism has been investigated in 927 patients (527 BPAD and 400 UPAD) and their matched healthy control subjects collected within the European Collaborative Project on Affective Disorders. Results: No difference of genotype distribution or allele distribution was found in BPAD or UPAD. No statistically significant difference was observed for allele frequency and genotypes counts. In a genotype per genotype analysis in UPAD patients with a personal history of suicide attempt, the frequency of the C-C genotype (homozygosity for the short allele) was lower in UPAD patients (24%) than in control subjects (43%) (χ2 = 4.67, p = .03). There was no difference in allele or genotype frequency between patients presenting violent suicidal behavior (n = 48) and their matched control subjects. Conclusions: We failed to detect an association between the A218C polymorphism of the TPH gene and BPAD and UPAD in a large European sample. Homozygosity for the short allele is significantly less frequent in a subgroup of UPAD patients with a history of suicide attempt than in control subjects.

Original languageEnglish
Pages (from-to)405-409
Number of pages5
JournalBiological Psychiatry
Volume49
Issue number5
DOIs
Publication statusPublished - Mar 1 2001

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Tryptophan Hydroxylase
Mood Disorders
Bipolar Disorder
Multicenter Studies
Genotype
Alleles
Genes
Suicide
Gene Frequency
Serotonin
Healthy Volunteers
Enzymes

Keywords

  • Association study
  • Bipolar affective disorders
  • Linkage disequilibrium
  • Suicide
  • Tryptophan hydroxylase polymorphism

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders : A Multicenter Association Study. / Souery, Daniel; Van Gestel, Sophie; Massat, Isabelle; Blairy, Sylvie; Adolfsson, Rolf; Blackwood, Douglas; Del-Favero, Jurgen; Dikeos, Dimitris; Jakovljevic, Miro; Kaneva, Radka; Lattuada, Enrico; Lerer, Bernard; Lilli, Roberta; Milanova, Vihbra; Muir, Walter; Nöthen, Markus; Oruc, Lilijana; Papadimitriou, George; Propping, Peter; Schulze, Thomas; Serretti, Alessandro; Shapira, Baruch; Smeraldi, Enrico; Stefanis, Costas; Thomson, Marian; Van Broeckhoven, Christine; Mendlewicz, Julien.

In: Biological Psychiatry, Vol. 49, No. 5, 01.03.2001, p. 405-409.

Research output: Contribution to journalArticle

Souery, D, Van Gestel, S, Massat, I, Blairy, S, Adolfsson, R, Blackwood, D, Del-Favero, J, Dikeos, D, Jakovljevic, M, Kaneva, R, Lattuada, E, Lerer, B, Lilli, R, Milanova, V, Muir, W, Nöthen, M, Oruc, L, Papadimitriou, G, Propping, P, Schulze, T, Serretti, A, Shapira, B, Smeraldi, E, Stefanis, C, Thomson, M, Van Broeckhoven, C & Mendlewicz, J 2001, 'Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: A Multicenter Association Study', Biological Psychiatry, vol. 49, no. 5, pp. 405-409. https://doi.org/10.1016/S0006-3223(00)01043-X
Souery, Daniel ; Van Gestel, Sophie ; Massat, Isabelle ; Blairy, Sylvie ; Adolfsson, Rolf ; Blackwood, Douglas ; Del-Favero, Jurgen ; Dikeos, Dimitris ; Jakovljevic, Miro ; Kaneva, Radka ; Lattuada, Enrico ; Lerer, Bernard ; Lilli, Roberta ; Milanova, Vihbra ; Muir, Walter ; Nöthen, Markus ; Oruc, Lilijana ; Papadimitriou, George ; Propping, Peter ; Schulze, Thomas ; Serretti, Alessandro ; Shapira, Baruch ; Smeraldi, Enrico ; Stefanis, Costas ; Thomson, Marian ; Van Broeckhoven, Christine ; Mendlewicz, Julien. / Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders : A Multicenter Association Study. In: Biological Psychiatry. 2001 ; Vol. 49, No. 5. pp. 405-409.
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T1 - Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders

T2 - A Multicenter Association Study

AU - Souery, Daniel

AU - Van Gestel, Sophie

AU - Massat, Isabelle

AU - Blairy, Sylvie

AU - Adolfsson, Rolf

AU - Blackwood, Douglas

AU - Del-Favero, Jurgen

AU - Dikeos, Dimitris

AU - Jakovljevic, Miro

AU - Kaneva, Radka

AU - Lattuada, Enrico

AU - Lerer, Bernard

AU - Lilli, Roberta

AU - Milanova, Vihbra

AU - Muir, Walter

AU - Nöthen, Markus

AU - Oruc, Lilijana

AU - Papadimitriou, George

AU - Propping, Peter

AU - Schulze, Thomas

AU - Serretti, Alessandro

AU - Shapira, Baruch

AU - Smeraldi, Enrico

AU - Stefanis, Costas

AU - Thomson, Marian

AU - Van Broeckhoven, Christine

AU - Mendlewicz, Julien

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N2 - Background: Being the rate-limiting enzyme in the biosynthesis of serotonin, the tryptophan hydroxylase gene (TPH) has been considered a possible candidate gene in bipolar and unipolar affective disorders (BPAD and UPAD). Several studies have investigated the possible role of TPH polymorphisms in affective disorders and suicidal behavior. Methods: The TPH A218C polymorphism has been investigated in 927 patients (527 BPAD and 400 UPAD) and their matched healthy control subjects collected within the European Collaborative Project on Affective Disorders. Results: No difference of genotype distribution or allele distribution was found in BPAD or UPAD. No statistically significant difference was observed for allele frequency and genotypes counts. In a genotype per genotype analysis in UPAD patients with a personal history of suicide attempt, the frequency of the C-C genotype (homozygosity for the short allele) was lower in UPAD patients (24%) than in control subjects (43%) (χ2 = 4.67, p = .03). There was no difference in allele or genotype frequency between patients presenting violent suicidal behavior (n = 48) and their matched control subjects. Conclusions: We failed to detect an association between the A218C polymorphism of the TPH gene and BPAD and UPAD in a large European sample. Homozygosity for the short allele is significantly less frequent in a subgroup of UPAD patients with a history of suicide attempt than in control subjects.

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