No association between bipolar affective disorder and a serotonin receptor (5-HT2A) polymorphism

Mahieu, Boris; Souery, Daniel; Lipp, Olivier; Mendelbaum, Karine; Verheyen, Geert R.; Maertelaer, Viviane De; Broeckhoven, Christine Van; Mendlewicz, Julien

doi:10.1016/s0165-1781(97)03028-x

Cited by 44 publications

(23 citation statements)

References 16 publications

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“…This is in accordance with previous association studies between 5-HT2a and bipolar disorder [25,26] as well as between DRD2, DRD3 and DAT1 and bipolar disorder [27][28][29][30]. These results may indicate that in our Austrian sample, these polymorphisms are unlikely to play a major role in genetic susceptibility for bipolar disorder.…”

Section: Discussionsupporting

confidence: 93%

Association Studies of Candidate Genes in Bipolar Disorders

Heiden

Schüssler²,

Itzlinger³

et al. 2000

Neuropsychobiology

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The aim of the investigation was to test genes for predisposition to bipolar affective disorder. Therefore, we studied candidate genes in a sample of unrelated patients (n = 102) and healthy controls (n = 79) of Austrian origin, searching for a possible association between polymorphic DNA markers of 5 candidate genes (serotonin transporter, 5-HTT; serotonin 2a receptor, 5-HT2a; dopamine D2 receptor, DRD2; dopamine D3 receptor, DRD3; dopamine transporter, DAT1) and bipolar disorder. There was an association between allelic and genotypic frequencies of 5-HTT and affection status (p = 0.014 and p = 0.017, respectively). However, after correction for multiple comparisons (Bonferroni), these results did not remain significant. Nevertheless, the findings might suggest that alterations in the structure of 5-HTT are involved in the pathogenesis of bipolar disorder, which could have major implications in treatment. No association between 5-HT2a, DRD2, DRD3, DAT1 and bipolar disorder was found.

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Section: Discussionsupporting

confidence: 93%

Association Studies of Candidate Genes in Bipolar Disorders

Heiden

Schüssler²,

Itzlinger³

et al. 2000

Neuropsychobiology

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“…Our results confirm previous reports that genotype frequencies of 102T/C 5-HT 2A receptor gene polymorphism in mood disorders do not differ from healthy volunteers (Arranz et al, 1997;Bondy et al, 2000;Crawford et al, 2000;Mahieu et al, 1997;Minov et al, 2001;Tsai et al, 1999;Ono et al, 2001;Correa et al, 2002;Geijer et al, 2000). Nevertheless, we found an excess of the TC genotype in suicide attempters compared with nonattempters.…”

Section: Discussionsupporting

confidence: 91%

“…A more recent meta-analysis demonstrated a stronger association with schizophrenia in Caucasians compared with other ethnic groups (Abdolmaleky et al, 2004). No association of genotype or allele frequencies is found with suicide or mood disorders (Arranz et al, 1997;Bondy et al, 2000;Crawford et al, 2000;Mahieu et al, 1997;Minov et al, 2001;Tsai et al, 1999;Ono et al, 2001;Correa et al, 2002;Geijer et al, 2000). Turecki et al (2003) found that higher 5-HT 2A binding in the brain is associated with the T102C polymorphism in the 5-HT 2A gene independently of suicide, although others disagree (Hrdina and Du, 2001).…”

Section: Introductionmentioning

confidence: 99%

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

Khait

Huang

Zalsman

et al. 2004

Neuropsychopharmacol

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Serotonin 5-HT 2A receptor (5-HT 2A ) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive-impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive-impulsive traits has not been established. This study examines the possible association of the 5-HT 2A gene C102T polymorphism with the receptor binding kinetics, and clinical overt phenotypes. The study population included 63 healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history of suicide attempts. All were Caucasian. Platelet 5-HT 2A binding kinetics (B max and K D ) were assayed and adjusted for seasonal variation. All subjects were genotyped for the T102C polymorphism. Clinical phenotype was determined by structured clinical interview. The TT genotype was associated with higher B max in all subjects (F ¼ 3.53, df ¼ 2,211; p ¼ 0.03), controlling for diagnosis. Bonferroni-adjusted post hoc testing showed higher binding in the TT compared with TC genotype in the control group (F ¼ 7.56, df ¼ 2,60, p ¼ 0.001), but not in the mood-disordered subjects. No difference was found in genotype and allele distribution between the mood-disordered subjects, with and without suicide attempt history, and controls. B max was not related to a diagnosis of mood disorders.The TT genotype appears associated with higher platelet 5-HT 2A B max in the healthy population, but this genotypic effect appears absent in mood disorders and unrelated to psychopathology.

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“…Several authors have recently explored the possible implication of this gene in the origin of major depression and risk for suicide. Whereas results in major depression seem to discard a major role of HTR2A in the etiology of depressive disorder [Gutie Ârrez et al, 1995;Mahieu et al, 1997;Ohara et al, 1998], a signi®cant association between the 5-HT2A-C allele and suicidality has been reported [Du et al, 2000]. This association has not been replicated by other authors Crawford et al, 2000;Preuss et al, 2000].…”

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confidence: 98%

The 5‐HT_2A receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients

et al. 2001

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Several lines of evidence suggest that genetic factors constitute an important determinant of suicidal behavior. A significant association between the 5-HT(2A)-C allele and suicidality has recently been reported. The aim of this study was to investigate whether the proposed association between 5-HT(2A)-102T/C polymorphism and suicidality could be replicated in a larger and independent sample of Spanish patients with major depression. The 102T/C polymorphism of the 5-HT(2A) receptor gene was analyzed in 159 patients with major depression (DSM-IV criteria) and 164 unrelated and healthy controls using a case control design. All individuals were subjects of Spanish origin. Significant differences in allele (chi-square = 4.13, df = 1, P = 0.04) and genotype (chi-square = 6.19, df = 2, P = 0.04) distributions were found between non-suicide attempters and suicide attempters. Moreover, those patients carrying 5-HT(2A)-C allele had more than five times the risk for attempting suicide than noncarriers (OR = 5.50, 95% CI = 1.18-35.20, P = 0.01). Our results replicate the proposed association between 5HT(2A)-C allele and suicidality in major depression. Moreover, no overall associations are detected when patients with major depression and controls are compared for 102T/C frequencies, suggesting that the increased risk for suicidality conferred by 5-HT(2A)-C allele is primarily associated with suicidal behavior and not with the diagnosis of major depression itself.

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No association between bipolar affective disorder and a serotonin receptor (5-HT2A) polymorphism

Cited by 44 publications

References 16 publications

Association Studies of Candidate Genes in Bipolar Disorders

Association Studies of Candidate Genes in Bipolar Disorders

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

The 5‐HT_2A receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients

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No association between bipolar affective disorder and a serotonin receptor (5-HT2A) polymorphism

Cited by 44 publications

References 16 publications

Association Studies of Candidate Genes in Bipolar Disorders

Association Studies of Candidate Genes in Bipolar Disorders

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

The 5‐HT2A receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients

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The 5‐HT_2A receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients