Search for association between suicide attempt and serotonergic polymorphisms

Geijer, Thomas; Frisch, Amos; Ml, Persson; Wasserman, Danuta; Rockah, Rivka; Michaelovsky, Elena; Apter, Alan; Jönsson, Erik G.; Mm, Nöthen; Weizman, Abraham

doi:10.1097/00041444-200010010-00004

Cited by 87 publications

(49 citation statements)

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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%

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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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Section: Discussionsupporting

confidence: 91%

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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“…A nonsignificant protective effect of the S allele was observed among Spaniards [109] and Germans [141,142]. Five studies of whites [143][144][145][146][147] found no substantial relationships between the 5-HTTLPR genotype and major depressive disorder. In contrast, seven Caucasian [148][149][150][151][152][153][154] and one non-Ashkenazi Jewish [144] studies found that the SS genotype was associated with a modest increase in risk of depression.…”

Section: Major Depressive Disorder and 5-httlpr Polymorphismmentioning

confidence: 92%

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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“…There are seven published studies relating the 5-HTT genotype with suicide in specific diagnostic groups. Three studies: one on completed suicide (Mann et al 2000), one on attempted suicide (Geijer et al 2000), and one on subjects believed to have high risk (Russ et al 2000) did not show any association. One very small study on completed suicide in depression showed an increase of L subjects (Du et al 1999).…”

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confidence: 86%

A Gender-Specific Association between the Serotonin Transporter Gene and Suicide Attempts

Baca‐García

Vaquero

Díaz-Sastre

et al. 2002

Neuropsychopharmacology

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This pilot study tested the gender-specificity of the association between suicide attempts and a polymorphism in the promoter area of the serotonin transporter with two allelic variants, a long (1) variant and a short (s) variant. In aSuicide attempts, in more than 90% of the cases, are associated with mental disorders. Vulnerability to suicide is probably best understood in the context of Mann's model of stress-diathesis (Mann et al. 1999). Low brain serotonergic function appears to be undeniably related to suicidal behavior across different psychiatric diagnoses and within specific psychiatric diagnoses (Mann et al. 1999).Growing evidence indicates that genetic factors contribute to suicide risk. Moreover, familial and adoption studies suggest that it appears to be transmitted as a trait independent of Axis I and II disorders. A recent study suggested that genetic factors account for 45% of the variance in suicidal behavior, and more importantly can be detected after correcting for psychiatric diagnosis, traumatic events, personality traits, and religious affiliations (Statham et al. 1998).The serotonin transporter (5-HTT) gene is one of the major genes known to influence serotonergic transmission. It was mapped to the chromosome 17q11.1-q12. In the promoter area, there are two allelic variants, a long (l) variant and a short (s) variant. In vitro studies show that the "l" allele has two to three times higher basal transcriptional activity.

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Search for association between suicide attempt and serotonergic polymorphisms

Cited by 87 publications

References 0 publications

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

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

Molecular epidemiology of major depressive disorder

A Gender-Specific Association between the Serotonin Transporter Gene and Suicide Attempts

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