Increased risk of suicide attempt in mood disorders and TPH1 genotype

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• 作者：Hanga Galfalvy ; Yung-yu Huang ; Maria A. Oquendo ; Dianne Currier ; J. John Mann
• 关键词：Suicide attempt ; Prediction ; Major depressive episode ; Haplotype analysis
• 刊名：Journal of Affective Disorders
• 出版年：2009
• 出版时间：June 2009
• 年：2009
• 卷：115
• 期：3
• 页码：331-338
• 全文大小：227 K

文摘

Background

The tryptophan hydroxylase 1 (TPH1) gene is reported to be associated with suicidal behavior. This has not been confirmed by prospective studies of suicide and clinical or biological mediators of this genetic risk have not been identified.

Methods

343 subjects (Caucasian, African-American, Hispanic) presenting with a Major Depressive Episode were genotyped for polymorphisms A218C in intron 7 and A-6526G in the promoter region of TPH1, and monitored for suicide attempts for up to one year. Clinical correlates of suicidal behavior and CSF-HIAA, HVA and MHPG levels were explored as possible mediators of genetic risk. Analyses were adjusted for ethnicity.

Results

The AA genotype on intron 7 and the AA genotype on the promoter (both more prevalent in Caucasians) predicted suicide attempts during the 1 year follow-up, and were associated with past attempts of high medical lethality, regardless of ethnicity. The intron 7 genotype was associated with fewer reported reasons for living, and lower impulsivity. Haplotype analysis indicated significant increase in risk of suicide attempts for subjects with four risk alleles. TPH1 genotype was not associated with CSF metabolite levels.

Limitations

The TPH1 gene is likely one of several genes associated with suicidal behavior. Power to detect differential genotype effects by ethnicity is low.

Conclusions

Polymorphisms of TPH1 may assist in identifying a subgroup of mood disorder patients that is at higher risk for suicidal behavior.