Increased risk of suicide attempt in mood disorders and TPH1 genotype

• Published in: Journal of affective disorders Vol. 115; no. 3; pp. 331 - 338
• Main Authors: Galfalvy, Hanga, Huang, Yung-yu, Oquendo, Maria A., Currier, Dianne, Mann, J. John
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.06.2009; Elsevier
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Affective disorders; Aged; Biological and medical sciences; Bipolar Disorder - complications; Bipolar Disorder - genetics; Black or African American - statistics & numerical data; Depression; Depressive Disorder, Major - complications; Depressive Disorder, Major - genetics; Ethnicity; Female; Genes; Genetic Predisposition to Disease; Genetic susceptibility; Haplotype analysis; Haplotypes; Hispanic or Latino - statistics & numerical data; Homovanillic Acid - cerebrospinal fluid; Humans; Hydroxyindoleacetic Acid - cerebrospinal fluid; Major depressive episode; Male; Medical sciences; Methoxyhydroxyphenylglycol - cerebrospinal fluid; Middle Aged; Mood disorders; Mood Disorders - cerebrospinal fluid; Mood Disorders - complications; Mood Disorders - ethnology; Mood Disorders - genetics; New York; Polymorphism, Single Nucleotide; Prediction; Predictors; Prospective Studies; Psychiatric/Mental Health; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Risk Factors; Sex Factors; Suicidal behaviour; Suicide; Suicide attempt; Suicide, Attempted - ethnology; Suicide, Attempted - psychology; Tryptophan Hydroxylase - genetics; Tryptophan Hydroxylase - metabolism; White People - statistics & numerical data; Young Adult; New York; Major depressive episode; Haplotype analysis; Prediction; Suicide attempt; Mood disorder; Risk factor; Genetics; Depression; Genotype; Genetic determinism; Haplotype
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2008.09.019

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. 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. 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. The TPH1 gene is likely one of several genes associated with suicidal behavior. Power to detect differential genotype effects by ethnicity is low. Polymorphisms of TPH1 may assist in identifying a subgroup of mood disorder patients that is at higher risk for suicidal behavior.