Increased risk of suicide attempt in mood disorders and TPH1 genotype.
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.


CONCLUSIONS
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.
Galfalvy
Hanga
H
Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University,; and New York State Psychiatric Institute, New York, NY 10032, USA. hcg2002@columbia.edu
Huang
Yung-Yu
YY
Oquendo
Maria A
MA
Currier
Dianne
D
Mann
J John
JJ
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D000368:Aged; D001714:Bipolar Disorder / Q000150:complications / Q000235:genetics; D003865:Major Depressive Disorder / Q000150:complications / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D019964:Mood Disorders / Q000134:cerebrospinal fluid / Q000150:complications* / Q000208:ethnology / Q000235:genetics*; D009518:New York; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D013406:Suicide, Attempted / Q000208:ethnology / Q000523:psychology*; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000706:statistics & numerical data; D055815:Young Adult
D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase; D006719:Homovanillic Acid