title: The role of tyrosine hydroxylase gene variants in suicide attempt in schizophrenia.
abstract: Evidence has shown that attempted suicide in psychiatric disorders is a complex interplay of genes and environment. Noradrenergic dysfunction due to abnormalities in the tyrosine hydroxylase (TH) gene has been implicated in the pathogenesis of suicidal behavior in mood disorders. However, suicide is a leading cause of mortality in schizophrenia too. Recent evidence suggests that TH gene variants may also increase the risk of suicide attempts in schizophrenia patients, although the interaction with established clinical risk factors is unclear. This study aimed to identify TH gene variants conferring risk for suicide attempt in schizophrenia while accounting for the interaction between this gene and clinical risk factors. We performed analysis on four TH SNPs (rs11564717, rs11042950, rs2070762, rs689) and the common TCAT repeat (UniSTS:240639) for 234 schizophrenia patients (51 suicide attempters and 183 non-attempters). Clinical risk factors and ethnic stratification were included as covariates. Single marker analysis identified the SNP rs11564717 (p=0.042) and the TCAT(6) (p=0.004) as risk variants for suicide attempt. We also identified the haplotype A-A-A-G as a risk factor for suicide attempt (p=0.0025). In conclusion, our findings suggest that TH polymorphisms may contribute to the risk of attempted suicide in schizophrenia even after accounting for established clinical risk factors and ethnic stratification. Further larger scale studies are needed to confirm these findings and to understand the mechanisms underlying the role of TH gene variants in suicide attempt in schizophrenia.
authors.affiliation: Group for Suicide Studies, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Hu
authors.affiliation: Group for Suicide Studies, Centre for Addiction and Mental Health (CAMH), Toronto, Canada; Psychiatry Department, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, Malaysia.
authors.forename: Lai Fong
authors.initials: LF
authors.lastname: Chan
authors.affiliation: Group for Suicide Studies, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
authors.forename: Renan P
authors.initials: RP
authors.lastname: Souza
authors.affiliation: Group for Suicide Studies, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Tampakeras
authors.affiliation: Group for Suicide Studies, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.affiliation: Group for Suicide Studies, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
authors.forename: Clement
authors.initials: C
authors.lastname: Zai
authors.affiliation: Group for Suicide Studies, Centre for Addiction and Mental Health (CAMH), Toronto, Canada. Electronic address: vincenzo_deluca@camh.net.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
mesh_terms: D000328:Adult; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics*; D012565:Schizophrenic Psychology; D013406:Suicide, Attempted / Q000523:psychology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000502:physiology
chemical_list: D014446:Tyrosine 3-Monooxygenase
keywords: Clinical risk factors; Schizophrenia; Suicide attempt; Tyrosine hydroxylase gene