Association Study of GABRG2 Polymorphisms with Suicidal Behaviour in Schizophrenia Patients with Alcohol Use Disorder

被引:13
作者
Zai, Clement C. [1 ,2 ]
Zai, Gwyneth C. [1 ,2 ,3 ]
Tiwari, Arun K. [1 ]
Manchia, Mirko [4 ,5 ,6 ]
de Luca, Vincenzo [1 ,2 ]
Shaikh, Sajid A. [1 ]
Strauss, John [1 ]
Kennedy, James L. [1 ,2 ,3 ]
机构
[1] Univ Toronto, Ctr Addict & Mental Hlth, Neurosci Res Dept, Neurogenet Sect, Toronto, ON, Canada
[2] Univ Toronto, Dept Psychiat, Toronto, ON, Canada
[3] Univ Toronto, Inst Med Sci, Toronto, ON, Canada
[4] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada
[5] Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada
[6] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy
关键词
Schizophrenia; Suicide specifier. Alcohol dependence; GABA(A) gamma(2) GABRG2; Genetics; GABA(A) RECEPTOR; SPLICE VARIANT; ENHANCED ANXIETY; GENE-EXPRESSION; GAMMA-2; SUBUNIT; BENZODIAZEPINES; SENSITIVITY; ETHANOL; RISK; MICE;
D O I
10.1159/000358839
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Schizophrenia is a severe neuropsychiatric disorder where the role of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, has been implicated in its aetiopathophysiology. Several genes coding for GABA(A) subunits, including the GABRG2 gene that encodes the gamma(2) subunit, are clustered at 5q31-q35, a chromosomal region that is associated with schizophrenia in genonne scan studies. We recently reported GABRG2 to be associated with schizophrenia in our case-control and family samples. Methods: We tested eight single-nucleotide polymorphisms spanning the GABRG2 gene for an association with suicidal behaviour in our schizophrenia sample of European ancestry (n = 197), taking into account history of alcohol abuse or dependence. Results: We found the haplotypes of the rs183294 and rs209356 markers to be significantly associated with history of suicide attempt (p < 0.01) as well as suicide specifier scores (p < 0.05). The association appeared to be originating in patients with a history of alcohol dependence or abuse. Conclusions: Taken together, the results of the present study suggest that GABRG2 may be involved in suicidal behaviour in schizophrenia patients with alcohol dependence or abuse, but replications are required. These results may help in the discovery of novel treatments for alcoholism and/or prevention of suicide. (C) 2014 S. Karger AG, Basel
引用
收藏
页码:154 / 158
页数:5
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