The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder - Preliminary findings

被引:123
作者
Mundo, E [1 ]
Walker, M [1 ]
Cate, T [1 ]
Macciardi, F [1 ]
Kennedy, JL [1 ]
机构
[1] Univ Toronto, Neurogenet Sect, Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada
关键词
D O I
10.1001/archpsyc.58.6.539
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Background: II-he occurrence of mania during antidepressant treatment is a key issue in the clinical management of bipolar disorder (BP). The serotonin transporter (5-HTT) is the selective site of action of most proserotonergic compounds used to treat bipolar depression. The 5-HTT gene (SLC6A4) has 2 known polymorphisms. The aim of this study was to investigate the role of the SLC6A4 variants in the pathogenesis of antidepressant-induced mania in BP. Methods: Twenty-seven patients with a DSM-IV diagnosis of BP I or II, with at least 1 manic or hypomanic episode induced by treatment with proserotonergic antidepressants (IM+ group), were compared with 29 unrelated, matched patients with a diagnosis of BP I or II, who had been exposed to proserotonergic antidepressants without development of manic or hypomanic symptoms (IM- group). The 2 known polymorphisms of the SLC6A4 were genotyped, and allelic and genotypic association analyses were performed. Results: With respect to the polymorphism in the promoter region (5HTTLPR), IM+ patients had an excess of the short allele (n=34 [63%]) compared with IM- patients (n=17 [29%]) (chi (2)(1), 12.77; P < .001). The genotypic association analysis showed a higher rate of homozygosity for the short variant in the IM+ group (n=10 [37%]) than in the IM- group (n=2 [7%]) and a lower rate of homozygosity for the long variant in the IM+ group (n = 3 [11%]) compared with the IM- group (n=14 [48%]) (chi (2)(2), 12.43; P=.002). No associations were found for the polymorphism involving a variable number of tandem repeats. Conclusion: If these results are replicated, the 5HTTLPR polymorphism may become an important predictor of abnormal response to medication in patients with BP.
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页码:539 / 544
页数:6
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