血清素转运体基因多态性与氟西汀治疗的不良反应
Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment.
作者信息
Perlis Roy H, Mischoulon David, Smoller Jordan W, Wan Yu-Jui Yvonne, Lamon-Fava Stefania, Lin Keh-Ming, Rosenbaum Jerrold F, Fava Maurizio
机构信息
Department of Psychiatry, Massachusetts General Hospital, Boston 02114, USA.
出版信息
Biol Psychiatry. 2003 Nov 1;54(9):879-83. doi: 10.1016/s0006-3223(03)00424-4.
BACKGROUND
The short (S) allele of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been associated with poorer antidepressant response in major depressive disorder (MDD) and with antidepressant-induced mania. This study investigated a possible association with treatment-emergent insomnia or agitation.
METHODS
Thirty-six outpatients with MDD were genotyped at 5HTTLPR and treated with open-label fluoxetine up to 60 mg/day. Treatment-emergent adverse effects were assessed at each study visit.
RESULTS
Of nine subjects homozygous for the "S" allele, seven (78%) developed new or worsening insomnia, versus 6 of 27 (22%) non-"S"-homozygous subjects (Fisher's exact p =.005). Similarly, six of nine subjects homozygous for the "S" allele (67%) developed agitation, versus 2 of 27 (7%) of non-"S"-homozygous subjects (Fisher's exact p =.001).
CONCLUSIONS
The "S" allele of the 5HTTLPR may identify patients at risk for developing insomnia or agitation with fluoxetine treatment. This preliminary result requires confirmation in larger samples.
背景
血清素转运体基因连锁多态性区域（5HTTLPR）的短（S）等位基因与重度抑郁症（MDD）患者较差的抗抑郁反应以及抗抑郁药诱发的躁狂症有关。本研究调查了其与治疗中出现的失眠或激越之间可能存在的关联。
方法
对36例MDD门诊患者进行5HTTLPR基因分型，并用每日剂量高达60mg的开放标签氟西汀进行治疗。在每次研究访视时评估治疗中出现的不良反应。
结果
在9例“S”等位基因纯合的受试者中，7例（78%）出现了新的或加重的失眠，相比之下，27例非“S”等位基因纯合受试者中有6例（22%）出现这种情况（Fisher精确检验p = 0.005）。同样，9例“S”等位基因纯合受试者中有6例（67%）出现激越，相比之下，27例非“S”等位基因纯合受试者中有2例（7%）出现激越（Fisher精确检验p = 0.001）。
结论
5HTTLPR的“S”等位基因可能识别出接受氟西汀治疗时出现失眠或激越风险的患者。这一初步结果需要在更大样本中得到证实。
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