Neumeister Alexander, Konstantinidis Anastasios, Stastny Juergen, Schwarz Markus J, Vitouch Oliver, Willeit Matthaus, Praschak-Rieder Nicole, Zach Johanna, de Zwaan Martina, Bondy Brigitta, Ackenheil Manfred, Kasper Siegfried
National Institutes of Health, NIMH, Mood and Anxiety Disorders Program, Bethesda, MD 20892-2670.
Arch Gen Psychiatry. 2002 Jul;59(7):613-20. doi: 10.1001/archpsyc.59.7.613.
Evidence suggests that serotonin transporter gene promoter polymorphism (5HTTLPR)-dependent low transcriptional activity of the human serotonin transporter gene may be a genetic susceptibility factor for depression. We studied the behavioral responses to tryptophan depletion (TD) in healthy women with and without a first-degree family history of depression and examined the relationship to 5HTTLPR alleles.
Twenty-four healthy women with a negative family history of depression and 21 women with a positive family history of depression were genotyped for the polymorphism of the 5HTTLPR and then entered a double-blind, placebo-controlled, randomized crossover TD study. The effects of these interventions were assessed with measures of depression and plasma tryptophan levels.
The TD induced a robust decrease of plasma tryptophan levels in all women irrespective of family history of depression or 5HTTLPR genotypes. The s/s genotype of the 5HTTLPR was associated with an increased risk of developing depressive symptoms during TD irrespective of family history. In contrast, individuals with the l/l genotype did not develop depressive symptoms, irrespective of family history. Finally, s/l subjects without family history showed a mood response that was intermediate between the s/s and l/l subjects, while s/l subjects with a family history of depression showed the same depressiogenic effect of TD as seen in the s/s subjects.
The results of the present study suggest that the s-allele of the 5HTTLPR and a positive family history of depression are additive risk factors for the development of depression during TD.
有证据表明,人类血清素转运体基因启动子多态性(5HTTLPR)依赖的低转录活性可能是抑郁症的一个遗传易感性因素。我们研究了有或无抑郁症一级家族史的健康女性对色氨酸耗竭(TD)的行为反应,并探讨了其与5HTTLPR等位基因的关系。
对24名抑郁症家族史阴性的健康女性和21名抑郁症家族史阳性的女性进行5HTTLPR多态性基因分型,然后进入一项双盲、安慰剂对照、随机交叉TD研究。通过抑郁量表和血浆色氨酸水平评估这些干预措施的效果。
无论抑郁症家族史或5HTTLPR基因型如何,TD均导致所有女性血浆色氨酸水平显著下降。5HTTLPR的s/s基因型与TD期间出现抑郁症状的风险增加相关,与家族史无关。相比之下,无论家族史如何,l/l基因型的个体均未出现抑郁症状。最后,无家族史的s/l受试者的情绪反应介于s/s和l/l受试者之间,而有抑郁症家族史的s/l受试者表现出与s/s受试者相同的TD致抑郁作用。
本研究结果表明,5HTTLPR的s等位基因和抑郁症阳性家族史是TD期间抑郁症发生的累加风险因素。