Association Study of Genotype by Depressive Response during Tryptophan Depletion in Subjects Recovered from Major Depression.
Association Study of Genotype by Depressive Response during Tryptophan Depletion in Subjects Recovered from Major Depression.
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DOI：
10.1159/000439114
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Delgado PL
中科院分区：
文献类型：
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作者：
Moreno FA;Erickson RP;Garriock HA;Gelernter J;Mintz J;Oas-Terpstra J;Davies MA;Delgado PL
对急性色氨酸（TRP）耗竭（ATD）的短暂和可逆的情绪反应正在被研究作为被认为有重度抑郁症（MD）风险的受试者的一个特质标志。对64名有MD个人和家族史的受试者（54名欧洲裔美国人和10名其他种族）进行ATD治疗。他们的病情已得到缓解，并且至少三个月没有服药。受试者在随机分配、双盲交叉设计中接受活性和假治疗。他们进行了基因分型的降钙素相关的候选基因，情绪反应量化与汉密尔顿抑郁量表（HDRS）。数据进行了分析，使用泊松回归与重复测量和潜在的轨迹模型。与假手术对照组相比，主动ATD引起中度抑郁变化，显示出显著的测试条件（χ2=5.14，df=1，p=0.023）和时间（χ2=12.22，df=3，p=0.007）的主效应，但时间和测试条件之间没有显著的相互作用。潜在轨迹分析揭示了两组，确定为耗竭反应者和非反应者。HTR 2A rs6313 CC基因型患者在ATD期间的HDRS评分显著较高（χ2=11.72，df=1，p=.0006）。ATD可能有助于识别MD的生物学亚型。这些数据与影像学报告显示ATD表型中5-HT 2A受体功能一致。
The brief and reversible mood response to acute tryptophan (TRP) depletion (ATD) is being studied as a trait marker in subjects considered at risk for major depression (MD). ATD was administered to 64 subjects (54 European-Americans, and10 from other races) with personal and family history of MD. They were in remission and had been medication-free for at least three months. Subjects received an active and sham condition in a random assignment, double-blind crossover design. They were genotyped for serotonin-related candidate genes, and mood response was quantified with the Hamilton Depression Rating Scale (HDRS). Data were analyzed using Poisson regression with repeated measures and latent trajectory models. Compared to the sham control, active ATD caused modest depressive changes showing significant main effects of test condition (χ2=5.14, df=1, p=0.023) and time (χ2=12.22, df=3, p=0.007), but no significant interaction of time and test condition. Latent trajectory analysis revealed two groups, identified as depletion responders and non-responders. Those with the HTR2A rs6313 CC genotype had significantly higher HDRS scores during ATD (χ2=11.72, df=1, p=.0006). ATD may help the identification of biological subtypes of MD. These data are consistent with imaging reports implicating 5-HT2A receptor function in ATD phenotypes.