Serotonin transporter genotype and depressive phenotype determination by discriminant analysis of glucose metabolism under acute tryptophan depletion.
Serotonin transporter genotype and depressive phenotype determination by discriminant analysis of glucose metabolism under acute tryptophan depletion.
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DOI：
10.1016/j.neuroimage.2008.07.040
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发表时间：
2008-12
期刊：
影响因子：
5.7
通讯作者：
Drevets WC
中科院分区：
文献类型：
--
作者：
Nugent AC;Neumeister A;Goldman D;Herscovitch P;Charney DS;Drevets WC
急性色氨酸耗竭（ATD）可导致中枢5-羟色胺传递的短暂减少，并在一些未用药的缓解型抑郁症（MDD）受试者中诱发抑郁情绪。5-HT转运蛋白启动子区长度多态性（5-HTTLPR）已被证明会影响ATD的行为和代谢反应，以及在应激背景下发生MDD的风险。本研究采用18FDG-PET研究5-HTTLPR基因型、对ATD的神经生理学反应和诊断表型（健康对照受试者与MDD受试者，通过对ATD的抑郁反应进行区分）之间的关系。对未用药的MDD缓解受试者和健康对照者进行5-HTTLPR多态性长（l）和短（s）等位基因的基因分型，并将其分为三种基因型之一。在两个不同的场合，受试者接受安慰剂或氨基酸混合物，旨在消耗血浆色氨酸，然后进行18FDG-PET扫描。对抑郁症状进行评定以确定诊断表型。使用脑区域代谢数据进行描述性和预测性判别分析，根据表型和基因型进行分类。总体而言，79%的病例按基因型正确分类，85%按表型正确分类。在留一法交叉验证中，72%的受试者被正确分类为携带s等位基因，79%的受试者被正确分类为初步诊断。分类结果的稳健性表明，对ATD的代谢反应的大部分差异是由基因型和表型类别造成的。
Acute tryptophan depletion (ATD) putatively results in a transient reduction in central serotonin transmission, and induces depressed mood in some un-medicated subjects with remitted major depressive disorder (MDD). The 5-HT transporter promoter region length polymorphism (5-HTTLPR) has been shown to influence behavioral and metabolic responses to ATD, as well as the risk for developing MDD within the context of stress. The current study investigates the relationships between 5-HTTLPR genotype, neurophysiologic response to ATD, and diagnostic phenotype (healthy control subjects versus MDD subjects differentiated by their depressive response to ATD) using 18FDG-PET. Un-medicated subjects with remitted MDD and healthy controls were genotyped for the long (l) and short (s) alleles of the 5-HTTLPR polymorphism and categorized into one of three genotypes. On two separate occasions, subjects received either a placebo or an amino acid mixture designed to deplete plasma tryptophan, followed by 18FDG-PET scanning. Depressive symptoms were rated to determine the diagnostic phenotype. Descriptive and predictive discriminant analyses were performed using brain regional metabolic data to classify according to phenotype and genotype. Overall, 79% of the cases were classified correctly by genotype, and 85% were classified correctly by phenotype. In a leave-one-out cross-validation, 72% of the subjects were classified correctly as carrying an s-allele, and 79% of the subjects were classified correctly by primary diagnosis. The robust nature of the classification results indicates that much of the variance in metabolic response to ATD is accounted for by genotypic and phenotypic category.
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影响因子：
4.3
作者：
BAUMANN, P
通讯作者：
BAUMANN, P
影响因子：
3.7
作者：
COSTANZA, MC;AFIFI, AA
通讯作者：
AFIFI, AA
影响因子：
5.6
作者：
Drevets, WC;Bogers, W;Raichle, ME
通讯作者：
Raichle, ME
影响因子：
17.7
作者：
Coryell, W;Nopoulos, P;Andreasen, NC
通讯作者：
Andreasen, NC
未服药的重度抑郁症缓解期患者和健康人对儿茶酚胺消耗的神经反应
影响因子：
--
作者：
Hasler, Gregor;Fromm, Stephen;Drevets, Wayne C.
通讯作者：
Drevets, Wayne C.