Borg Jacqueline, Henningsson Susanne, Saijo Tomoyuki, Inoue Makoto, Bah Jessica, Westberg Lars, Lundberg Johan, Jovanovic Hristina, Andrée Bengt, Nordstrom Anna-Lena, Halldin Christer, Eriksson Elias, Farde Lars
Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry and Stockholm Brain Institute, Stockholm, Sweden.
Int J Neuropsychopharmacol. 2009 Jul;12(6):783-92. doi: 10.1017/S1461145708009759. Epub 2009 Jan 6.
The human serotonin transporter (5-HTT) gene is one of the most extensively studied in psychiatry. A functional polymorphism in the promoter region of the 5-HTT gene (5-HTTLPR) has been associated with several psychiatric disorders as well as anxiety-related personality traits. In search of a mechanistic understanding of the functional implications of 5-HTTLPR, the influence of this polymorphism on regional 5-HT1A receptor density has previously been examined in two positron emission tomography (PET) studies in humans, yielding, however, contradictory results. In the present study, 54 control subjects were examined with [11C]WAY 100635 PET and a battery of cognitive tests. Regional binding potential (BP) of [11C]WAY 100635 to 5-HT1A receptor was calculated for the dorsal raphe nuclei, the hippocampus, the anterior cingulate, the insula, the temporal cortex and the frontal cortex. The influence of 5-HTTLPR genotype on regional 5-HT1A BP and cognitive performance was investigated. No differences in 5-HT1A receptor density between carriers and non-carriers of the S allele were found. Thus, we could not replicate any of the previously reported associations between 5-HTTLPR and 5-HT1A density. There was, however, a highly significant association between 5-HTTLPR genotype and performance in Wisconsin Card Sorting Test; carriers of the S allele had a superior performance compared to the LL carriers. These observations suggest that functional implications of the 5-HTTLPR polymorphism are not likely to be mediated by differences in 5-HT1A expression levels and that other biomarkers must be considered for future investigations at phenotype level.
人类血清素转运体（5-HTT）基因是精神病学领域研究最为广泛的基因之一。5-HTT基因启动子区域的一个功能性多态性（5-HTTLPR）与多种精神疾病以及焦虑相关的人格特质有关。为了深入了解5-HTTLPR功能影响的机制，此前已有两项针对人类的正电子发射断层扫描（PET）研究检测了该多态性对区域5-HT1A受体密度的影响，但结果相互矛盾。在本研究中，对54名对照受试者进行了[11C]WAY 100635 PET检查和一系列认知测试。计算了[11C]WAY 100635与背侧中缝核、海马体、前扣带回、脑岛、颞叶皮质和额叶皮质中5-HT1A受体的区域结合潜能（BP）。研究了5-HTTLPR基因型对区域5-HT1A BP和认知表现的影响。未发现S等位基因携带者与非携带者之间5-HT1A受体密度存在差异。因此，我们无法重复此前报道的5-HTTLPR与5-HT1A密度之间的任何关联。然而，5-HTTLPR基因型与威斯康星卡片分类测试的表现之间存在高度显著的关联；S等位基因携带者的表现优于LL携带者。这些观察结果表明，5-HTTLPR多态性的功能影响不太可能由5-HT1A表达水平的差异介导，未来在表型水平的研究必须考虑其他生物标志物。
