No effect of 5HTTLPR or BDNF Val66Met polymorphism on hippocampal morphology in major depression.
No effect of 5HTTLPR or BDNF Val66Met polymorphism on hippocampal morphology in major depression.
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DOI：
10.1111/j.1601-183x.2011.00714.x
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Fu CH
中科院分区：
文献类型：
--
作者：
Cole J;Weinberger DR;Mattay VS;Cheng X;Toga AW;Thompson PM;Powell-Smith G;Cohen-Woods S;Simmons A;McGuffin P;Fu CH
神经影像学研究表明海马体与重度抑郁症 (MDD) 的病因有关。影像遗传学研究调查了血清素转运蛋白相关多态性区域 (5HTTLPR) 和脑源性神经营养因子 (BDNF) Val66Met 多态性对健康个体和抑郁症 (MDD) 患者海马体的影响。然而，相互矛盾的结果导致关于 5HTTLPR 或 BDNF 对海马体积 (HCV) 影响的证据尚无定论。我们假设基于三维 (3D) 海马形状映射的分析方法可以提高阐明这些影响的灵敏度。磁共振成像数据是在 111 名健康个体和 84 名 MDD 患者的平行样本中收集的。进行手动海马分割，所得数据用于研究 5HTTLPR 和 BDNF Val66Met 基因型对每个样本内的 HCV 和 3D 形状的影响。通过颅内体积（ICV）归一化的海马体积显示，健康个体组中 5HTTLPR S 等位基因携带者和 L/L 纯合子之间或 BDNF Met 等位基因携带者和 Val/Val 纯合子之间没有显着差异。此外，尽管 BDNF Val66Met 与 ICV 之间存在相关性，但 MDD 患者中 5HTTLPR 双等位基因和三等基因分类之间或 BDNF Val66Met 基因型之间的标准化 HCV 没有显着差异。形状分析检测到分散的组间差异，但这些影响未能通过多重测试校正。在这项研究中，尽管样本量相对较大且方法敏感，但没有证据表明 5HTTLPR 或 BDNF Val66Met 对健康个体或 MDD 患者的海马形态有遗传影响。
Neuroimaging research implicates the hippocampus in the aetiology of major depressive disorder (MDD). Imaging genetics studies have investigated the influence of the serotonin transporter-linked polymorphic region (5HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on the hippocampus in healthy individuals and patients with depression (MDD). However, conflicting results have led to inconclusive evidence about the effect of 5HTTLPR or BDNF on hippocampal volume (HCV). We hypothesized that analysis methods based on three-dimensional (3D) hippocampal shape mapping could offer improved sensitivity to clarify these effects. Magnetic resonance imaging data were collected in parallel samples of 111 healthy individuals and 84 MDD patients. Manual hippocampal segmentation was conducted and the resulting data used to investigate the influence of 5HTTLPR and BDNF Val66Met genotypes on HCV and 3D shape within each sample. Hippocampal volume normalized by intracranial volume (ICV) showed no significant difference between 5HTTLPR S allele carriers and L/L homozygotes or between BDNF Met allele carriers and Val/Val homozygotes in the group of healthy individuals. Moreover, there was no significant difference in normalized HCV between 5HTTLPR diallelic and triallelic classifications or between the BDNF Val66Met genotypes in MDD patients, although there was a relationship between BDNF Val66Met and ICV. Shape analysis detected dispersed between-group differences, but these effects did not survive multiple testing correction. In this study, there was no evidence of a genetic effect for 5HTTLPR or BDNF Val66Met on hippocampal morphology in either healthy individuals or MDD patients despite the relatively large sample sizes and sensitive methodology.