DEVELOPMENTAL NEUROMORPHOMETRY IN YOUNG DEPRESSED TWINS

描述：早发性重度抑郁障碍(MDD)具有高度的遗传性 并与前额叶-边缘-纹状体回路的结构变化有关 结构。在患有早发性MDD的年轻成年女性中，研究人员 亚膝前额叶皮质(SgPFC)的结构差异 还有杏仁核。具体地说，我们和其他人已经证明了 左侧sgPFC和右侧杏仁核。他们的初步研究提供了证据 基因和环境影响的贡献不同于 这两个地区。在最近对MDD不协调的同卵双胞胎的研究中， 研究人员已经证明，1)MDD的左侧sgPFC容量减少是 与未受影响的双胞胎相比，患有MDD的双胞胎中始终存在 同卵双胞胎和2)右侧杏仁核体积缩小和正常杏仁核丢失 这两个双胞胎都表现出不对称。因此，他们目前有证据表明 至少两种类型的发现：疾病中存在的结构性变化 双胞胎(左侧sgPFC减少)和高危双胞胎中存在的变化 (杏仁核)。他们假设，这些结构性差异可能是 神经发育起源的，继发于环境或遗传因素的， 分别进行了分析。另一种假设是，这些变化可能是次要的。 这是一种神经退行性或“疤痕”现象。 与神经发育假说有关，他们最近证明 8-21岁正常儿童sgPFC容量与年龄相关的显著增加 穿着横截面设计的女孩。调查人员提出了一项研究检查 利用高分辨率进行流行病学确诊的双胞胎样本 MRI以检查四个相互关联的目标：1)量化 患有MDD的年轻女性的前额叶-边缘环路神经形态测量；2)至 描述神经发育或神经退行性改变的模式 这些电路采用前瞻性的纵向设计；3)通过 双胞胎遗传模型加性遗传或环境因素的贡献 对观察到的结构差异的影响；以及4)增加 通过使用自动皮质进行神经形态特征的表征 提取方法和高维流体翘曲以精确 描绘受试者群体之间和整个发育阶段的形状变化 时间段。这对双胞胎受试者来自一个庞大的 在密苏里州出生的女性双胞胎的流行病学确认样本。这个 对双胞胎人口的调查将允许直接估计 遗传和环境对结构变化和发育的贡献 纵向上注意到的变化。与前沿遗传建模相结合 自动图像分析和更新的复杂形状分析提供了 独特的资源星座，将允许进行强大的探索 上述假设中的一个。

DESCRIPTION: Early onset major depressive disorder (MDD) is highly heritable and associated with structural changes in prefrontal-limbic-striatal circuit structures. In young adult females with early onset MDD, the investigators have demonstrated structural differences in the subgenual prefrontal cortex(SGPFC) and amygdala. Specifically we and others have demonstrated reduced volume in the left SGPFC and the right amygdala. Their pilot studies provide evidence that the contributions of genetic and environmental influences differ between the two regions. In recent studies of monozygotic twins discordant for MDD, the investigators have demonstrated that 1) left SGPFC volume reduction in MDD is consistently present in the twin with MDD in comparison to their unaffected co-twin and 2) right amygdala volume reduction and loss of usual amygdala asymmetry is demonstrated in both twins. Thus, they currently have evidence for at least two types of findings: structural changes which are present in ill twins (reduced left SGPFC) and changes which are present in at risk twins (amygdala). They hypothesize that these structural differences may be neurodevelopmental in origin and secondary to environmental or genetic factors, respectively. An alternative hypothesis is that these changes may be secondary to the illness process and represent a neurodegenerative or "scar " phenomenon. Relevant to the neurodevelopmental hypothesis, they have recently demonstrated significant age related increases in SGPFC volume in normal 8 to 21 year old girls in a cross-sectional design. The investigators propose a study examining an sample of epidemiologically ascertained young twins using high resolution MRI in order to examine four interrelated goals: 1) to quantify differences in prefrontal-limbic circuit neuromorphometry in young females with MDD; 2) to characterize neurodevelopmental or neurodegenerative patterns of change in these circuits using a prospective longitudinal design; 3) to estimate through twin genetic modeling the contribution of additive genetic or environmental influences to observed structural differences; and 4) to increase the power of neuromorphometric characterization through the use of automated cortex extraction methods and high-dimensional fluid warping in order to precisely delineate shape changes between subject populations and across developmental time periods. The twin subjects derive from a large established epidemiologically ascertained sample of female twins born in Missouri. The investigation of a twin population will allow for the direct estimation of genetic and environmental contributions to structural changes and developmental changes noted longitudinally. The combination of cutting edge genetic modeling and automated image analysis with newer sophisticated shape analysis offers a unique constellation of resources which will allow for a powerful exploration of the above hypotheses.