DEVELOPMENTAL NEUROMORPHOMETRY IN YOUNG DEPRESSED TWINS

年轻抑郁双胞胎的发育神经形态学

• 批准号: 6849314
• 负责人: Kelly N Botteron
• 金额: $ 67.58万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-02 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849314
• 关键词: adolescence (12-20); amygdala; brain imaging /visualization /scanning; clinical research; developmental neurobiology; disease /disorder onset; disease /disorder proneness /risk; dizygotic twins; family genetics; female; gene environment interaction; genetic models; human genetic material tag; human subject; interview; limbic system; longitudinal human study; magnetic resonance imaging; major depression; mental health epidemiology; middle childhood (6-11); monozygotic twins; morphometry; prefrontal lobe /cortex; structural biology

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.

描述：早期发作主要抑郁症（MDD）是高度遗传的 并与前额叶 - 纹状体电路的结构变化有关 结构。在早期发作MDD的年轻成年女性中，调查人员有 显示了亚属前额叶皮层（SGPFC）的结构差异 和杏仁核。具体而言，我们和其他人已经证明了体积减少 左SGPFC和右杏仁核。他们的试点研究提供了证据 遗传和环境影响的贡献之间有所不同 这两个区域。在最近关于MDD的单卵双胞胎不一致的研究中 研究人员已经证明1）MDD中的左SGPFC量减少为 与不受影响的人相比，与MDD持续存在 联合双胞胎和2）右杏仁核量减少和通常杏仁核的损失 在两个双胞胎中都证明了不对称性。因此，他们目前有证据 至少两种发现：生病中存在的结构变化 双胞胎（减少左SGPFC）和处于风险双胞胎中的变化 （杏仁核）。他们假设这些结构上的差异可能是 神经发育的起源，继发于环境或遗传因素， 分别。另一种假设是这些变化可能是次要的 疾病过程并代表神经退行性或“疤痕”现象。 与神经发育假设相关，他们最近证明了 正常8至21岁的SGPFC体积显着相关的SGPFC量增加 横截面设计的女孩。调查人员提出了一项研究 使用高分辨率的流行病学确定的年轻双胞胎样本 MRI以检查四个相互关联的目标：1）量化 MDD的年轻女性中的前额叶膜电路神经形态计； 2）到 表征神经发育或神经退行性的变化模式 这些电路使用前瞻性纵向设计； 3）通过 双基因建模添加遗传或环境的贡献 影响观察到的结构差异； 4）增加 通过使用自动皮质的神经形态计量表征 提取方法和高维流体扭曲以精确 描述受试者和跨发育之间的形状变化 时间段。双胞胎受试者源自大型建立 流行病学确定了在密苏里州出生的雌性双胞胎的样本。这 对双胞胎人群的调查将允许直接估计 遗传和环境对结构变化和发展的贡献 变化纵向指出。尖端遗传建模的组合 具有较新的复杂形状分析的自动图像分析提供了 独特的资源星座，将允许进行强大的探索 上述假设。