DEVELOPMENTAL NEUROMORPHOMETRY IN YOUNG DEPRESSED TWINS

年轻抑郁双胞胎的发育神经形态学

• 批准号: 6629287
• 负责人: Kelly N Botteron
• 金额: $ 68.08万
• 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 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6629287
• 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：早发性重度抑郁症（MDD）是高度遗传性的 并与前额叶-边缘-纹状体回路的结构变化有关 结构.在早发性MDD的年轻成年女性中，研究者 研究表明，膝下前额叶皮层（SGPFC）的结构差异 和杏仁核具体来说，我们和其他人已经证明， 左侧的SGPFC和右侧的杏仁核。他们的初步研究提供了证据 遗传和环境影响的贡献在不同的人之间是不同的， 这两个地区。在最近对MDD不一致的单卵双胞胎的研究中， 研究者已经证明：1）MDD患者的左侧SGPFC体积减少， 与未受影响的双胞胎相比， 共同双胞胎和2）右杏仁核体积减少和普通杏仁核丢失 双胞胎都表现出不对称性。因此，他们目前有证据表明， 至少有两种类型的发现：存在于疾病中的结构变化 双胞胎（左侧SGPFC减少）和存在于风险双胞胎中的变化 （杏仁核）。他们假设这些结构差异可能是 起源于神经发育，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 与疾病过程相关，并代表神经变性或“疤痕“现象。 与神经发育假说相关，他们最近证明了 正常8 - 21岁儿童的SGPFC体积显著增加 女孩在一个横截面设计。研究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 为了检查四个相互关联的目标：1）量化 年轻女性MDD患者的额前边缘回路神经形态测量; 2） 表征神经发育或神经退行性变化模式， 这些电路使用前瞻性纵向设计; 3）通过 双胞胎遗传模型的贡献加性遗传或环境 对观察到的结构差异的影响;以及4）增加 通过使用自动皮层进行神经形态学表征 提取方法和高维流体翘曲，以便精确地 描述受试者群体之间和发育过程中的形状变化 时间段.这两个主题来自一个大型的既定的 在密苏里州出生的双胞胎女性样本。的 对双胞胎群体的调查将允许直接估计 遗传和环境对结构变化和发育的影响 纵向观察变化。结合最前沿的遗传建模 自动化图像分析和更新的复杂形状分析提供了一个 独特的资源组合， 上述假设。