Vasopressin Receptor Polymorphism and Social Cognition

描述(由申请人提供)：这项提案的长期目标是了解黑猩猩在社会交流行为和认知方面的个体差异的遗传和神经生物学基础，黑猩猩是一个潜在的有价值的物种，用于模拟自闭症表型的各个方面。拟议研究的一个目的是对相对较大的黑猩猩样本(N=290)进行行为学特征描述，以了解它们在物种间交流中发起和参与联合注意的能力，这是在两个结构化任务中进行的评估。此外，在物种间相互作用期间，将使用观察方法来评估社会性和交流的衡量标准。除了行为测量外，还将从每只黑猩猩身上获取DNA样本和等位基因频率，并评估AVPR1A(加压素)和OXTR(催产素)基因的多态变异。行为指标上的表现变化将与这些基因的多态变化相关，也与包括性别和早期养育历史在内的非遗传因素有关。这些分析将提供有价值的信息，说明遗传和非遗传因素对社会交往能力的个体差异所起的作用。体内磁共振图像也将在黑猩猩样本的子集中收集。通过核磁共振成像，研究人员将使用基于体素的全脑形态测量技术(VBM)，对携带不同AVPR1A和OXTR基因的受试者进行灰质和白质完整性的比较。这项分析将提供有关这些基因在灰质和白质完整性发育组织中的作用的关键数据。此外，基于VBM分析，区分不同基因类型的大脑感兴趣区域将被量化，并随后应用于单独的MRI扫描。然后，个体核磁共振测量将与行为表型相关联，以检查区分不同AVPR1A和OXTR型的大脑区域是否随后解释了社交能力的差异。集体研究将有助于我们理解影响大脑皮层组织和社会沟通能力的遗传和非遗传因素。 公共卫生相关性：共同注意是儿童正常社会交流发展的关键技能和基础，在某些神经发育障碍中似乎会受到干扰，如自闭症。这项拟议的研究旨在调查遗传和早期养育因素在联合注意力发展中的作用，并确定可能解释这种行为的个体差异的大脑区域。

DESCRIPTION (provided by applicant): The long-term objectives of this proposal are to understand the genetic and neurobiological basis of individual differences in socio-communicative behavior and cognition in the chimpanzee, a potential valuable species for modeling aspects of the autism phenotype. One aim of the proposed studies is to behavioral characterize a relatively large sample of chimpanzees (N = 290) on their ability to initiate and engage in joint attention during interspecies communication as assessed on two structured tasks. In addition, measures of sociality and communication will be evaluated during interspecies interaction using observational methods. In addition to the behavioral measures, DNA samples will be obtained from each chimpanzees and allele frequencies and assessment of polymorphic variation in the AVPR1A (vasopressin) and OXTR (oxytocin) genes. The variation in performance on the behavioral measures will be correlated with polymorphic variation in these genes as well as in relation to non-genetic factors including sex and early rearing history of the subjects. These analyses will provide valuable information on the role of genetic and non-genetic factors on individual differences in socio-communicative competencies. In vivo magnetic resonance images will also be collected in a subset of the chimpanzee sample. From the MRI, subjects with different genotypes for the AVPR1A and OXTR gene will be compared on grey and white matter integrity using whole brain, voxel-based morphometry (VBM). This analysis will provide critical data on the role of these genes on the development organization of grey and white matter integrity. In addition, based on the VBM analysis, brain regions of interest that distinguish different genotypes will be quantified and subsequently applied to individual MRI scans. The individual MRI measures will then be correlated with the behavioral phenotypes to examine whether the brain regions distinguishing different AVPR1A and OXTR genotypes subsequently explain variation in socio-communicative competencies. The collective studies will contribute to our understanding of genetic and non-genetic factors that influence cortical organization and socio-communicative competencies. PUBLIC HEALTH RELEVANCE: Joint attention is a critical skill and foundation for normal socio-communicative development in children and appears to be disrupted in certain neurodevelopmental disorders, such as autism. The proposed studies aim to investigate the role of genetic and early rearing factors on the development of joint attention and to identify brain areas that might account for individual differences in this behavior.