Vasopressin Receptor Polymorphism and Social Cognition

描述（由申请人提供）：本提案的长期目标是了解黑猩猩在社会交际行为和认知方面的个体差异的遗传和神经生物学基础，黑猩猩是自闭症表型建模方面的潜在有价值的物种。拟议研究的一个目的是通过两个结构化任务来评估相对较大的黑猩猩样本（N = 290）在物种间交流中发起和参与共同注意力的能力。此外，在种间相互作用过程中，将使用观察方法评估社会性和沟通的措施。除了行为测量外，还将从每只黑猩猩获得DNA样本，并对AVPR1A（抗利尿激素）和OXTR（催产素）基因的等位基因频率和多态性变异进行评估。行为测试结果的差异不仅与这些基因的多态性有关，还与被试性别和早期抚养史等非遗传因素有关。这些分析将为遗传和非遗传因素对社会交际能力个体差异的作用提供有价值的信息。在体内的磁共振图像也将收集黑猩猩样本的一个子集。通过MRI，使用基于体素的全脑形态测定法（VBM）比较具有AVPR1A和OXTR基因不同基因型的受试者的灰质和白质完整性。这一分析将为这些基因在灰质和白质完整性发育组织中的作用提供关键数据。此外，基于VBM分析，区分不同基因型的感兴趣的大脑区域将被量化，随后应用于单个MRI扫描。然后，个体MRI测量将与行为表型相关联，以检查区分不同AVPR1A和OXTR基因型的大脑区域是否随后解释了社会交际能力的变化。集体研究将有助于我们了解影响皮质组织和社会交际能力的遗传和非遗传因素。

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.