青少年焦虑的神经易感性以及遗传机制
文献类型：学位论文
| 作者 | 丁晴雯
|
| 答辩日期 | 2023-06 |
| 文献子类 | 博士 |
| 授予单位 | 中国科学院大学 |
| 授予地点 | 中国科学院心理研究所 |
| 其他责任者 | 李新影 |
| 关键词 | 青少年焦虑 父母教养方式 行为遗传 神经易感性 基因易感性 |
| 学位名称 | 理学博士 |
| 学位专业 | 应用心理学 |
| 其他题名 | The neural susceptibility of adolescent anxiety and its genetic mechanism |
| 中文摘要 | Anxiety disorders are among the most common mental disorders, with a lifetime prevalence approaching 30%. Anxiety symptoms begin in childhood and adolescence and develop rapidly during adolescence, which are important predictors of future anxiety disorders. The genetic susceptibility of adolescent anxiety has been extensively studied and supported the differential susceptibility model, yet the underlying neural susceptibility are poorly understood. In the framework of brain‘ environment interaction, this study combined the neural, genetic, behavioral and environmental factors to investigate the neurobiological susceptibility of adolescent anxiety and its genetic mechanism, so as to determine the neural susceptibility indicators of anxiety. From the perspective of brain functional and brain structural susceptibility, the study is divided into two studies separately, and each study includes three sub-studies. Study 1 focused on whether brain functional features could serve as neural susceptibility indicators of anxiety, whereas Study 2 focused on whether brain structural features could serve as neural susceptibility indicators of anxiety. In sub-study 1，we explored whether resting-state network and brain structures could serve as differential susceptibility markers to moderate the influence of parenting styles in early adolescence on anxiety in middle adolescence, respectively. In sub-study 2, the twin genetic model was used to calculate the extent to which the susceptibility neural markers found in sub-study 1 were genetically determined. In sub-study 3, the relationships between three well-established susceptibility gene markers (BDNF, 5-HTT, and COM不)and neural susceptibility markers were investigated. We collected the longitudinal twin data with parenting measurements and candidate susceptibility gene determination in early adolescence, and anxiety measurements and brain structural and functional images in middle adolescence. In Study 1，we found that central executive network hypo-connectivity could serve as the neural susceptibility marker to significantly amplify the longitudinal influence of maternal hostility on adolescent anxiety, with the moderated pattern consistent with the differential susceptibility model. Higher anti-correlations between the anterior salience network and the default mode network significantly amplified the influence of paternal hostility on adolescent anxiety, consistent with the differential susceptibility model as well. Additionally, the central executive network connectivity is moderately heritable and is related to the well-established gene marker, BDNF. As such, central executive network hypo-connectivity could serve as a neural indicator for anxiety susceptibility. The results in Study 2 indicated that the greater cortical thickness of the left superior frontal gyros could serve as a susceptibility marker to amplify the influence of maternal hostility on adolescent anxiety, supporting the differential susceptibility model. We found a high heritability for the thickness of the left superior frontal gyros, though no specific relationship with the susceptibility gene markers was found. As such, greater cortical thickness in the left superior frontal gyros could also serve as an neural indicator for anxiety susceptibility. Results revealed the neural basis of individual differences in adolescent anxiety susceptibility and its potential link with genes. The brain functional and structural features could serve as promising neural indicators of differential susceptibility to adolescent anxiety. Conclusions contributes to the understanding that the neural sensitivity of the developing brain, similar to susceptibility genes, are sensitive to both positive and negative environments. The genetic link of neural susceptibility further implies the possibility of brain functional and structural characteristics to be the endophenotype of anxiety sensitivity. The findings contribute to the understanding of the biological mechanism of anxiety disorders and can also help clinicians identify the high-risk adolescents, and design appropriate prevention and intervention programs. |
| 英文摘要 | 焦虑症是最常见的精神障碍之一，终生患病率接近30%。焦虑症状始于童年和青春期，尤其在青春期发展迅速，是临床焦虑症的重要预测因素之一。青少年焦虑的基因易感性已经被广泛研究，且符合差异易感性模型，然而背后的神经机制即神经易感性却鲜为人知。在脑x环境交互作用的框架下，本研究将结合遗传、行为、环境与脑多维度地对青少年焦虑的神经易感性以及遗传机制进行考察，以期确定焦虑潜在的神经易感标记。研究从脑功能和脑结构易感性两个角度分为了两个研究，每个研究包括三个子研究，共六个子研究。研究一主要回答了大脑的功能特点是否有希望作为焦虑的神经易感性标记这一重要问题，而研究二主要回答了大脑的结构特点是否有希望可以作为焦虑的神经易感性标记这一重要问题。子研究一分别探究了静息态脑功能网络和大脑区域结构特点是否可以以差异易感性的模式去调节青春早期父母教养方式对于青春中期焦虑的影响。子研究二利用双生子模型计算在子研究一中找到的神经易感标记在多大程度上是由遗传决定的。子研究三考察了三个被广为研究的基因易感标记(BDNF, 5-HTT以及COMT)与神经易感标记之间的关系。 本研究采用纵向双胞胎设计在青春早期收集了父母教养以及易感基因数据，在青春中期收集了青少年的焦虑症状以及大脑结构和功能成像数据。研究一的结果发现，中央执行网络的低连接性能够作为焦虑的神经易感性标记去显著放大母亲敌意对于青少年焦虑的影响，调节模式与差异易感性模型一致。前突显网络和默认模式网络之间较高的反相关也以差异易感性的调节模式显著放大了父亲敌意对于青少年焦虑的影响。此外，中央执行网络连接程度受到遗传的影响，且与BDNF这一重要的基因易感标记有关。因此，中央执行网络的低连接性有希望作为焦虑易感性的神经标记。研究二的结果发现，左侧额上回较大的皮层厚度也能够作为焦虑的神经差异易感性标记显著放大了母亲敌意对于青少年焦虑的影响。虽然没有发现特定的易感基因标记与额上回皮层厚度之间的联系，在双生子模型中研究发现了左侧额上回厚度的高度遗传度。因此，左侧额上回较大的皮层厚度也有希望作为焦虑易感性的神经标记。 本研究从神经发育的角度揭示了青春期焦虑的个体差异来源以及与基因的潜在联系。大脑的功能和结构特点能够作为青少年焦虑的神经易感标记。此外，神经易感标记的调节模式与易感基因的调节模式一致，均符合差异易感性模型。这说明了发育中大脑的神经易感性，类似于易感基因，既对积极环境更易感，也对消极环境更易感，促进了对于神经适应性的理解。易感神经标记的遗传关联进一步暗示了大脑功能网络和结构特点成为焦虑易感内表型的可能性。在青春期这一重要发展节点考察焦虑症状的神经易感性以及遗传机制具有重要的理论和实践意义。研究结果有助于理解焦虑症早期的生物发生机制，也可以帮助临床工作者利用早期的易感标记去筛选高风险青少年，并设计适当的预防和干预计划。 |
| 语种 | 中文 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/46154]  |
| 专题 | 心理研究所_健康与遗传心理学研究室 |
| 推荐引用方式 GB/T 7714 | 丁晴雯. 青少年焦虑的神经易感性以及遗传机制[D]. 中国科学院心理研究所. 中国科学院大学. 2023. |
入库方式： OAI收割
来源：心理研究所
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