| 其他摘要 | 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. |
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