Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, 94304, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, 94304, USA.
J Psychiatr Res. 2021 Feb;134:81-88. doi: 10.1016/j.jpsychires.2020.12.015. Epub 2020 Dec 11.
Fragile X syndrome (FXS) is the leading known inherited cause for intellectual disability. Due to mutations in the FMR1 gene, affected individuals are at risk for serious cognitive and behavioral symptoms and developmental disability. Clinical presentation varies considerably, and investigation of genetic factors not directly related to FMR1 may help better understand variability. The present study examined the BclI polymorphism of the glucocorticoid receptor gene NR3C1 in 43 individuals with FXS (28 females, age 16 to 25). Females with FXS who presented with one or more G alleles demonstrated attenuated symptoms of anxiety/depression (p = 0.038) and externalizing behaviors (p = 0.042) relative to individuals with the C/C allele. In the combined sample (males and females) structural neuroimaging data differentiated individuals with a G allele from those with the C/C genotype (p < 0.001). Key components of anxiety/fear neurocircuitry (amygdala, insula) contributed more (relative to other regions) to the model differentiating groups. These results indicate that GR polymorphisms are associated with an altered pattern of behavioral and brain development in FXS. This information is important for understanding and treating mood disorders and altered brain development among individuals with FXS. With further research, these findings could be informative for understanding anxiety and mood disorders more broadly.
脆性 X 综合征（FXS）是已知的导致智力障碍的主要遗传性病因。由于 FMR1 基因的突变，受影响的个体存在严重认知和行为症状以及发育障碍的风险。临床表现差异很大，对与 FMR1 不直接相关的遗传因素的研究可能有助于更好地理解变异性。本研究在 43 名 FXS 患者（28 名女性，年龄 16 至 25 岁）中检查了糖皮质激素受体基因 NR3C1 的 BclI 多态性。与具有 C/C 等位基因的个体相比，具有 FXS 的女性携带一个或多个 G 等位基因表现出焦虑/抑郁症状减轻（p=0.038）和外化行为减轻（p=0.042）。在合并样本（男性和女性）中，结构神经影像学数据将具有 G 等位基因的个体与具有 C/C 基因型的个体区分开来（p<0.001）。焦虑/恐惧神经回路的关键组成部分（杏仁核、岛叶）相对于其他区域更多地有助于区分组别的模型。这些结果表明，GR 多态性与 FXS 中行为和大脑发育的改变模式有关。这些信息对于理解和治疗 FXS 患者的情绪障碍和大脑发育改变很重要。随着进一步的研究，这些发现可能有助于更广泛地理解焦虑和情绪障碍。
