Dutch Growth Research Foundation, Rotterdam, The Netherlands.
Department of Pediatrics, Erasmus Medical Centre Rotterdam/Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.
Schizophr Bull. 2017 Sep 1;43(5):1090-1099. doi: 10.1093/schbul/sbx052.
Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder caused by loss of the paternal 15q11.2-q13 locus, due to deletion (DEL), maternal uniparental disomy (mUPD), or imprinting center defects. Individuals with mUPD have up to 60% risk of developing psychosis in early adulthood. Given the increasing evidence for white matter abnormalities in psychotic disorders, we investigated white matter microstructure in children and adolescents with PWS, with a particular emphasis on the DEL and mUPD subtypes. Magnetic resonance diffusion weighted images were acquired in 35 directions at 3T and analyzed using fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD) values obtained by tract-based spatial statistics (TBSS) in 28 children and adolescents with PWS and 61 controls. In addition, we employed a recently developed white matter pothole approach, which does not require local FA differences to be spatially co-localized across subjects. After accounting for age and gender, individuals with PWS had significantly lower global FA and higher MD, compared with controls. Individuals with mUPD had lower FA in multiple regions including the corpus callosum, cingulate, and superior longitudinal fasciculus and larger potholes, compared with DEL and controls. The observed differences in individuals with mUPD are similar to the white matter abnormalities in individuals with psychotic disorders. Conversely, the subtle white matter abnormalities in individuals with DEL are consistent with their substantially lower risk of psychosis. Future studies to investigate the specific neurobiological mechanism underlying the differential psychosis risk between the DEL and mUPD subtypes of PWS are highly warranted.
普拉德-威利综合征（PWS）是一种复杂的神经遗传疾病，由父源 15q11.2-q13 位点缺失（DEL）、母源单亲二倍体（mUPD）或印记中心缺陷引起。mUPD 个体在成年早期有高达 60%的患精神病风险。鉴于在精神病障碍中存在越来越多的白质异常证据，我们研究了 PWS 儿童和青少年的白质微观结构，特别强调 DEL 和 mUPD 亚型。在 3T 上以 35 个方向采集磁共振扩散加权图像，并通过基于束的空间统计学（TBSS）在 28 名 PWS 儿童和青少年和 61 名对照中分析各向异性分数（FA）、平均值、轴向和径向扩散系数（MD、AD、RD）值。此外，我们采用了最近开发的白质坑洼方法，该方法不需要局部 FA 差异在受试者之间空间上局部化。在考虑年龄和性别后，与对照组相比，PWS 个体的整体 FA 明显降低，MD 明显升高。与 DEL 和对照组相比，mUPD 个体在多个区域（包括胼胝体、扣带回和上纵束）的 FA 较低，坑洼较大。mUPD 个体的观察到的差异与精神病个体的白质异常相似。相反，DEL 个体的细微白质异常与其精神病风险明显较低一致。未来的研究调查 PWS 的 DEL 和 mUPD 亚型之间差异精神病风险的特定神经生物学机制是非常必要的。
