Yu Wenquan, Lu Yi, Chen Tao, Xia Yikai, Tang Jing, Hussein Nimo Mohamed, Meng Shuang, Liu Xiaozheng, Liu Peining, Yan Zhihan
Department of Radiology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Department of Radiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.
J Affect Disord. 2023 Jul 1;332:176-184. doi: 10.1016/j.jad.2023.03.051. Epub 2023 Mar 23.
Central precocious puberty (CPP) patients are at significantly higher risk of emotional, mental, and behavioral disorders than those normal pubertal population. However, to date, the definite mechanism of how puberty hormones affect patients with CPP remains unclear. This regional homogeneity (ReHo) study aimed to explore the impact of premature hypothalamus-pituitary-gonadal (HPG) axis activation on brain function alteration in girls with CPP, meanwhile, to explore the relationship between gonadotropin and gonadal hormones levels, abnormal brain activity and cognitive function.
In this prospective study, a total of 85 girls who were suspected of having CPP were enrolled from the Child Healthcare Department of the Second Affiliated Hospital of Wenzhou Medical University Hospital from June 2018 to May 2021, including 41 CPP girls and 44 non-CPP girls. All participants collected the 0, 30, 60 min blood luteinizing hormone (LH), follicle-stimulating hormone (FSH), 0, 30 min estradiol (E2) and baseline cortisol (COR) and prolactin (PRL) concentrations after gonadotrophin-releasing hormone (GnRH) stimulating test. Resting-state magnetic resonance imaging (rs-MRI) scans were performed for all participants at 2 weeks before the GnRH stimulating test, voxel-wise ReHo was calculated in the standard frequency band (0.01-0.10 Hz), and in slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz). Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV) was also collected. Independent-sample t-test or Mann-Whitney U test was used to compare the differences between two groups. The correlation analysis among abnormal brain regions, serum hormone levels and WISC-IV scores were performed by Spearman or partial correlation analysis.
Compared to the non-CPP group, the CPP group showed higher regional homogeneity (ReHo) values in the left inferior temporal gyrus (ITG.L), as well as lower ReHo values in left superior temporal gyrus (STG.L), left superior occipital gyrus (SOG.L) and the right middle gyrus (MTG.R) in slow4.in slow5 frequency band, CPP group demonstrated decreased ReHo values in bilateral orbital part of superior frontal gyrus and medial superior frontal gyrus.
Due to the cross-section design of this study, further research is needed to explore the relationships between age, premature activation HPG axis and brain function changes.
Our findings demonstrate that premature HPG axis activation and alterations in puberty hormones, may lead to changes in brain activity and cognitive function. This rs-fMRI study may enhance our understanding of the neuroendocrine mechanisms of mood, behavior, and cognitive function alterations in patients with CPP.
中枢性性早熟（CPP）患者出现情绪、心理和行为障碍的风险显著高于正常青春期人群。然而，迄今为止，青春期激素如何影响CPP患者的确切机制仍不清楚。本区域一致性（ReHo）研究旨在探讨下丘脑-垂体-性腺（HPG）轴过早激活对CPP女童脑功能改变的影响，同时探讨促性腺激素与性腺激素水平、异常脑活动和认知功能之间的关系。
在这项前瞻性研究中，2018年6月至2021年5月从温州医科大学附属第二医院儿童保健科招募了85名疑似患有CPP的女童，其中包括41名CPP女童和44名非CPP女童。所有参与者在促性腺激素释放激素（GnRH）刺激试验后采集0、30、60分钟的血黄体生成素（LH）、卵泡刺激素（FSH）、0、30分钟的雌二醇（E2）以及基线皮质醇（COR）和催乳素（PRL）浓度。在GnRH刺激试验前2周对所有参与者进行静息态磁共振成像（rs-MRI）扫描，在标准频段（0.01-0.10Hz）以及慢4（0.027-0.073Hz）和慢5（0.01-0.027Hz）频段计算体素水平的ReHo。还收集了韦氏儿童智力量表第四版（WISC-IV）。采用独立样本t检验或曼-惠特尼U检验比较两组之间的差异。通过Spearman或偏相关分析对异常脑区、血清激素水平和WISC-IV评分进行相关分析。
与非CPP组相比，CPP组在左侧颞下回（ITG.L）显示出更高的区域一致性（ReHo）值，而在慢4频段的左侧颞上回（STG.L）、左侧枕上回（SOG.L）和右侧颞中回（MTG.R）以及慢5频段中显示出较低的ReHo值，CPP组在双侧额上回眶部和额上回内侧的ReHo值降低。
由于本研究的横断面设计，需要进一步研究以探索年龄、HPG轴过早激活与脑功能变化之间的关系。
我们的研究结果表明，HPG轴过早激活和青春期激素改变可能导致脑活动和认知功能变化。这项rs-fMRI研究可能会增强我们对CPP患者情绪、行为和认知功能改变的神经内分泌机制的理解。
