Initiation of the Hypothalamic-Pituitary-Gonadal Axis in Young Girls Undergoing Central Precocious Puberty Exerts Remodeling Effects on the Prefrontal Cortex.

Di Yang,Lu Liu,Yaxin Zhu,Lu Zhou,Leah H Rubin,Wenjing Zhang,Xin Gao,Peining Liu,Xiaozheng Liu,Zhihan Yan,Bo Tao,Yu Chen,John A Sweeney,Yuchuan Fu

doi:10.3389/fpsyt.2019.00332

Abstract

Central precocious puberty (CPP) has been shown to exert significant effects on psychosocial development. These early puberty-related hormones and psychosocial functional changes are considered to be associated with specific brain development. However, the biological mechanisms underlying the sculpting of human brain architecture and modulation of psychosocial transformation by puberty-related hormonal maturation remain elusive, especially during the early phase of CPP. The current investigation aims to specify the brain regions in which early hormone-related maturation effects occur during CPP and their relationships with psychological functions. 65 young girls (aged 4.3–8.0 years) underwent structural imaging on a 3T MR system, completed psychological tests and performed the gonadotropin-releasing hormone (GnRH) stimulation test to identify hormonal manifestations of hypothalamic–pituitary–gonadal axis (HPG axis) activation. Based on the GnRH test, 28 young girls were identified with CPP, whereas the other 37 girls were identified with non-central precocious puberty (NCPP). Cortical parameters were calculated and compared between the two groups after adjusting for age, weight, and height. Brain regions showing group differences were extracted and correlated with serum hormone levels and psychological parameters. The CPP girls showed thinner cortices primarily in the right rostral middle frontal cortex. This morphological difference was positively correlated with stimulated estradiol (E2) levels. Further, higher E2 levels were significantly associated with higher hyperactivity scores. Premature HPG axis activation in CPP girls at an early stage appears to exert remodeling effects on brain anatomy, primarily in the prefrontal cortex, which may affect psychological development following the emergence of robust changes in sex hormones.

Highlights

Precocious puberty (PP) is an important issue that affects approximately 1 in 5,000–10,000 children [1, 2]
Over the last two decades, some studies have focused on the brain changes of Central precocious puberty (CPP) individuals, but the findings have mainly focused on suprasellar arachnoid cysts and hypothalamic hamartomas [12]
No significant differences were found in age, weight, height, and body mass index (BMI) between the CPP and non-central precocious puberty (NCPP) girls

Summary

Introduction

Precocious puberty (PP) is an important issue that affects approximately 1 in 5,000–10,000 children [1, 2]. In addition to physical problems, PP has been reported to be related to higher rates of psychological problems in patients when compared to healthy children [3, 4]. A previous longitudinal study of 2,607 girls with early menarche showed that early puberty might increase the risk of behavioral problems in young adolescent girls. Maturing girls are at risk of persistently higher delinquency and stronger negative peer influences [5]. These cognitive, behavioral, and emotional functioning changes are thought to be associated with specific brain development [6,7,8]. Identifying brain regions that contribute to psychological functioning in PP girls may be critical for interventions to prevent later negative outcomes

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