Endocrine and Neurobiologic Events Accompanying Puberty

青春期伴随的内分泌和神经生物学事件

• 批准号: 8940012
• 负责人: Peter Schmidt
• 金额: $ 68.89万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8940012
• 关键词: 12 year old; Accounting; Adolescence; Adolescent; Adrenal Glands; Adult; Age; Amygdaloid structure; Anterior; Anxiety; Appearance; Behavior; Behavior Disorders; Behavior assessment; Blood Plasma Volume; Body Composition; Body mass index; Brain; Brain imaging; Brain region; Breast; Cell Line; Cells; Child; Classification; Cognitive; Corticospinal Tracts; DEXA; Data; Data Set; Development; Developmental Process; Diffusion Magnetic Resonance Imaging; Disease; Early-life trauma; Emotional; Endocrine; Endocrine system; Enrollment; Epidemiologic Studies; Estradiol; Evaluation; Event; Exposure to; Face; Fat Body; Female; Functional Magnetic Resonance Imaging; Future; Genetic Variation; Gonadal Steroid Hormones; Growth; High Pressure Liquid Chromatography; Hormonal; Hormones; Human; Image; Imaging Techniques; In Vitro; Individual; Institutes; Left; Life; Light; Link; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medial; Mental Depression; Metabolic; Methods; Monitor; Morbidity - disease rate; Myelin; Neurons; Neurosciences; Neurosciences Research; Outcome Measure; Performance; Phase; Physiological; Post-Traumatic Stress Disorders; Prevalence; Prevention; Process; Protocols documentation; Puberty; Regulation; Relative (related person); Reporting; Research; Research Personnel; Rewards; Roentgen Rays; Role; Sampling; Seminal; Sex Characteristics; Staging; Steroids; Stress; Structure; Substance abuse problem; System; Techniques; Testing; Thalamic structure; Time; Variant; Visceral; Visit; Water; Work; Wrist; bone age; boys; cingulate cortex; developmental neurobiology; girls; high risk; indexing; interdisciplinary approach; neurodevelopment; neuroimaging; neuronal patterning; neuropsychiatry; prepuberty; relating to nervous system; reproductive; reproductive function; sex; sexual dimorphism; steroid hormone; tandem mass spectrometry; white matter

The protocol involved in this project is 11-M-0251. This report includes work arising from the following protocol: NCT01434368. Recruitment for this demanding longitudinal study is in its early stages due in part to the successful development of imaging techniques required to measure gonadal volume in these children with Magnetic Resonance Imaging (MRI), the need for a designated functional MRI to be in place for the performance of brain imaging in this longitudinal, repeated measures study, and the successful piloting of several brain-activation paradigms to measure specific neural systems (e.g., the reward system) across puberty in children. We currently have sixty children enrolled in this study and several children have returned for repeat visits. We have observed several important methodologic variables that potentially will inform future studies: First, age alone is not sufficient to determine prepubertal status since we have identified approximately 10% of girls who show advanced Tanner breast stage at age 8. Breast development was unilateral and reflected early estradiol secretion in these girls. Second, neither chronologic age nor Tanner stage are sufficient markers of sex steroid (i.e., estradiol) exposure in boys and girls, since we have identified abnormally advanced bone age relative to their chronologic age and controlled for sex (as measured by left wrist x-rays) in approximately 10% of children screened for enrollment in this study. Finally, we have identified abnormally increased or decreased BMI (defined by normal BMI percentiles between 15 and 85th percentiles) which is accompanied by alterations in sex steroid secretion in approximately 17% of otherwise normal healthy children screened for this study thus emphasizing the importance of controlling for BMI in studies of the relationship between sex steroid secretion and brain development. We are currently investigating the effects of these early changes in gonadal activity as reflected by advanced bone age on brain structure and function. Preliminary results of neuroimaging studies in this project suggest that pubertal stage contributes to several measures of adolescent brain development and accounts for differences between adolescent and adult brain development that were brain region-specific. Diffusion tensor imaging (DTI), and myelin water fraction (MWF) imaging (mcDESPOT method) were acquired on a 3T scanner in 30 typically developing children (8-12 year-olds, 14 females). The relationship of DTI/MWF data to hormone and pubertal measures was tested. In this sample of 8-12 year-olds, bone age and Tanner stage were highly correlated with maturation of the corticospinal tracts as measured by both DTI and MWF. In contrast, gonadal volume and plasma steroid hormone levels were associated with minimal changes in MWF medial to the thalamus. These findings suggest that bone age and Tanner stage may covary with white matter maturation during the early pubertal phase, while gonadal volume and steroid hormones may be associated with more restricted changes in this early phase of development. Additionally, preliminary results from the study of these children combined with ongoing studies in adults shed light on some developmental processes relevant for vulnerability to early life trauma and future psychiatric morbidity. There is evidence that the structural integrity of the uncinate fasciculus, one of the major white matter tracts connecting limbic and prefrontal regions, predicts amygdala activation to fearful faces abnormal in some anxiety conditions including PTSD. However, few studies have investigated the developmental trajectory of the amygdalas structural and functional connectivity. In both children and adults, we examined the relationship between structural connectivity of the uncinated fasciculus and functional activation of the amygdala during viewing of aversive emotional faces. In children, increased integrity of the uncinate fasciculus predicted increased amygdala activity and functional connectivity with the anterior cingulate cortex during viewing of aversive emotional faces, while this relationship was not present in adults. These results suggest that white matter integrity may impact the functioning of the fronto-amygdalar circuitry differently in children than in the fully developed adult brain.

该项目涉及的协议为11-m-0251。该报告包括以下协议产生的工作：NCT01434368。 这项苛刻的纵向研究的招募是在其早期阶段，部分是由于成功开发了这些具有磁共振成像（MRI）的儿童所需的成像技术，需要进行指定的功能MRI，以便在此纵向的系统中进行大脑的表现，以衡量多个脑部的核对范围，并衡量了几个脑部的NE NE型衡量（E.GR），并衡量了几个脑部的NE NE型（E.G）（E.GR），并衡量了几个脑部的artivativativativativativativativative，并衡量了几个脑部的NE NE型（E.G）（E.系统）遍布儿童的青春期。 目前，我们有60名儿童参加了这项研究，有几个孩子返回重复访问。我们已经观察到了一些重要的方法论变量，这些变量可能会为未来的研究提供信息：首先，仅年龄就不足以确定青春期前的状态，因为我们已经确定了大约10％的女孩在8岁时表现出高级坦纳乳房的乳房。其次，由于我们已经确定了相对于年龄的年龄相对于年龄，并且在这项研究中筛查了大约10％的儿童，因此年龄段和制革商阶段都不是男孩和女孩的性类固醇（即雌二醇）暴露的足够标记（即雌二醇）暴露。最后，我们已经确定BMI异常增加或减少（由正常BMI百分位数在15％到85％之间），伴随着大约17％的正常健康儿童的性类固醇分泌的改变，因此对本研究进行了筛查，因此强调了BMI在性爱类固醇分泌和大脑发展之间控制BMI的重要性。 目前，我们正在研究晚期骨骼年龄对大脑结构和功能的性腺活性早期变化的影响。 该项目中神经影像学研究的初步结果表明，青春期阶段有助于青少年大脑发育的几种衡量标准，并解释了青少年和成人脑发育之间的差异，而大脑区域特异性是大脑区域特异性的。在30个典型发育中的儿童（8-12岁，14名女性）中，在3T扫描仪上获取了在3T扫描仪上获取扩散张量成像（DTI）和髓磷脂水分（MWF）成像（MCDESPOT方法）。测试了DTI/MWF数据与激素和青春期措施的关系。在这个8-12岁的样本中，如DTI和MWF所测量的那样，骨骼年龄和坦纳阶段与皮质脊髓束的成熟高度相关。相反，性腺体积和血浆类固醇激素水平与MWF内侧变化最小。这些发现表明，在青春期初期，骨骼年龄和坦纳阶段可能与白质成熟，而性腺体积和类固醇激素可能与在发育早期的早期阶段更加有限的变化有关。 此外，这些儿童的研究的初步结果与成年人的持续研究相结合，阐明了与早期生命创伤和未来精神病发病率有关的一些发展过程。有证据表明，在包括PTSD在内的某些焦虑条件下，Uncinate fasciculus的结构完整性是连接边缘和前额叶区域的主要白质区之一，它可以预测杏仁核激活与可怕的面孔异常。 但是，很少有研究研究杏仁核结构和功能连通性的发展轨迹。 在儿童和成年人中，我们研究了在观察厌恶情绪的面孔期间，无束筋膜的结构连通性与杏仁核的功能激活之间的关系。 在儿童中，不及格筋膜的完整性增加预测杏仁核活性的增加，并且在观察厌恶情绪的面孔期间与前扣带回皮层的功能连通性，而这种关系在成年人中不存在。 这些结果表明，白质的完整性可能会影响儿童的额叶 - 杏仁核电路的功能与在成年大脑中的功能不同。