McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
J Neurosci. 2013 Jun 26;33(26):10840-8. doi: 10.1523/JNEUROSCI.5747-12.2013.
Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key endocrine event associated with prepubertal increases in the adrenal production of androgens, most significantly dehydroepiandrosterone (DHEA) and to a certain degree testosterone. Adrenarche also coincides with the emergence of the prosocial and neurobehavioral skills of middle childhood and may therefore represent a human-specific stage of development. Both DHEA and testosterone have been reported in animal and in vitro studies to enhance neuronal survival and programmed cell death depending on the timing, dose, and hormonal context involved, and to potentially compete for the same signaling pathways. Yet no extant brain-hormone studies have examined the interaction between DHEA- and testosterone-related cortical maturation in humans. Here, we used linear mixed models to examine changes in cortical thickness associated with salivary DHEA and testosterone levels in a longitudinal sample of developmentally healthy children and adolescents 4-22 years old. DHEA levels were associated with increases in cortical thickness of the left dorsolateral prefrontal cortex, right temporoparietal junction, right premotor and right entorhinal cortex between the ages of 4-13 years, a period marked by the androgenic changes of adrenarche. There was also an interaction between DHEA and testosterone on cortical thickness of the right cingulate cortex and occipital pole that was most significant in prepubertal subjects. DHEA and testosterone appear to interact and modulate the complex process of cortical maturation during middle childhood, consistent with evidence at the molecular level of fast/nongenomic and slow/genomic or conversion-based mechanisms underlying androgen-related brain development.
人类和大猿是唯一被证明表现出肾上腺功能初现的物种，这是与青春期前肾上腺雄激素（主要是脱氢表雄酮（DHEA）和一定程度的睾酮）产生增加相关的关键内分泌事件。肾上腺功能初现也与儿童中期出现亲社会和神经行为技能同时发生，因此可能代表了人类特有的发育阶段。动物和体外研究都报告称，DHEA 和睾酮可根据所涉及的时间、剂量和激素环境，增强神经元存活和程序性细胞死亡，并可能竞争相同的信号通路。然而，目前尚无大脑激素研究检查 DHEA 和与睾酮相关的皮质成熟在人类之间的相互作用。在这里，我们使用线性混合模型来检查唾液 DHEA 和睾酮水平与发育健康的儿童和青少年 4-22 岁的纵向样本中皮质厚度变化之间的关系。DHEA 水平与左侧背外侧前额叶皮质、右侧颞顶联合区、右侧运动前皮质和右侧内嗅皮质的皮质厚度增加相关，这些区域的厚度增加发生在 4-13 岁之间，这一时期标志着肾上腺功能初现的雄激素变化。DHEA 和睾酮之间也存在相互作用，影响右侧扣带皮层和枕极的皮质厚度，这种相互作用在青春期前受试者中最为显著。DHEA 和睾酮似乎相互作用并调节儿童中期皮质成熟的复杂过程，这与分子水平上快速/非基因组和缓慢/基因组或基于转化的机制下雄激素相关的大脑发育的证据一致。
