Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Masonic Institute for the Developing Brain (MIDB), University of Minnesota, Minneapolis, MN, USA; Institute of Child Development, College of Education and Human Development, University of Minnesota, Minneapolis, MN, USA; Department of Pediatrics, University of Minnesota Medical School, University of Minnesota, Minneapolis, MN, USA.
Psychoneuroendocrinology. 2021 May;127:105154. doi: 10.1016/j.psyneuen.2021.105154. Epub 2021 Feb 11.
In females, pubertal onset appears to signal the opening of a window of increased vulnerability to the effects of stress on neurobehavioral development. What is the impact of pubertal timing on this process? We assessed the effects of pubertal timing and stress on behavior and amygdala functional connectivity (FC) in adolescent female macaques, whose social hierarchy provides an ethologically valid model of chronic psychosocial stress. Monkeys experienced puberty spontaneously (n = 34) or pubertal delay via Lupron treatment from age 16-33 months (n = 36). We examined the effects of stress (continuous dimension spanning dominant/low-stress to subordinate/high-stress) and experimental pubertal delay (Lupron-treated vs. Control) on socioemotional behavior and FC at 43-46 months, after all animals had begun puberty. Regardless of treatment, subordinate monkeys were more submissive and less affiliative, and exhibited weaker FC between amygdala and dorsolateral prefrontal cortex and stronger FC between amygdala and temporal pole. Regardless of social rank, Lupron-treated monkeys were also more submissive and less affiliative but were less anxious and exhibited less displacement behavior in a "Human Intruder" task than untreated monkeys; they exhibited stronger FC between amygdala and orbitofrontal cortex. No interactions between rank and Lupron treatment were observed. These similar behavioral outcomes may reflect the common factor of delayed puberty - whether this is stress-related (untreated subordinate animals) or pharmacologically-induced (treated animals). In the brain, however, delayed puberty and subordination stress had separable effects, suggesting that the overlapping socioemotional outcomes may be mediated by distinct neuroplastic mechanisms. To gain further insights, additional longitudinal studies are required.
在女性中，青春期的开始似乎标志着对压力对神经行为发育影响的易感性增加的窗口期的开启。青春期开始的时间对这一过程有什么影响？我们评估了青春期开始的时间和压力对青春期前雌性猕猴行为和杏仁核功能连接（FC）的影响，其社会等级提供了慢性心理社会压力的一种与进化相关的有效模型。猴子自然经历青春期（n=34）或从 16 至 33 个月龄时用 Lupron 治疗经历青春期延迟（n=36）。我们研究了压力（从支配/低压力到从属/高压力的连续维度）和实验性青春期延迟（Lupron 治疗与对照）对 43-46 个月龄时社会情感行为和 FC 的影响，此时所有动物都已经开始青春期。无论治疗如何，从属猴子的顺从性更高，亲社会性更低，并且杏仁核和背外侧前额叶皮层之间的 FC 较弱，而杏仁核和颞极之间的 FC 较强。无论社会等级如何，Lupron 治疗的猴子也更顺从，亲社会性更低，但在“人类入侵者”任务中比未治疗的猴子更不焦虑，表现出更少的移位行为；它们的杏仁核和眶额皮层之间的 FC 更强。未观察到等级和 Lupron 治疗之间的相互作用。这些类似的行为结果可能反映了青春期延迟的共同因素——无论是与压力相关的（未治疗的从属动物）还是药物诱导的（治疗动物）。然而，在大脑中，青春期延迟和从属压力具有可分离的影响，这表明重叠的社会情感结果可能由不同的神经可塑性机制介导。为了获得更多的见解，需要进行额外的纵向研究。
