Adolescence, sex and timing of neural vulnerability

描述（由申请人提供）：青春期是一个独特的过渡时期，长期以来以情绪动荡、更容易上瘾和精神疾病（如抑郁症和精神分裂症）的发作而闻名。此时发生的神经重组可能会导致对包括压力在内的环境的脆弱性增加。特别是人类的前额叶皮层，在青春期的大小减少，不同性别的轨迹的时间和斜率不同（Lenroot等人，2007）。这意味着，男性和女性之间尺寸减小的细胞基础也必须不同。在人类和其他物种的青春期，前额叶皮层中的神经元、树突、突触和受体会发生修剪（Huttenlocher，1979;刘易斯，1997; Andersen et al，2000; Markham et al，2007），在少数情况下，修剪存在性别差异。修剪的时间将在这里研究的目标1，并在此时间的性别差异的影响将测试与目标2的压力。人类青春期期间的压力是已知的精神病理学倾向，并且可以促成症状（Grant等人，2004; Arnsten，2011），这表明正常修剪的破坏。青少年对压力的行为反应存在性别差异（罗密欧; 2010; Wilkin等人，2012）。这可能导致青少年发病期间精神分裂症的发病率和严重程度（男性>女性，1.4：1）以及抑郁障碍的终生发生率（女性>男性，2：1）（Abel et al，2010;帕克& Brotchie，2010）。因此，在青春期，性和压力在塑造潜在的脆弱回路中相互作用。我们的长期目标是了解青春期的神经变化是如何出错的，从而在性二态模式中沉淀出精神病理学。本研究的中心假设是，在青春期，修剪的时间存在性别差异，这导致了对压力的不同承受能力。

DESCRIPTION (provided by applicant): Adolescence is a unique transitional time, long noted for emotional turmoil, increased vulnerability to addiction and the onset of psychiatric disorders such as depression and schizophrenia. The neural restructuring that occurs at this time may result in increased vulnerability to the environment including stress. The prefrontal cortex of humans, in particular, decreases in size during adolescence with different timing and slope of trajectories in each sex (Lenroot et al, 2007). This means that the cellular basis for the size decrease must also differ between males and females. Pruning of neurons, dendrites, synapses and receptors occurs in the prefrontal cortex during adolescence in humans and other species (Huttenlocher, 1979; Lewis, 1997; Andersen et al, 2000; Markham et al, 2007), and there are indications of sex differences in pruning in the rare instances where they have been examined. The timing of pruning will be investigated here in Aim 1, and the implications of sex differences in this timing will be tested with stress in Aim 2. Stress during human adolescence is a known predisposition for psychopathology and can precipitate symptoms (Grant et al, 2004; Arnsten, 2011) which indicates a disruption of normal pruning. There are sex differences in the behavioral reaction to stress in adolescents (Romeo; 2010; Wilkin et al, 2012). This may contribute to the incidence and severity of schizophrenia during adolescent onset (1.4:1 male>female) as well as in the lifetime occurrence of depressive disorders (2:1 female>male) (Abel et al, 2010; Parker & Brotchie, 2010). Thus sex and stress interact in the sculpting of potentially vulnerable circuits during adolescence. Our long-term goal is to understand how the neural changes during adolescence can go awry to precipitate psychopathologies in a sexually dimorphic pattern. The central hypothesis of the present proposal is that there are sex differences in the timing of pruning during adolescence that result in differential vulnerabilitiesto stress.