Trajectories of Brain Connectivity, Depressive Symptoms, and Parenting in Puberty

 描述(由申请人提供)：青春期是抑郁发作的高危时期；15%的青少年，包括不成比例的大量女性，经历了严重抑郁障碍(MDD)15-17的发作。重要的是，青春期的MDD与疾病的高复发率有关。虽然大多数青少年直到15岁以后才达到MDD的标准，但亚综合征抑郁症状在10-15岁之间急剧上升，这一时期恰逢青春期。由于性腺激素受体位于大脑网络中，已被证明在抑郁症成年人和19-26岁的老年青少年中是异常的，科学家们推测，青春期通过改变与MDD13、27、28相关的大脑网络的发育轨迹来加速MDD的发生。具体地说，青春期被假设为改变组织结构的功能连通性和效率，其中显著网络(SN；涉及解释情绪显著刺激)、默认模式网络(DMN；涉及自我参照过程，如沉思)、执行控制网络(ECN：涉及情绪调节)13、27、29。我们还不了解青春期大脑网络连接轨迹和组织效率的个体变异性与抑郁症状轨迹变异性之间的关系的本质。我们也不知道青春期开始的时间是否或如何与大脑发育相互作用，以影响抑郁症状轨迹，这是一个关键问题，因为青春期性腺激素的释放与神经网络的持续发展相互作用。青春期是在一个社会背景下发生的；特别是，人们发现，儿童在青春期的发展会引起父母教养方式的变化，包括父母的热情和限制30，31。此外，父母在青春期表现出更高的权威育儿水平(温暖和限制都很高)的年轻人在青春期表现出较少的抑郁症状32-40，并且在青春期38、41期间抑郁症状的增加较少。神经成像研究表明，这种关系是由父母在SN、DMN和ECN14，42区域内大脑激活的与育儿相关的变异性所介导的。由于父母教养方式是青少年环境中一个与治疗相关且可改变的方面，我们建议考察父母教养方式对青少年大脑网络轨迹和抑郁症状发展的个体差异的贡献。我们建议在五年内每年前瞻性地评估80名健康的青春期前10岁和11岁的女孩。我们将在一项正在进行的大型纵向研究中增加三项额外的静息状态功能神经成像和青春期评估，我们将获得所有时间点的育儿行为报告。为了研究有患抑郁症风险的样本，我们将样本限制在社会经济地位较低的43-46岁女孩。通过澄清大脑发育的哪些特定方面以及何时出现问题，这项研究将有助于集中治疗，并提供可用于敏感监测治疗效果的大脑靶点。

 DESCRIPTION (provided by applicant): Adolescence is a period of high risk for the onset of depression; 15% of adolescents, including a disproportionately high number of females, experience an episode of Major Depressive Disorder (MDD)15-17. Importantly, MDD during adolescence is associated with high rates of recurrence of the disorder18. Although most adolescents do not meet criteria for MDD until after the age of 15, subsyndromal depressive symptoms rise precipitously between ages 10-15, the period coinciding with puberty. Because gonadal hormone receptors are located in brain networks that have been shown to be aberrant in depressed adults and older adolescents19-26, scientists theorize that puberty precipitates the onset of MDD by altering developmental trajectories of brain networks that are relevant to MDD13,27,28. Specifically, puberty is hypothesized to alter the functional connectivity and efficiency of organizational structure in the salience network (SN; implicated in interpreting emotionally salient stimuli), the default mode network (DMN; implicated in self-referential processes, such as rumination), the executive control network (ECN: implicated in emotion regulation)13,27,29. We do not yet understand the nature of the relation between individual variability in trajectories of brain network connectivity and organizational efficiency during puberty and variability in trajectories of depressive symptoms. We also do not know whether or how the timing of pubertal onset interacts with brain development to influence depressive symptom trajectories, a critical issue given that the release of gonadal hormones during puberty interacts with the ongoing development of neural networks. Puberty occurs in a social context; in particular, children's progression through puberty has been found to elicit changes in parenting style, including parental warmth and limit-setting30,31. Furthermore, youth whose parents exhibit higher levels of authoritative parenting (high in both warmth and limit-setting) during puberty exhibit fewer depressive symptoms32-40 and smaller increases in depressive symptoms through puberty38,41. Neuroimaging studies suggest that this relation is mediated by parenting-related variability in brain activation in regions within the SN, DMN, and ECN14,42. Because parenting style is a treatment-relevant and modifiable aspect of adolescents' environments, we propose to examine the contribution of parenting style to individual differences in the trajectories of adolescents' brain networks and in the development of depressive symptoms. We propose to prospectively assess 80 healthy, pre-pubertal 10- and 11-year-old girls annually for five years. We will add three additional resting-state functional neuroimaging and pubertal assessments to a large, ongoing longitudinal study, and we will obtain reports of parenting behaviors at all time points. To study a sample at risk for developing depression, we will limit our sample to low-socioeconomic-status girls43-46. By clarifying which specific aspects of brain development go awry and when, this study will help to focus treatments and provide brain targets that can be used to sensitively monitor treatment efficacy.