Changes in brain function during adolescence and risk for depression in girls

描述（由申请方提供）：抑郁症发生率增加和出现性别差异的发育时间表明，青春期是理解女性抑郁症发生的因果机制的关键时期。青少年神经发育可能在抑郁症的病因学中发挥关键作用，但对青少年神经回路发育与抑郁症之间的界面知之甚少。在回应PA-09-108妇女的心理健康和性别/性别差异研究，我们将确定是否在神经回路的发展变化所从事的情绪唤起刺激与青春期抑郁症的女孩。将抑郁症状的发展轨迹映射到相关的神经系统上，将进一步加深我们对大脑功能成熟变化的理解，这些变化有助于与年龄相关的脆弱性。调查人员：基南博士、盖尔博士和福布斯博士是PI;他们两年前开始在抑郁症的神经科学方面进行合作。凯文·格里姆博士，一位专门从事纵向建模的统计学家，和艾莉森·希普韦尔博士，一位女性心理健康专家，是共同研究者。顾问是陈刚、罗纳德达尔、康斯坦斯·哈曼和丹尼尔·派恩博士。创新：信息处理中的大脑行为扰动是临床神经科学研究的主要焦点。青春期神经回路的发展变化对于理解这一时期精神病理学的出现至关重要。然而，迄今为止，还没有研究旨在验证这一假设，即青少年时期情感和认知回路之间的功能联系的发展与抑郁症发作有关，或者描述神经发育的模式，实际上赋予抑郁症发作的风险。方法：这项建议建立在最近完成的NIMH资助的女孩抑郁症前兆研究的基础上，其中记录了9-14岁的抑郁症症状和负面生活事件。一半的样本是根据抑郁症高风险指标选择的。对于这个PA，我们建议研究15-19岁的样本，并使用神经成像对抑郁和环境压力源进行年度评估，对情绪记忆和奖励处理进行年度评估。杏仁核-腹侧-外侧前额叶皮层（vlPFC）电路和纹状体-内侧前额叶皮层（mPFC）电路在情绪面孔记忆和奖励处理过程中的功能连接的发展模式，将分别在四个时间点捕获，环境压力暴露也是如此。环境：该提案涉及芝加哥大学、匹兹堡大学和加利福尼亚大学戴维斯分校的多机构调查。对抑郁、压力暴露和大脑功能的评估将在匹兹堡大学精神病学系和西方精神病研究所和诊所的情绪障碍神经成像实验室进行，该实验室在大脑功能和儿童精神病理学研究方面得到国际认可。

DESCRIPTION (provided by applicant): The developmental timing of the increase in the rate and the emergence of sex differences in depression points to adolescence as a critical period for understanding the causal mechanisms underlying the development of depressive disorders in females. Adolescent neural development is likely to play a key role in the etiology of depression, but little is known about the interface between the development of neural circuitry and depression across adolescence. In response to PA-09-108 Women's Mental Health and Sex/Gender Differences Research, we will determine if developmental changes in the neural circuitry engaged by emotionally evocative stimuli are related to adolescent depression in girls. Mapping developmental trajectories of depression symptoms onto relevant neural systems will further our understanding of the maturational changes in brain function that contribute to age-related vulnerability. Investigators: Drs. Keenan, Guyer and Forbes are the PIs; they began collaborating on the neuroscience of depression two years ago. Dr. Kevin Grimm, a statistician specializing in longitudinal modeling, and Dr. Alison Hipwell an expert in female mental health, are Co- Investigators. Consultants are Drs. Gang Chen, Ronald Dahl, Constance Hammen, and Daniel Pine. Innovation: Brain-behavior perturbations in information processing are a major focus of clinical neuroscience research. Developmental shifts in neural circuits during adolescence are critical to understanding the emergence of psychopathology during this period. No study to date, however, has been designed to test the hypothesis that development of the functional connections between affective and cognitive circuits during the adolescent period is related to depression-onset, or to characterize the patterns of neural development that in fact confer risk for depression onset. Approach: This proposal builds on a recently completed NIMH-funded study of precursors to depression in girls, in which depression symptoms and negative life events were documented from ages 9-14. Half of the sample was selected on measures indicative of high risk for developing depressive disorders. For this PA, we propose to study this sample from ages 15-19 years and to conduct annual assessments of depression and environmental stressors and annual assessments of emotional memory and reward processing using neuroimaging. Developmental patterns in functional connectivity between amygdala-ventral-lateral prefrontal cortex (vlPFC) circuitry and striatum-medial prefrontal cortex (mPFC) circuitry during memory for emotional faces and reward processing, respectively, will be captured across four time points, as will environmental stress exposure. Environment: This proposal involves a multi-institutional investigation at the Universities of Chicago, Pittsburgh, and California-Davis. Assessments of depression, stress exposure, and brain function will be conducted in the University of Pittsburgh's Department of Psychiatry and the Neuroimaging of Emotional Disorders Lab at Western Psychiatric Institute and Clinic, which is internationally recognized for research on brain functioning and child psychopathology.