Stress, Neurodevelopment and the Emergence of Addictive Behaviors in Adolescence

压力，神经发育和青少年成瘾行为的出现（项目6/14）： 青少年时期是成瘾行为出现的关键时期， 发病率和事故、自杀和暴力行为的直接风险（ 这一年龄组的人），而且也导致终身重大医疗发病率和早期死亡率的增加。 虽然童年的压力被认为是成瘾行为发展的主要危险因素， 在青春期，缺乏对压力导致精神分裂症出现的机制的研究。 青少年的成瘾行为我们的试验数据表明，儿童期的压力会改变腹侧肌的发育， 前额叶皮层（VPFC）控制杏仁核和腹侧纹状体对情绪刺激的反应， 过度追求享乐刺激、冲动和成瘾行为。该项目建立了一个 共同Pis博士之间的新合作。Blumberg和Mayes汇集了他们各自的专业知识， 青少年大脑发育的多模态磁共振成像（MRI）研究和建模 心理社会因素对儿童适应性情绪和社会行为发展的影响 和青少年。这将提供独特的机会，研究如何心理社会压力，在童年 改变皮质边缘系统的发育，从而促进青少年成瘾行为的出现。这 研究小组将包括卡尔马博士、马祖雷博士、尼科尔斯博士、诺伦-霍克塞马博士、瑞安博士、王博士和其他财团 合作者整合观点，包括青少年医学，神经生物学，神经影像学， 神经心理学，儿科学，精神病学，心理学和妇女健康。梅斯博士一直在研究一种独特的 队列前瞻性自出生以来，现在进入青春期，仔细特点是每年两次 评估生物心理社会因素。我们计划从这个队列中选取70名14-17岁的青少年进行研究 年龄（50%女孩）：35岁有童年虐待史，35岁无虐待史。博士 Blumberg的小组将进行功能性MRI和扩散张量成像来检查局部大脑 皮质边缘回路对情绪刺激的反应， 以及电路中结构性白色物质连接的完整性。 联盟核心（项目13，14）的压力，生物因素和成瘾行为的措施将提供 丰富的研究机会，包括压力和遗传变异之间的相互作用， 杏仁核-腹侧纹状体-VPFC神经系统的生物胺调节（如2、3、7、8） 成瘾行为的出现。与波滕扎和Neumeister博士（7，8）的合作将提供 有机会研究青少年和成人之间的相似性和差异，以及新的治疗方法 测试（5，9，10）将为未来创新的预防和早期干预战略提供基础。

Stress, Neurodevelppment and the Emergence of Addictive Behaviors in Adolescence (Project 6 of 14): Adolescence is a critical period for the emergence of addictive behaviors that not only place adolescents at immediate risk for morbidity and for accidents, suicide, and violent behavior (the leading causes of death in this age group), but also contribute to lifelong increases in major medical morbidity and early mortality. Though childhood stress is known to be a major risk factor for the development of addictive behaviors in adolescence, there is a paucity of study of the mechanisms by which stress leads to the emergence of addictive behaviors in teens. Our pilot data suggest that childhood stress alters development of ventral prefrontal cortex (VPFC) control over amygdala and ventral striatum responses to emotional stimuli, resulting in excessive drive towards hedonic stimuli, impulsivity and addictive behaviors. This project establishes a new collaboration between co-Pis Drs. Blumberg and Mayes to bring together their respective expertise in multimodality magnetic resonance imaging (MRI) study of adolescent brain development and modeling the influences of psychosocial factors on the development of adaptive emotional and social behaviors in children and adolescents. This will provide unique opportunities to study how psychosocial stressors in childhood alter cortico-limbic development to contribute to the emergence of addictive behaviors in adolescence. This study team will include Drs. Kalmar, Mazure, Nicholls, Nolen-Hoeksema, Ryan, Wang and other consortium collaborators to integrate perspectives including Adolescent Medicine, Neurobiology, Neuroimaging, Neuropsychology, Pediatrics, Psychiatry, Psychology and Women's Health. Dr. Mayes has followed a unique cohort prospectively since birth, now entering adolescence, carefully characterized with biannual assessments for biopsychosocial factors. We plan to study 70 adolescents from this cohort, ages 14-17 years (50% girls): 35 with a history of childhood maltreatment and 35 without a history of maltreatment. Dr. Blumberg's group will perform functional MRI and diffusion tensor imaging to examine regional brain response to emotional stimuli within cortico-limbic circuitry, the functional connectivity between components within this circuitry, as well as the integrity of the structural white matter connections in the circuitry. Consortium core (Projects 13,14) measures of stress, biological factors and addictive behaviors will provide rich opportunities for study, including interactions between stress and genetic variations associated with biogenic amine regulation of the amygdala-ventral striatum-VPFC neural system (as in 2,3,7,8) in influencing the emergence of addictive behaviors. Collaboration with Drs. Potenza and Neumeister (7,8) will provide opportunities to examine similarities and differences between adolescents and adults, and novel treatments tested (5,9,10) will provide the basis for future innovative prevention and early intervention strategies.