Immune System & Genetic Modulation of Brain Development & Behavior in Adolescence

免疫系统

• 批准号: 8071227
• 负责人: Consuelo Walss-Bass
• 金额: $ 55.52万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-17 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8071227
• 关键词: Adolescence; Adolescent; Age; Anxiety; Behavior; Behavioral; Bipolar Disorder; Blood; Brain; Cell Line; Child; Clinical assessments; DNA; Development; Diagnosis; Disease; Evaluation; Event; Exposure to; Family history of; Genes; Genetic; Genetic Variation; Genotype; Goals; Grant; Hostility; Immune; Immune system; Impulsivity; Inflammation; Inflammatory Response; Lead; Life; Longitudinal Studies; Lymphocyte; Measures; Mental Depression; Mental disorders; Moods; Onset of illness; Parents; Personality Traits; Physiological; Plasma; Play; Protocols documentation; Psychiatric Diagnosis; Regulation; Risk Marker; Role; Schizophrenia; Series; Signal Transduction; Stress; Structure; Symptoms; System; Techniques; Time; cohort; critical developmental period; cytokine; density; experience; high risk; immortalized cell; inflammatory marker; neuroimaging

DESCRIPTION (provided by applicant): Immune system abnormalities have been repeatedly observed in several psychiatric disorders, including severe depression, bipolar disorder and schizophrenia. However, it is not clear whether these alterations are an underlying cause or occur as a result of these disorders. The present study will investigate the role that inflammatory markers, as modulated by genetic make-up, play on regulation of functional and structural brain systems and behavior across the adolescent developmental period, prior to onset of psychiatric disorders. We will perform a longitudinal study of 160 high-risk adolescents, between the ages of 12 and 15 years at baseline, who have a parent diagnosed with depression, but who do not yet themselves have a psychiatric diagnosis. These children, will be compared to a cohort of age matched children (n=160) who have no family history of psychiatric disorders. We will examine blood levels of inflammatory markers in the adolescents throughout five years, and will correlate these levels with genetic variations within genes involved in the immune system, by using high-density genotyping techniques, to assess the role that genetic make-up may play in immune signaling. In parallel, each subject will undergo a series of behavioral and physiologic evaluations to assess several potential risk markers for psychiatric disorders. These evaluations include: a) stressful life events; b) clinical assessment of psychiatric symptoms and disorders; c) dimensional measures of behavior/personality traits including mood, anxiety, impulsivity and hostility; and d) functional and structural neuroimaging. At the time of the grant submission, baseline neuroimaging, DNA, plasma, lymphocytes, and immortalized cell lines have been collected and established in the cohort of 320 adolescents. During the proposed project period, adolescents will be reassessed yearly with the neuroimaging protocol being repeated twice at two year intervals. By performing these longitudinal studies, we will be able to identify how changes in immune signaling, as modulated by genetic make-up and in combination with exposure to adverse environmental experiences during a critical developmental period, may lead to changes in brain development and behavior which may in turn lead to disease onset. These studies will lead to a better understanding of the developmental origins of psychiatric disorders in which inflammation may play an important role. The goal of the study is to investigate genes involved in regulation of the inflammatory response during the adolescent developmental period, in order to detect early signs of abnormal brain development and behavior. In turn, cytokine levels and genetic variation will also be examined with relation to behavior and stress levels as well as brain structure and function.

描述（由申请人提供）：在多种精神疾病中反复观察到免疫系统异常，包括严重抑郁症、双相情感障碍和精神分裂症。然而，尚不清楚这些改变是根本原因还是这些疾病的结果。本研究将调查受基因组成调节的炎症标记物在精神疾病发作之前的整个青少年发育期对功能和结构性大脑系统和行为的调节所发挥的作用。我们将对 160 名基线年龄在 12 岁至 15 岁之间的高危青少年进行一项纵向研究，这些青少年的父母被诊断患有抑郁症，但他们自己尚未被诊断为精神病。这些儿童将与一组年龄匹配、没有精神疾病家族史的儿童 (n=160) 进行比较。我们将在五年内检查青少年血液中炎症标志物的水平，并通过使用高密度基因分型技术，将这些水平与参与免疫系统的基因内的遗传变异相关联，以评估遗传组成在免疫信号传导中可能发挥的作用。与此同时，每个受试者将接受一系列行为和生理评估，以评估精神疾病的几种潜在风险标记。这些评估包括： a) 生活压力事件； b) 精神症状和疾病的临床评估； c) 行为/人格特征的维度测量，包括情绪、焦虑、冲动和敌意； d) 功能和结构神经影像学。在提交拨款时，已在 320 名青少年队列中收集并建立了基线神经影像、DNA、血浆、淋巴细胞和永生化细胞系。在拟议的项目期间，青少年将每年重新评估一次，神经影像学方案每两年重复两次。通过进行这些纵向研究，我们将能够确定免疫信号的变化（由基因组成调节并与关键发育时期暴露于不良环境经历相结合）如何导致大脑发育和行为的变化，进而导致疾病的发生。这些研究将有助于更好地了解精神疾病的发育起源，炎症可能在其中发挥重要作用。该研究的目的是调查青少年发育期间参与调节炎症反应的基因，以检测异常大脑发育和行为的早期迹象。反过来，细胞因子水平和遗传变异也将被检查与行为和压力水平以及大脑结构和功能的关系。