GENETICS OF MONOAMINE ENDOPHENOTYPES AND MENTAL HEALTH

单胺内表型遗传学与心理健康

• 批准号: 7957888
• 负责人: JEFFREY A. ROGERS
• 金额: $ 12.47万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-06 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957888
• 关键词: Affect; Animals; Anxiety Disorders; Behavior; Behavioral; Biological Factors; Cerebrospinal Fluid; Chromosome Mapping; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Disease; Dopamine; Environmental Risk Factor; Family; Funding; Gene Expression; Generations; Genes; Genetic; Genome; Genotype; Grant; Human; Hydroxyindoleacetic Acid; Individual; Institution; Mental Health; Mental disorders; Methods; Methoxyhydroxyphenylglycol; Microsatellite Repeats; Modeling; Molecular; Neurotransmitters; Norepinephrine; Papio; Papio hamadryas; Prefrontal Cortex; Primates; Psychopathology; Quantitative Trait Loci; Research; Research Personnel; Resolution; Resources; Risk; Scanning; Schizophrenia; Serotonin; Source; Temperament; United States National Institutes of Health; Variant; depression; endophenotype; genetic linkage analysis; genetic pedigree; genome wide association study; monoamine; non-genetic; nonhuman primate; novel; response; social stress; trait

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The available data strongly suggest that the causes of psychiatric illnesses are complex, and that the risk of suffering from depression, schizophrenia, anxiety disorder and other psychiatric diseases is influenced by genetic inheritance, nongenetic biological factors and external environmental factors such as social stress. In addition, it is clear that monoamine neurotransmitters (serotonin, dopamine and norepinephrine) are related to the onset and treatment of depression, anxiety disorders and other psychopathologies. Despite the evidence for genetic influences on psychiatric disorders, on levels of monoamine neurotransmitters, and on normal variation in temperament related to disease, the specific genes that affect these traits are not well known. Whole genome scanning using linkage analysis in multi-generation pedigrees is a powerful method for locating functional genes that influence complex traits such as these. Unfortunately, for several reasons, this approach cannot be used with human families to locate genes that influence cerebrospinal fluid (CSF) levels of monoamines, or to investigate normal variation in behavior. In this project, we are conducting a whole genome linkage scan in a nonhuman primate model (baboons, Papio hamadryas). We are searching for genes that influence CSF levels of monoamine metabolites (5-HIAA, HVA and MHPG) and also investigating individual variation in temperament by subjecting each baboon to a behavioral challenge involving response to novel objects. All study animals will have already been genotyped for a linkage map consisting of 350 human microsatellite loci, with 7 cM resolution. We will also use gene expression array methods to assess the molecular effects of identified QTL loci in prefrontal cortex. Preliminary results from about 300 baboons indicate that all three monoamine metabolites and several behavioral responses to challenge are strongly heritable.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 可用的数据强烈表明，精神病的原因很复杂，患有抑郁症，精神分裂症，焦虑症和其他精神疾病的风险受遗传遗传，非遗传生物学因素和外部环境因素（例如社会压力）的影响。此外，很明显，单胺神经递质（5-羟色胺，多巴胺和去甲肾上腺素）与抑郁症，焦虑症和其他精神病理学的发作和治疗有关。尽管有遗传影响对精神疾病的影响，单胺神经递质水平以及与疾病有关的正常变化的证据，但影响这些特征的特定基因尚不清楚。在多代家谱中使用链接分析的整个基因组扫描是定位影响诸如此类复杂性状的功能基因的强大方法。不幸的是，由于几个原因，这种方法不能与人类家庭使用来定位影响脑脊液（CSF）单胺水平的基因，或者研究行为的正常变化。在这个项目中，我们正在非人类灵长类动物模型（Baboons，Papio Hamadryas）进行整个基因组链接扫描。我们正在寻找影响CSF水平单胺代谢产物（5-HIAA，HVA和MHPG）的基因，并通过使每个狒狒受到涉及对新物体反应的行为挑战来研究气质的个体变化。所有研究动物都将已经针对由350个人类微卫星基因座组成，分辨率为7 cm的连锁图。我们还将使用基因表达阵列方法来评估前额叶皮层中识别的QTL基因座的分子效应。大约300次狒狒的初步结果表明，所有三种单胺代谢产物和挑战的几种行为反应都是强烈的。