Pediatric depression and subsequent cardiac risk factors: a longitudinal study

儿童抑郁症和随后的心脏危险因素：一项纵向研究

• 批准号: 9068671
• 负责人: MARIA KOVACS
• 金额: $ 64.03万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-18 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9068671
• 关键词: 17 year old; 18 year old; 9 year old; Address; Adolescence; Adolescent; Adult; Adverse effects; Affect; Age; Behavioral; Biological; Biological Markers; Blood Pressure; Blood Vessels; C-reactive protein; Calmodulin 1; Cardiac; Cardiotoxicity; Cardiovascular Diseases; Child; Childhood; Clinical; Coronary heart disease; Data; Databases; Depressed mood; Depressive disorder; Development; Disease; Disease Marker; Elderly; Enrollment; Event; Exposure to; Family; Goals; Health; Health behavior; Heart Diseases; Hungary; Hypertension; Individual; Inflammation; Inflammatory; Intercellular adhesion molecule 1; Interleukin-6; LDL Cholesterol Lipoproteins; Lead; Life; Link; Longevity; Longitudinal Studies; Major Depressive Disorder; Measures; Mediating; Mental Depression; Metabolic syndrome; Morbidity - disease rate; Outcome; Pattern; Physiologic pulse; Physiological; Positioning Attribute; Prevention; Process; Prospective Studies; Public Health; Recording of previous events; Reporting; Research; Risk; Risk Factors; Risk Marker; Role; Sampling; Severities; Siblings; Smoking; Stress; Testing; Time; attributable mortality; base; cardiovascular risk factor; child depression; cigarette smoking; cohort; depressive symptoms; design; disability; disorder control; early onset; follow-up; heart disease risk; indexing; middle age; mortality; peer; pre-clinical; proband; public health relevance; sedentary; young adult

DESCRIPTION (provided by applicant): In this revised application, we addressed the IRG's concerns: we clarified the number/type of assessments on the 3 subject groups; proposed a further Hypothesis that mirrors better the use of childhood archival data about probands and their sibs; added ICAM-1 to our biological markers; and responded to various other concerns. Our study focuses on depression and coronary heart disease (CHD), which are enormous public health problems across the world. Depression not only predicts new onset CHD, and morbidity, and mortality in those with existing CHD but also is associated with behavioral risk factors (e.g. smoking, being sedentary) for eventual CHD. Although the depression-CHD link is well established, the causal role of depression is still being debated, and its most "cardiotoxic" features are yet to be confirmed. Notably, although both depression and CHD often originate in the pre-adult years, few studies have examined their association with behavioral CHD risk factors in a developmental context. We propose to assess 3 established samples of young adults in Hungary: a) probands (n=325), whom we have followed since childhood, when they had their first episode of major depression around the mean age of 9 years, b) never-depressed siblings of probands (n=325), and c) normal peer controls (n=155). We recently reported that: a) proband families have elevated rates of parental CV disease, b) by adolescence (mean age=17 years), being a proband predicted increased rates of behavioral risk factors for CHD (e.g., smoking, being sedentary), and c) rates of behavioral risk factors were highest among probands, lowest among controls, and intermediate among never depressed siblings of probands. The goal of the proposed study is to assess, for the first time, traditional biological risk factors (e.g., LDL cholesterol, blood pressure), along with behavioral risk factors, and several markers of CHD risk: pulse wave velocity, interleukin-6 and C-reactive protein (inflammation), ICAM-1 (endothelial function), and the metabolic syndrome. Our hypotheses address the levels of CHD risk markers as a function of subject group, the role of behavioral risk factors in adolescence in the link between depression and preclinical physiological outcomes, the impact of developmental trajectories of stress and risk variables on physiological outcomes among probands-sibs, and the most "cardiotoxic" clinical features of depression. Our extensive archival data on subjects' psychiatric history, family stress events, parental history of cardiovascular disease, socio-demographic variables, and various behavioral risk factors for CHD will yield a unique characterization of the unfolding relationships among depression, behavioral risk factors, and early markers of CHD risk. The sibling design will help isolate the contribution of depression to early markers of CHD risk by controlling for the adverse health impact of several family-based variables. Given the public health burden posed by depression and CHD, their study in young adults is particularly warranted, because risk factors and/or preclinical signs of CHD risk may be easier to modify earlier, rather than later, in the lifespan.

描述（由申请人提供）：在修订后的申请中，我们解决了IRG关注的问题：我们澄清了3个主题组的评估次数/类型；提出了一个进一步的假设，该假设更好地反映了关于先证者及其兄弟姐妹的童年档案数据的使用；将ICAM-1添加到我们的生物标记物中；并回应了其他各种问题。我们的研究重点是抑郁症和冠心病（CHD），这是世界范围内巨大的公共卫生问题。抑郁不仅预示着冠心病的新发、发病率和死亡率，而且还与最终导致冠心病的行为危险因素（如吸烟、久坐）有关。虽然抑郁症与冠心病之间的联系已经确立，但抑郁症的因果关系仍在争论中，其最“心脏毒性”的特征尚未得到证实。值得注意的是，尽管抑郁症和冠心病通常都起源于成年前，但很少有研究在发育背景下检查它们与行为冠心病危险因素的关系。我们建议评估匈牙利3个已建立的年轻人样本：a)先证（n=325），我们从童年开始跟踪，他们在平均9岁左右出现第一次严重抑郁症发作，b)先证的兄弟姐妹（n=325）， c)正常同伴对照（n=155）。我们最近报道：a)先证者家庭父母心血管疾病的发生率升高，b)在青春期（平均年龄=17岁），作为先证者预示着冠心病行为危险因素的发生率增加（例如，吸烟，久坐），c)行为危险因素的发生率在先证者中最高，在对照组中最低，在未患抑郁症的先证者的兄弟姐妹中居中。本研究的目的是首次评估传统的生物学危险因素（如低密度脂蛋白胆固醇、血压）、行为危险因素以及几种冠心病危险标志物：脉波速度、白细胞介素-6和c反应蛋白（炎症）、ICAM-1（内皮功能）和代谢综合征。我们的假设涉及冠心病风险标志物水平作为受试者群体的功能，青少年行为风险因素在抑郁症与临床前生理结果之间的联系中的作用，压力和风险变量的发育轨迹对可能的兄弟姐妹生理结果的影响，以及抑郁症最“心脏毒性”的临床特征。我们对受试者的精神病史、家庭压力事件、父母心血管病史、社会人口统计学变量和各种冠心病行为危险因素的广泛档案数据，将对抑郁症、行为危险因素和冠心病早期危险因素之间的关系进行独特的描述。通过控制几个基于家庭的变量对健康的不利影响，兄弟姐妹设计将有助于隔离抑郁症对冠心病风险早期标记的贡献。考虑到抑郁症和冠心病造成的公共卫生负担，他们对年轻人的研究特别有必要，因为冠心病风险的危险因素和/或临床前症状可能更容易在生命的早期而不是后期改变。