Insular Autonomic Function in Depression

抑郁症中的岛自主神经功能

• 批准号: 7898866
• 负责人: DONALD R ROYALL
• 金额: $ 37.25万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-18 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7898866
• 关键词: Address; Affect; Age; Alzheimer' s Disease; Antipsychotic Agents; Arrhythmia; Blood Pressure; Blood flow; Bradyarrhythmias; Brain Diseases; Cardiovascular Physiology; Cessation of life; Cholinesterase Inhibitors; Cocaine; Cognition; Communities; Data; Disease; Doctor of Philosophy; Drops; Elderly; Endogenous depression; Epilepsy; Fracture; Frequencies; Functional disorder; Heart Rate; Hip Fractures; Impaired cognition; Impairment; Insula of Reil; Left; Lesion; Lewy Bodies; Literature; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Mediating; Mediation; Mediator of activation protein; Medical; Mental Depression; Metabolism; Middle Cerebral Artery Infarction; Minority; Modeling; Morbidity - disease rate; National Institute of Drug Abuse; Nervous system structure; Neuraxis; Neurofibrillary Tangles; Outcome; Pathology; Patients; Personal Communication; Persons; Pharmaceutical Preparations; Population; Populations at Risk; Public Health; Reporting; Rest; Right-On; Risk; Screening procedure; Septuagenarian; Staging; Stroke; Sudden Death; Syncope; Testing; Variant; Visuospatial; base; depressive symptoms; falls; geriatric depression; heart rate variability; improved; in vivo; interest; mild neurocognitive impairment; mortality; pre-clinical; primary outcome; skills; spelling; white matter; young adult

DESCRIPTION (provided by applicant): Depressive symptoms in the elderly are associated with syncope, falls, and mortality. These associations are independent of comorbid conditions, and may reflect central nervous system effects. We have been investigating insular pathology as a cause of similar problems in Alzheimer's disease (AD). AD pathology reaches the insula at a preclinical stage, which may affect 40% of septuagenarians. Insular AD lesions, particularly on the right, are associated with bradyarrhythmias, Qtc intervals, and mortality. Moreover, right hemisphere metabolism and visuospatial skills predict mortality in stroke, and epilepsy as well as AD. However, we can now show that visuospatial cognitive impairments also mediate the effect of depressive symptoms on mortality. This implicates right hemisphere dysfunction in depression's mortality risk. Thus, the diproportionate risk of depression related mortality in the elderly may be mediated by their increased risk of subclinical structural insular lesions, including stroke, Lewy Body and /or subclinical AD pathology. This study will determine whether assymetric reductions in right insular blood flow by 3T magnetic resonance imaging (MRI) mediates the associaiton between depressive symptoms and measures of autonomic function, which have previously been associated with mortality in elderly populations. Our Primary Outcome will be the ratio of low frequency: high frequency components in the spectral distribution of Holter derived R-R frequency variations. Additonal heart rate variability (HRV) measures and longitudinal changes in heart rate HRV will be used in Secondary Analyses. Exploratory analyses will address other MRI pathological markers as potential mediators. Significant mediation would have important public health implications. 38% of community dwelling elderly with "Mild Cognitive Impairment" and could be at risk on the basis of subclinical insular AD pathology. 48% of middle cerebral artery strokes affect the insula. Minorities are disporportionately at risk for combined AD pathology and depressive symptoms. Moreover, medications may interact with insular pathology to affect mortality risk. Psychotropics, for example, affect insular blood flow. This may explain recent reports of increased mortality in eldely patients receiving atypical neuroleptics or cholinesterase inhibitors. Even anti-depressants may aggravate this risk, as they do not reliably improve depression related changes in HRV, and are themselves independent predictors of syncope, falls and hip fracture. Simple screening tests, such as clock- drawing, may identify those at greatest risk. PUBLIC RELEVANCE: Depressive symptoms in the elderly are associated with fainting spells, falls, bone fractures, and death. This study will determine whether right insular dysfunction may be a cause of these problems. Simple drawing tests may identify those at risk. These may include as many as 38% of community dwelling elderly with "Mild Cognitive Impairment" (MCI), or 24% of persons with middle cerebral artery strokes. Minorities may be disporportionately at risk. Moreover, insular dysfunction could explain recent reports of increased mortality in eldely patients receiving several types of psychotropic medications.

描述(由申请人提供)：老年人的抑郁症状与晕厥、跌倒和死亡有关。这些关联不受共病情况的影响，可能反映了中枢神经系统的影响。我们一直在研究岛状病理作为阿尔茨海默病(AD)类似问题的原因。AD病理在临床前阶段到达脑岛，这可能会影响40%的七旬老人。岛状AD损害，尤其是右侧，与缓慢性心律失常、QTC间期和死亡率有关。此外，右脑新陈代谢和视觉空间技能预测中风、癫痫和AD的死亡率。然而，我们现在可以表明，视觉空间认知障碍也介导了抑郁症状对死亡率的影响。这意味着右脑功能障碍与抑郁症的死亡风险有关。因此，老年人抑郁相关死亡的不成比例风险可能是由他们亚临床结构岛状病变的风险增加所介导的，包括中风、路易体和/或亚临床AD病理。这项研究将确定3T磁共振成像(MRI)右侧岛叶血流的不对称性减少是否可以中介抑郁症状和自主神经功能指标之间的关联，而自主神经功能指标以前曾与老年人群的死亡率有关。我们的主要结果将是Holter推导的R-R频率变化的频谱分布中的低频与高频分量的比率。其他心率变异性(HRV)测量和心率HRV的纵向变化将用于二次分析。探索性分析将把其他MRI病理标记物作为潜在的介体。重大调解将对公共卫生产生重要影响。38%的社区居住的老年人患有“轻度认知障碍”，根据亚临床的岛状AD病理可能处于危险之中。48%的大脑中动脉卒中影响脑岛。少数民族面临着合并阿尔茨海默病病理和抑郁症状的危险。此外，药物可能与岛叶病理相互作用，影响死亡风险。例如，精神药物会影响岛叶的血液流动。这可能解释了最近关于接受非典型抗精神病药物或胆碱酯酶抑制剂的老年患者死亡率增加的报道。即使是抗抑郁药也可能加剧这种风险，因为它们不能可靠地改善与抑郁相关的HRV变化，本身就是晕厥、摔倒和髋部骨折的独立预测因素。简单的筛查测试，如画钟，可能会识别出风险最高的人。公众相关性：老年人的抑郁症状与晕厥、跌倒、骨折和死亡有关。这项研究将确定右岛叶功能障碍是否可能是这些问题的原因之一。简单的绘图测试可能会识别出那些处于风险中的人。这可能包括多达38%的社区居住的老年人患有“轻度认知障碍”(MCI)，或24%的人患有大脑中动脉中风。少数族裔可能面临严重的风险。此外，岛叶功能障碍可以解释最近关于接受几种类型精神药物治疗的老年患者死亡率增加的报道。