Family Study of Affective and Anxiety Spectrum Disorders

情感和焦虑谱系障碍的家庭研究

• 批准号: 8556939
• 负责人: kathleen r merikangas
• 金额: $ 171.77万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8556939
• 关键词: Address; Adult; Affective; Age; Anxiety; Anxiety Disorders; Attention; Atypical depressive disorder; Auras; Autonomic nervous system; Biological; Biological Factors; Bipolar Disorder; Breeding; Cardiovascular Diseases; Cardiovascular system; Child; Circadian Rhythms; Classic Migraine; Clinical; Cognitive; Communities; Comorbidity; Cues; DSM-IV; Data; Data Analyses; Data Set; Development; Diagnosis; Diagnostic; Diet; Disease; Disease susceptibility; Early treatment; Electronics; Enrollment; Evaluation; Event; Evolution; Family; Family Study; Family history of; Future; Genetic; Genomics; Goals; Headache; Headache Syndrome; Heart Rate; Heritability; Holter Electrocardiography; Hormones; Immunologics; Interview; Laboratories; Lead; Life; Link; Longevity; Magnetic Resonance Imaging; Major Depressive Disorder; Manic; Measures; Medical History; Mental Depression; Mental disorders; Metabolic; Methods; Migraine; Mood Disorders; Moods; National Institute of Mental Health; Neurologic Examination; Nomenclature; Paper; Parents; Participant; Patient Self-Report; Pattern; Pennsylvania; Personality; Persons; Phase; Phenotype; Physical Examination; Preventive Intervention; Psychiatry; Psychology; Psychopathology; Psychophysiology; Public Health; Recording of previous events; Recruitment Activity; Reflex action; Relative (related person); Reporting; Research; Resolution; Risk; Risk Factors; Role; Running; Saliva; Sampling; Series; Sex Characteristics; Sleep; Sleep Disorders; Source; Specificity; Speed; Stress; Structure; Symptoms; System; Testing; Time; United States National Institutes of Health; Universities; Update; Validation; Valsalva Maneuver; Work; Youth; actigraphy; base; blink reflexes; cardiovascular disorder risk; clinical phenotype; cohort; community setting; computerized; design; diaries; disorder subtype; endophenotype; family structure; follow-up; genetic epidemiology; high risk; hypomania; neuropsychological; novel; offspring; proband; sex; social; trait; transmission process

The major aims of this project have been accomplished through establishment of a large community based family study of adult probands who participate in comprehensive clinical and biologic assessments followed by comparable evaluations of their adult and child relatives. Recruitment of probands and evaluation of relatives are now near completion and analyses of the findings are underway. To date, we have enrolled 344 participants into the study from the community, and 238 from clinical sources. Our total enrollment from all sources is 786 probands, of which almost 500 have completed the study, and 1,283 relatives, including 175 children. Over the past year, 11 probands and 49 relatives have been recruited. Probands represent a range of disorders including: 30% with bipolar, 63% with depression, 60% with anxiety, 50% with migraine, and 22% without any of these conditions. During the next 3 months we plan to complete recruitment of probands and evaluation of relatives and will commence data analysis. In order to identify the core features of mood and anxiety disorders and their overlap with cardiovascular diseases and migraine, we have established a set of clinical, psychophysiological and neuropsychological measures. The comprehensive set of measures in the study are divided into three components: (1) clinical information that includes a semi-structured diagnostic interview for mood and anxiety disorders, structured diagnostic interviews for major headache syndromes and for sleep disorders, family history of psychiatric disorders, sleep disorders and headache syndromes, and a series of self-reported measures of symptoms, sleep patterns and personality, medical history, family structure, history and function, and major life and family events; (2) in person evaluation at the NIH Clinical Center that includes physical and neurological examination; autonomic nervous system evaluation using tilt and valsalva maneuver; laboratory measures of metabolic, cardiovascular, and immunologic function; psychophysiologic evaluation including startle reflex and eyeblink reflex; structural magnetic resonance imaging; a computerized cognitive assessment battery; and olfactory function; and (3) two-week assessment of daily activities including an electronic diary that assesses daily rhythms including mood, anxiety, sleep, stress, activity, diet, and social activities; heart rate reactivity using a holter monitor; activity and sleep using an actiwatch; and saliva hormones collected four times per day. In the past year, we have been running preliminary analyses on several of these clinical components and working with external collaborators to design and implement analyses of all of the measures in the study. This study has yielded substantial methodological developments including the development and validation of a structured diagnostic interview for headache syndromes; systematic assessment of the validity of the NIMH Family Study Diagnostic Interview for Affective Spectrum Disorders that was developed for this study compared to the Structure Clinical Interview for DSM-IV (SCID); and the validity of the NIMH Sleep Diagnostic Interview also developed for this study compared with sleep disorder diagnoses made by sleep experts. We have completed the primary analyses of the familial aggregation of mood disorder subtypes, their patterns of comorbidity, and their co-aggregation in relatives, and have submitted the principal paper that reports these findings. Likewise, we have also completed analyses of the familial aggregation of migraine and comorbid conditions. The major findings confirm the familial aggregation of bipolar disorder and major depression that has been found in earlier family studies of mood disorders but in a community based sample that suspended diagnostic hierarchies of earlier diagnostic systems. The most important finding that emerged from this study is the independent familial transmission of mania and depression suggesting that these two mood states may represent distinct underlying diatheses. The lack of familial aggregation of hypomania suggests that the bipolar spectrum concept may not be a valid entity. We also found strong evidence for familial specificity of atypical depression in probands and interviewed relatives, thereby confirming the validity of this subtype of depression. We also have investigated the familial aggregation of migraine and its links with mood disorders. We found a 2.6-fold increased risk of migraine in the relatives of probands with migraine, primarily attributable to migraine with aura. Sex of the proband was not associated with differential risk of migraine in relatives, thereby indicating that the sex difference in migraine cannot be attributed to genetic factors. Additional analyses that are now being investigated include the familial aggregation of subtypes of sleep disorders, early manifestations of mood and anxiety disorders in offspring of parents with mood spectrum disorders, and heritability analyses of both disorders and underlying traits. During the past several months, we have begun to examine the non-clinical measures as well, with substantial progress in analysis of the eyeblink reflex, actigraphy, olfactory measures and attention using the Attention Network Test. We have also conducted extensive analyses of links between cardiovascular disease and risk factors, migraine and depression in other data sets to develop specific hypotheses for the analyses of the family study data. Some intriguing findings that have emerged include: greater reactivity of the eyeblink reflex among those with migraine with aura compared to those without aura and non-headache controls; greater variability in activity among those with major depression; and increased orienting to cues in those with migraine with aura, and decreased speed of attention among those with depression. Public Health Impact: Integration of the clinical, neuropsychological and psychophysiological measures within families will allow us an in-depth analysis of the biological mechanisms crucial for mood and anxiety disorders and their underlying diatheses. This will not only lead to a better understanding of these conditions, and assist in identifying common genetic mechanisms, but may also lead to the development of novel treatment options and possible strategies for prevention and early intervention in those with elevated risk for these conditions. Future Plans: During the next year, we plan to follow up the probands and relatives to update the diagnostic status, and repeat the measures of circadian rhythms of activity, sleep and cognitive and mood states to test their stability and seasonal changes. We will complete enrollment of children under age 18 and follow up the 150 youth who have already participated in the study. Finally, we will examine common measures to match the NIMH local community to the supplemental study that we are now conducting in the Neurodevelopmental Genomics Study at the University of Pennsylvania.

该项目的主要目的是通过建立大型社区基于社区的家庭研究的成人研究，这些家庭研究参与了全面的临床和生物学评估，然后对其成人和儿童亲戚进行了可比的评估。 目前，招募探险和亲戚的评估即将完成，对发现的分析正在进行中。 迄今为止，我们已将344名参与者招募到社区的研究中，并从临床来源中招募了238名参与者。我们所有来源的总入学人数是786个证据，其中近500个已经完成了这项研究，其中1,283位亲戚，包括175名儿童。在过去的一年中，已经招募了11个证券和49个亲戚。概率代表一系列疾病，包括：30％的双极性，63％的抑郁症，60％的焦虑症，50％的偏头痛和22％没有这些疾病。 在接下来的三个月中，我们计划完成对亲戚的招聘和评估，并将开始数据分析。 为了确定情绪和焦虑症的核心特征及其与心血管疾病和偏头痛的重叠，我们建立了一组临床，心理生理和神经心理学措施。研究中的全面措施组成的三个组成部分：（1）包括半结构化的情绪和焦虑症的诊断访谈，对主要头痛综合症的结构性诊断访谈以及睡眠障碍的结构性诊断，对精神障碍，睡眠障碍和头痛综合症的家族史，以及一系列的自我症状的症状，是症状的症状，是症状的病史，和功能，以及重大的生活和家庭活动； （2）在NIH临床中心进行人身评估，其中包括身体和神经系统检查；使用倾斜和Valsalva操纵的自主神经系统评估； 代谢，心血管和免疫功能的实验室测量；心理生理评估，包括惊吓反射和透明反射；结构磁共振成像； 计算机认知评估电池；和嗅觉功能； （3）对日常活动的两周评估，包括电子日记，该电子日记评估日常节奏，包括情绪，焦虑，睡眠，压力，活动，饮食和社交活动；使用Holter监视器的心率反应性；使用Actiwatch活动和睡眠；和唾液激素每天收集四次。在过去的一年中，我们一直在对其中几个临床组件进行初步分析，并与外部合作者合作设计和实施研究中所有措施的分析。 这项研究产生了实质性的方法论发展，包括对头痛综合征的结构化诊断访谈的发展和验证；与DSM-IV（SCID）的结构临床访谈相比，对本研究开发的情感疾病的NIMH家庭研究诊断诊断访谈的有效性的系统评估；与睡眠专家进行的睡眠障碍诊断相比，这项研究的NIMH睡眠诊断访谈的有效性也开发了。 我们已经完成了情绪障碍亚型的家族聚集，合并症的模式以及它们在亲戚中的共同聚集的主要分析，并提交了报告这些发现的主要论文。同样，我们还完成了对偏头痛和合并症家族聚集的分析。主要发现证实了在早期的情绪障碍家庭研究中发现的躁郁症和严重抑郁症的家族聚集，但在基于社区的样本中，该样本暂停了早期诊断系统的诊断层次结构。这项研究中最重要的发现是躁狂和抑郁症的独立家族传播表明，这两个情绪状态可能代表了不同的潜在核心。缺乏家庭躁狂症的家族聚集表明，双极光谱概念可能不是一个有效的实体。我们还发现了有力的证据证明了探险中非典型抑郁症的家族特异性并接受了亲戚的访谈，从而确认了这种抑郁症亚型的有效性。我们还调查了偏头痛的家族聚集及其与情绪障碍的联系。我们发现，在偏头痛的亲属中，偏头痛的风险增加了2.6倍，主要归因于偏头痛。概率的性别与亲戚中偏头痛的差异风险无关，从而表明偏头痛的性别差异不能归因于遗传因素。现在正在研究的其他分析包括睡眠障碍亚型的家族性聚集，情绪谱系障碍父母的后代的情绪和焦虑症的早期表现以及对障碍和基本特征的遗传性分析。 在过去的几个月中，我们还开始检查非临床措施，并在分析eyeblink反射，动作法，嗅觉措施和使用注意网络测试方面取得了重大进展。我们还对其他数据集中心血管疾病与危险因素，偏头痛和抑郁症之间的联系进行了广泛的分析，以开发特定的假设，以分析家庭研究数据。一些有趣的发现包括：与没有光环和非头痛对照的偏头痛的人相比，偏头痛的反应性更大；重度抑郁症患者的活动差异更大；并提高了与Aura偏头痛的人的提示，并降低了抑郁症患者的关注速度。 公共卫生影响： 家庭内部的临床，神经心理学和心理生理措施的整合将使我们对对情绪和焦虑症及其基本核心至关重要的生物学机制进行深入分析。这不仅会导致对这些疾病的更好理解，并有助于确定常见的遗传机制，而且还可能导致发展新型治疗方案的发展以及预防和早期干预这些疾病风险升高的策略。 未来计划： 在明年，我们计划跟进概率和亲戚以更新诊断状态，并重复活动，睡眠和认知和情绪状态的昼夜节律节奏的措施，以测试其稳定性和季节性变化。我们将完成18岁以下儿童的入学人数，并跟进已经参加了这项研究的150名青少年。最后，我们将研究与NIMH当地社区与现在在宾夕法尼亚大学神经发育基因组学研究中进行的补充研究相匹配的常见措施。