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: 9569195
• 负责人: kathleen r merikangas
• 金额: $ 186.75万
• 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/9569195
• 关键词: Adult; Affective; Age; Anxiety; Anxiety Disorders; Attention; Attention deficit hyperactivity disorder; Atypical depressive disorder; Autonomic nervous system; Biological; Biological Factors; Biological Markers; Bipolar Disorder; Bipolar I; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Child; Clinic; Clinical; Collaborations; Collection; Communities; Comorbidity; Consent; DNA; Data; Data Aggregation; Data Analyses; Data Set; Detection; Development; Diagnostic; Diet; Disease; Disease susceptibility; Early Intervention; Ecological momentary assessment; Emotional Stability; Enrollment; Etiology; Evaluation; Event; Evolution; Family; Family Planning; Family Study; Family member; Future; Genetic; Genotype; Goals; Headache; Heart Rate; Holter Electrocardiography; Hormones; Individual; Intervention; Interview; Joints; Laboratories; Lead; Life; Longevity; Magnetic Resonance Imaging; Major Depressive Disorder; Manic; Measures; Medical; Medical History; Mental disorders; Metabolic; Methods; Migraine; Modeling; Mood Disorders; Moods; Motor Activity; National Institute of Mental Health; Neurologic Examination; Neuropsychology; Nomenclature; Odors; Participant; Patient Self-Report; Pattern; Personality; Persons; Phase; Phenotype; Physical Examination; Physical activity; Preparation; Preventive Intervention; Protocols documentation; Psyche structure; Psychiatry; Psychology; Psychopathology; Psychophysiology; Public Health; Publications; Recording of previous events; Recruitment Activity; Reflex action; Regulation; Research; Resolution; Risk; Risk Factors; Role; Running; Salivary; Sampling; Series; Site; Sleep; Sleep Disorders; Sleeplessness; Social Anxiety Disorder; Specificity; Stress; Structure; Subgroup; Suicide; Suicide attempt; Symptoms; Syndrome; System; Techniques; Temperament; Testing; Time; United States National Institutes of Health; Validation; Valsalva Maneuver; Work; Youth; actigraphy; anxiety spectrum disorders; base; blink reflexes; cardiovascular risk factor; clinical biomarkers; clinical phenotype; cognitive testing; cohort; community setting; computerized; design; diaries; disease classification; disorder subtype; endophenotype; family structure; follow-up; genetic analysis; genetic epidemiology; habituation; high risk; immune function; mobile computing; novel; offspring; olfactory threshold; phenotypic biomarker; potential biomarker; power analysis; proband; psychotic symptoms; social; social anxiety; suicidal behavior; symptom cluster; trait; transmission process

The major aims of this project have been accomplished through the 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 near completion and analyses of the findings are underway. To date, about 550 probands and about 1000 of their relatives have completed the study, including over 150 children between the ages of 7-17. Approximately 500 individuals have also been evaluated at the NIH Clinical Center. Probands represent a large range of disorders including mood, anxiety, sleep, migraine, and cardiovascular in addition to controls. We are now completing interviews with relatives who had not previously participated in the study. During the past year, we have continued to recruit new probands and family members. We are also following up the original sample, repeating interviews, ecological momentary assessment (EMA), actigraphy, and clinic measures, to assess the stability of these measures over time and track their relationship with emerging mental and medical illness in probands and family members, especially offspring. We have completed collection and genotyping of DNA samples, and we plan to conduct statistical genetic analyses during the coming year. We have completed analyses of the clinical validity of our interview, Diagnostic Interview for Affective and Anxiety Spectrum (DIAS), as compared to the Structured Clinical Interview for DSM Disorders (SCID), (Nakamura et al, in preparation). Results showed overall good concordance between the SCID and DIAS, with the DIAS frequently eliciting more information especially in regards to anxiety disorders. We have conducted extensive analyses of the clinical and biomarker phenotypes of familial aggregation data during the past year. We have also investigated comorbidity and co-aggregation of mood disorder subtypes with attention deficit hyperactivity disorder (ADHD), insomnia, cardiovascular risk factors, chronotype, and temperament (Iorfino et al, under review). Findings indicated that temperamental traits tapping anxiety are highly familial, but these traits do not appear to constitute manifestations of the same underlying diathesis as anxiety and mood disorders. Likewise, we found that ADHD does not appear to share a common underlying diathesis with bipolar disorder (BPD), whereas insomnia may reflect a common risk factors underlying mania and atypical depression. We have also devoted substantial effort to harmonize the measures and data sets from the Lausanne Family Study with the NIMH Family Study and plan to conduct joint analyses of the data on youth. We have analyzed joint data on comorbidity and co-aggregation of suicide and mental disorders, and shown that social anxiety disorder (SAD) is associated with suicide attempts in families (Ballard et al, submitted). We have nearly completed analyses on additional biomarkers that were collected on both probands and relatives. We found that bipolar 1 (BPI) disorder was characterized by lower average and greater variability in motor activity, and that those with BPD have greater reactivity across homeostatic regulatory systems of activity, sleep, mood and energy (Shou et al, 2017; Scott et al, 2017). Analyses of olfactory thresholds and detection revealed that people with BPI and major depression have deficits in odor identification, particularly attributable to the subgroup with psychotic symptoms (Kamath et al, under revision). Using ecological momentary sampling, we further showed that people with BPD have greater reactivity to positive events, whereas variability in mood and anxiety appears to be a trait marker of people with a history of mood disorders in general (Lamers et al, under review). We have employed a novel statistical technique to study the stability of emotional and attention states using fragmentation models (Johns et al, under review). We have now developed new EMA scripts that will be used in several sites to increase the generalizability of the samples and the power of these analyses. We are also analyzing sleep patterns and disorders as well as physical activity and their associations with mood disorder subtypes. Although there are no differences between people with mood disorder subtypes on the startle domains, we found that social anxiety is strongly associated with habituation and baseline startle. These startle domains are also highly familial. Therefore, we plan to follow up these findings by extending the sample to include more people with SAD and to recruit more family members. In summary, we have now confirmed with our preliminary analyses that people with BPI disorder differ from those with other subtypes of mood disorders and/or controls in terms of variability of motor activity, rhythms of sleep and activity, greater cross-domain reactivity, and greater autonomic reactivity. People with SAD tend to have greater reactivity to startle than those with mood disorders or controls. The major shift in the emphasis of the study is to follow up the sample to evaluate the stability of the clinical phenomena and potential biomarkers and their association with developmental manifestations of mood disorders and their core components. Publications in preparation/submitted/under review: -Nakamura E, et al. Validation of the Diagnostic Interview for Affective and Anxiety Spectrum Disorders (DIAS). -Iorfino F, et al. Familial aggregation of anxiety disorder subtypes and temperamental traits in the NIMH Family Study of Affective Spectrum Disorders. -Ballard E, et al. Familial aggregation of suicidal behavior and c-aggregation with mood and anxiety disorder subtypes. -Kamath V, et al. Olfactory processing in bipolar disorder, major depression, and anxiety. -Lamers F, et al. Mood variability and reactivity in mood disorder subtypes. -Johns J, et al. Fragmentation as a novel measure of stability in normalized trajectories of mood and attention assessed by electronic diaries. Public Health Impact: Integration of the clinical, neuropsychological and psychophysiological measures within families will render 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: The initial findings of our study have major implications for etiology, treatment, course and nosology of mood and anxiety disorders. However, the work requires replication in larger samples, re-assessment to examine stability of the findings, and collaboration with other sites to cover the full range of the spectrum of mood disorders, and increase the power of the study. We are now working to increase the number of probands with BPD and SAD in the study and are conducting comprehensive examinations of relatives, with a particular focus on youth ages 12-30. We continue to follow up the families already enrolled in the project to examine the stability of findings, re-consent participants for sharing of genetic data, and repeat the mobile technologies measures to examine their fluctuation over time. Based on the findings from study analyses, we plan to design and pilot interventions that stabilize regulation of activity, sleep and other daily rhythms in this and other samples. We also plan to establish a collaborative network of affiliated studies of community, high risk and clinical samples of youth with common measures of mood and motor activity.

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，他们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。 招募概率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，大约有550个概率和约1000个亲戚已经完成了这项研究，其中包括150多名7-17岁之间的儿童。 在NIH临床中心还评估了大约500个人。 概率代表了许多疾病，包括情绪，焦虑，睡眠，偏头痛和心血管外。 我们现在正在与以前从未参加过研究的亲戚完成访谈。 在过去的一年中，我们继续招募新的证据和家人。 我们还在跟踪原始样本，重复访谈，生态瞬时评估（EMA），动作法和诊所措施，以评估随着时间的推移这些措施的稳定性，并跟踪他们与探险和家庭成员中新兴的精神和医学疾病的关系，特别是后代。 我们已经完成了DNA样品的收集和基因分型，并计划在来年进行统计遗传分析。与DSM疾病（SCID）的结构化临床访谈相比，我们已经完成了访谈，情感和焦虑谱诊断访谈的临床有效性的分析（Nakamura等人，在准备中）。结果表明，SCID和DIAS之间的总体一致性，DIAS经常引起更多信息，尤其是在焦虑症方面。 在过去一年中，我们对家族聚集数据的临床和生物标志物表型进行了广泛的分析。我们还研究了与注意力缺陷多动障碍（ADHD），失眠症，心血管危险因素，表型和气质的合并症和情绪障碍亚型的共聚集（Iorfino等人，正在综述）。调查结果表明，气质特征嘲笑焦虑是高度家族性的，但是这些特征似乎并不构成与焦​​虑和情绪障碍相同的基础素质的表现。同样，我们发现ADHD似乎与双相情感障碍（BPD）共同具有共同的潜在素食，而失眠可能反映出躁狂症和非典型抑郁症的常见危险因素。 我们还致力于将洛桑家族研究的措施和数据集与NIMH家族研究相协调，并计划对青年数据进行联合分析。我们已经分析了关于自杀和精神障碍合并症和共同聚集的联合数据，并表明社交焦虑症（SAD）与家庭中的自杀企图有关（Ballard等人，提交）。 我们几乎完成了对在证据和亲戚上收集的其他生物标志物的分析。我们发现双极1（BPI）障碍的特征是运动活动的平均水平较低和较大的变异性，并且BPD的活动跨性稳态调节系统的反应性更大，睡眠，情绪和能量（Shou等，2017； Al，2017年）。对嗅觉阈值和检测的分析表明，BPI和大抑郁症患者的气味鉴定不足，尤其是归因于具有精神病症状的亚组（Kamath等人，在修订中）。 使用生态时刻的抽样，我们进一步表明，BPD患者对积极事件具有更大的反应性，而情绪和焦虑的变化似乎是具有一般情绪障碍史的人们的特质标记（Lamers等人，正在综述）。 我们采用了一种新颖的统计技术来使用碎片化模型研究情绪和注意状态的稳定性（Johns等人，正在综述）。现在，我们已经开发了新的EMA脚本，这些脚本将在多个站点中使用，以提高样品的普遍性和这些分析的功能。我们还正在分析睡眠模式和疾病以及体育锻炼及其与情绪障碍亚型的关联。 尽管惊吓领域的情绪障碍亚型的人之间没有差异，但我们发现社交焦虑与习惯和基线惊吓密切相关。这些惊吓领域也是高度家族性的。因此，我们计划通过将样本扩展到包括更多悲伤的人并招募更多家庭成员来跟进这些发现。 总而言之，我们现在已经通过初步分析确认，患有BPI疾病的人与其他心情障碍和/或对照组的人不同，就运动活动的可变性而言，睡眠和活动的节奏，更大的跨域反应性以及更大更大的自主反应性。与患有情绪障碍或控制的人相比，悲伤的人对惊吓的反应往往更大。该研究重点的主要转变是跟进样本，以评估临床现象和潜在生物标志物的稳定性及其与情绪障碍及其核心成分的发育表现的关联。 准备/提交/正在审查的出版物： -Nakamura E等。 验证情感和焦虑症障碍（DIAS）的诊断访谈。 -iourfino F等。 在NIMH家庭研究中，焦虑症亚型和气质特征的家族性聚集。 -Ballard E等。自杀行为和焦虑症亚型的C型c-家族聚集。 -Kamath V等。双相情感障碍，严重抑郁和焦虑中的嗅觉加工。 -Lamers F等。情绪障碍亚型的情绪变异性和反应性。 -Johns J等。片段化是通过电子日记评估的情绪和注意力的标准化轨迹的新型稳定性度量。 公共卫生影响： 家庭内的临床，神经心理学和心理生理措施的整合将对对情绪和焦虑症及其潜在核心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，而且还可能导致新的治疗选择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： 我们研究的最初发现对情绪和焦虑症的病因，治疗，课程和病因具有重大影响。但是，这项工作需要在较大的样本中复制，重新评估以检查发现的稳定性，并与其他站点进行协作，以涵盖各种情绪障碍范围，并增加研究的力量。 现在，我们正在努力增加BPD和SAD的概率数量，并正在对亲戚进行全面的检查，并特别关注12-30岁的青年。我们继续跟进已经参加该项目的家庭，以检查发现的稳定性，重新介绍遗传数据的参与者，并重复移动技术措施，以检查其随着时间的流逝。根据研究分析的发现，我们计划设计和试点干预措施，以稳定该和其他样本中的活动，睡眠和其他每日节奏的调节。我们还计划建立一个协作网络，涵盖社区，高风险和临床样本的关联研究，并具有共同的情绪和运动活动量度。