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: 10929813
• 负责人: kathleen r merikangas
• 金额: $ 292.33万
• 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/10929813
• 关键词: Adult; Affective; Age; Algorithms; Anxiety; Anxiety Disorders; Assessment tool; Australia; Autonomic nervous system; Biological; Biological Factors; Bioperiodicity; Bipolar Disorder; Bipolar I; Breeding; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Child; Childhood; China; Circadian Rhythms; Clinical; Cognitive; Collaborations; Communities; DSM-V; Data; Data Analyses; Data Collection; Data Science; Development; Diagnosis; Diagnostic; Diet; Disease; Disease susceptibility; Early Intervention; Electronics; Enrollment; Etiology; Evaluation; Event; Evolution; Family; Family Study; Future; Genetic; Goals; Hallucinations; Headache; Health; Health Sciences; Heart Rate; Holter Electrocardiography; Homeostasis; Hong Kong; Hormones; Individual; Inpatients; Institutional Review Boards; Interview; Investigation; Laboratories; Lead; Life; Link; Longevity; Magnetic Resonance Imaging; Marijuana Dependence; Measures; Medical; Medical History; Mental Health; Mental disorders; Metabolic; Methods; Migraine; Mood Disorders; Moods; Motor Activity; National Institute of Mental Health; Netherlands; Neurologic Examination; Neuropsychology; Nomenclature; Operations Research; Outpatients; Pain; Participant; Pathology; Patient Recruitments; Patient Self-Report; Patients; Pattern; Personality; Persons; Phase; Phenotype; Physical Examination; Physiological; Prevention; Process; Protocols documentation; Psyche structure; Psychiatry; Psychology; Psychopathology; Psychophysiology; Public Health; Publications; Recontacts; Recording of previous events; Reflex action; Reporting; Research; Research Personnel; Research Project Grants; Resolution; Review Committee; Risk; Role; Saliva; Salivary; Sampling; Series; Severities; Site; Sleep; Sleep Disorders; Specificity; Stress; Structure; Subgroup; Substance Use Disorder; Suicide; Suicide attempt; Surveys; Switzerland; Symptoms; Syndrome; System; Testing; Time; United States National Institutes of Health; Update; Valsalva Maneuver; Visualization; Work; actigraphy; anxiety spectrum disorders; blink reflexes; clinical center; clinical phenotype; cognitive testing; cohort; community setting; comorbidity; computer program; computerized; dashboard; data acquisition; data management; diagnostic criteria; diaries; disorder subtype; endophenotype; family structure; follow-up; genetic epidemiology; high risk; immune function; implementation measures; instrument; longitudinal design; method development; novel; physical conditioning; proband; psychosocial; psychotic; psychotic symptoms; recruit; sleep pattern; smartphone based assessment; social; stability testing; symptom cluster; tool; transmission process; user-friendly

To date, over 600 probands and nearly 1200 of their relatives have completed the study, including 200 children between the ages of 7-17 years. Approximately 600 individuals have also been evaluated at the NIH Clinical Center. Probands represent not only a large range of psychiatric disorders including mood and anxiety spectrum, but also substantial medical comorbidity related to sleep, migraine, pain, and cardiovascular conditions, as well as controls with minimal to no pathology. Over the past year, we focused on remotely collecting saliva and pooling existing samples for extracting genetics data, recontacting relatives for updated information, and expanding on our findings in new research tools and studies, including a newly approved research protocol under 000754-M, NCT05669703. During the past year, we have devoted substantial effort to validating and modernizing research operations. To streamline data collection, management and analyses, and to facilitate research collaboration, we continued to update our primary mental health interview to meet the latest diagnostic criteria (DSM-V) for integration into a sophisticated data capture system entitled the Diagnostic Assessment for Spectrum of Health (DASH). This system will utilize the power of modularized data capture combined with automated reporting features. We also began a comprehensive review to update our demographic, medical history, headache, sleep and family history instruments to incorporate as modules into the DASH. As a result, the DASH represents a comprehensive assessment tool measuring multiple domains of mental and physical health. Further, the DASH will have a user-friendly dashboard where specific modules assessing mental and physical health can be easily selected and administered. In addition to the DASH platform, we continued to work with experts to further develop new data science methods and tools, including efficient platforms to visualize multilevel data in R, a platform that combines data acquisition with data management and analysis, and computer programs to exploit the item-level data from diagnostic interviews and related measures, including algorithms for subthreshold syndromes, clinical phenomena, and self-report measures. Our collaboration with developers and external researchers has led to more developments in a new long-term data acquisition platform for health research (MindLogger), which we plan to use for cognitive testing, electronic diary applications, and tracking of mobile assessments in our studies. We have continued to devote research effort to collect follow-up data from families to maximize our ability to study causes, correlates, and consequences of these interrelated conditions. This involved administering diagnostic interviews and self-report clinical and psychosocial measures, in order to test the stability of these measures over time and track their relationship with emerging mental and medical disorders in families. We developed and obtained approvals by the NIMH Science Review Committee and the Institutional Review Board for a new research protocol (NIMH Rhythms and Blues Study) that will more deeply interrogate findings from our family study. By recruiting participants from the community as well as the NIMH Family Study, this new protocol employs an intensive longitudinal design with combined ecological and inpatient and outpatient laboratory assessments in the NIH Clinical Center to extensively characterize the associations among motor activity, circadian rhythms, and mood states by expanding the assessments of individual, physiologic, cognitive, and environmental correlates. For this new protocol, we have begun to pilot our updated diagnostic instruments, self-report surveys, and ecological measures, and tested a new computerized screener. We continue to devote major effort toward methods development and dissemination and analyses of dynamic phenotypes derived from actigraphy and electronic diaries, which permit investigation of fluctuations in core domains of mood disorders in the context of daily life. This work has been conducted in conjunction with collaborators across multiple sites including Lausanne, Switzerland; Sydney, Australia; Amsterdam, Netherlands; and Hong Kong, China. We are also continuing our work to examine mood disorder subtypes from childhood to adulthood, in collaboration with researchers in our parallel family study in Lausanne, Switzerland. In our most recent publication, we examined the occurrence of psychotic features within mood episodes in patients with bipolar 1 disorder (BD-1), and the associations with mood-congruent (MC) and mood-incongruent (MI) features. In a sample of thoroughly characterized patients with bipolar disorder (BD), our research suggests that patients with psychotic symptoms, particularly those with MI features, have more clinical severity in terms of a higher likelihood of reporting hallucinations, suicidal attempts, and comorbid cannabis dependence. These findings provide additional evidence supporting the distinction between BD-1 with and without psychotic features as well as the distinction between MI and MC psychotic features, highlighting the need for more thorough psychopathological evaluations to assess the presence of these symptoms in patients (Elowe et al, 2022). Public Health Impact: Integration of the clinical, neuropsychological, and psychophysiological measures within families will render an in-depth analysis of the mechanisms crucial to mood and anxiety disorders and their underlying diatheses. This will not only lead to a better fundamental, etiologic understanding of these conditions, but also may inform the development of novel treatment options, possible strategies for early intervention, and potential prevention in those with elevated risk for these conditions. Future Plans: During the next year, we plan to continue our efforts to center on the causes, correlates, and consequences of mood spectrum disorders, guided by our growing body of findings related to energy, motor activity, and other biorhythms linked to homeostasis; mental-medical comorbidity and the mechanistic association thereof; and psychiatric endophenotypes and risk processes associated with BD ranging from anxiety disorders to substance use disorders to suicide. Our analyses and new data collection will further discern subgroups for more intensive follow-up, and examination of key clinical and biological questions especially within the context of the NIMH Rhythms and Blues Study.

迄今为止，已有 600 多名先证者及其近 1200 名亲属完成了这项研究，其中包括 200 名 7 至 17 岁的儿童。 NIH 临床中心还对大约 600 人进行了评估。先证者不仅代表大量的精神疾病，包括情绪和焦虑谱系，而且还代表与睡眠、偏头痛、疼痛和心血管疾病相关的大量医学合并症，以及具有最小病理学或无病理学的对照。在过去的一年里，我们专注于远程收集唾液并汇集现有样本以提取遗传数据，重新联系亲属以获取最新信息，并扩展我们在新研究工具和研究中的发现，包括根据 000754-M、NCT05669703 新批准的研究方案。 在过去的一年里，我们投入了大量精力来验证和现代化研究运作。为了简化数据收集、管理和分析，并促进研究合作，我们继续更新我们的主要心理健康访谈，以满足最新的诊断标准 (DSM-V)，以便集成到名为“频谱诊断评估”的复杂数据采集系统中。健康（DASH）。该系统将利用模块化数据捕获与自动报告功能相结合的强大功能。我们还开始进行全面审查，以更新我们的人口统计、病史、头痛、睡眠和家族史工具，以将其作为模块纳入 DASH。因此，DASH 代表了一种衡量心理和身体健康多个领域的综合评估工具。此外，DASH 将拥有一个用户友好的仪表板，可以轻松选择和管理评估心理和身体健康的特定模块。除了DASH平台之外，我们继续与专家合作，进一步开发新的数据科学方法和工具，包括在R中可视化多级数据的高效平台、将数据采集与数据管理和分析相结合的平台以及可利用的计算机程序来自诊断访谈和相关测量的项目级数据，包括阈下综合征、临床现象和自我报告测量的算法。我们与开发人员和外部研究人员的合作导致了用于健康研究的新的长期数据采集平台（MindLogger）的更多发展，我们计划将其用于认知测试、电子日记应用程序以及在我们的研究中跟踪移动评估。 我们继续致力于研究工作，从家庭收集后续数据，以最大限度地提高我们研究这些相互关联的情况的原因、关联性和后果的能力。这涉及进行诊断访谈和自我报告的临床和心理社会测量，以测试这些测量随着时间的推移的稳定性，并跟踪它们与家庭中新出现的精神和医学疾病的关系。我们制定了一项新的研究方案（NIMH 节奏和布鲁斯研究）并获得了 NIMH 科学审查委员会和机构审查委员会的批准，该方案将更深入地探讨我们家庭研究的结果。通过从社区和 NIMH 家庭研究中招募参与者，这项新方案采用了密集的纵向设计，结合了 NIH 临床中心的生态和住院和门诊实验室评估，以广泛描述运动活动、昼夜节律和情绪之间的关联。通过扩大对个人、生理、认知和环境相关因素的评估来陈述。对于这个新方案，我们已经开始试点更新的诊断仪器、自我报告调查和生态措施，并测试了新的计算机筛查仪。 我们继续致力于方法的开发和传播以及对源自体动记录仪和电子日记的动态表型的分析，这使得研究日常生活中情绪障碍核心领域的波动成为可能。这项工作是与多个地点的合作者共同进行的，包括瑞士洛桑；澳大利亚悉尼；荷兰阿姆斯特丹；以及中国香港。我们还与瑞士洛桑平行家庭研究的研究人员合作，继续研究从儿童到成年的情绪障碍亚型。在我们最近的出版物中，我们研究了 1 型双相情感障碍 (BD-1) 患者情绪发作期间精神病特征的发生情况，以及与情绪一致 (MC) 和情绪不一致 (MI) 特征的关联。在对双相情感障碍 (BD) 患者进行彻底表征的样本中，我们的研究表明，有精神病症状的患者，特别是具有 MI 特征的患者，在报告幻觉、自杀企图和共病大麻依赖的可能性较高方面具有更高的临床严重性。这些发现提供了额外的证据支持 BD-1 有和没有精神病特征之间的区别以及 MI 和 MC 精神病特征之间的区别，强调需要更彻底的精神病理学评估来评估患者是否存在这些症状（Elowe 等人） ，2022）。 公共卫生影响： 家庭内临床、神经心理学和心理生理学测量的整合将深入分析情绪和焦虑障碍及其潜在素质的关键机制。这不仅可以使人们更好地了解这些疾病的基本病因，而且还可以为开发新的治疗方案、早期干预的可能策略以及对这些疾病高风险人群的潜在预防提供信息。 未来计划： 在接下来的一年里，我们计划继续努力，以我们不断增加的与能量、运动活动和其他与体内平衡相关的生物节律相关的发现为指导，集中研究情绪谱系障碍的原因、相关性和后果；精神医学共病及其机制关联；与 BD 相关的精神内表型和风险过程，包括焦虑症、药物滥用障碍和自杀。我们的分析和新数据收集将进一步辨别亚组，以便进行更深入的随访，并检查关键的临床和生物学问题，特别是在 NIMH 节奏和布鲁斯研究的背景下。

项目成果

Factorial structure and familial aggregation of the Hypomania Checklist-32 (HCL-32): Results of the NIMH Family Study of Affective Spectrum Disorders.

• DOI: 10.1016/j.comppsych.2018.03.010
• 发表时间: 2018-07
• 期刊: Comprehensive psychiatry
• 影响因子: 7.3
• 作者: Glaus J;Van Meter A;Cui L;Marangoni C;Merikangas KR
• 通讯作者: Merikangas KR

Familial aggregation of anxiety disorder subtypes and anxious temperament in the NIMH Family Study of Affective Spectrum Disorders.

NIMH 情感谱系障碍家庭研究中焦虑症亚型和焦虑气质的家族聚集。

• DOI: 10.1016/j.jad.2020.11.070
• 发表时间: 2021
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Iorfino,Frank;Marangoni,Ciro;Cui,Lihong;Hermens,DanielF;Hickie,IanB;Merikangas,KathleenRies
• 通讯作者: Merikangas,KathleenRies

Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis.

• DOI: 10.1001/jama.2009.878
• 发表时间: 2009-06-17
• 期刊: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
• 影响因子: 120.7
• 作者: Risch, Neil;Herrell, Richard;Lehner, Thomas;Liang, Kung-Yee;Eaves, Lindon;Hoh, Josephine;Griem, Andrea;Kovacs, Maria;Ott, Jurg;Merikangas, Kathleen Ries
• 通讯作者: Merikangas, Kathleen Ries

Epidemiology of mental disorders in children and adolescents.

• DOI: 10.31887/dcns.2009.11.1/krmerikangas
• 发表时间: 2009
• 期刊: Dialogues in clinical neuroscience
• 影响因子: 8.3
• 作者: Merikangas KR;Nakamura EF;Kessler RC
• 通讯作者: Kessler RC

Psychopathological precursors of the onset of mood disorders in offspring of parents with and without mood disorders: results of a 13-year prospective cohort high-risk study.

有或没有情绪障碍的父母的后代出现情绪障碍的精神病理学前兆：一项为期 13 年的前瞻性队列高风险研究的结果。

• DOI: 10.1111/jcpp.13307
• 发表时间: 2021
• 期刊: Journal of child psychology and psychiatry, and allied disciplines
• 作者: Rudaz,Dominique;Vandeleur,CarolineL;Gholam,Mehdi;Castelao,Enrique;Strippoli,Marie-PierreF;Marquet,Pierre;Aubry,Jean-Michel;Merikangas,KathleenR;Preisig,Martin
• 通讯作者: Preisig,Martin