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小儿双相情感障碍脑功能及病程研究

2026年9月22日 更新者:National Institute of Mental Health (NIMH)

儿童和青少年严重情绪和行为失调的特征和病理生理学

This study seeks to learn more about the symptoms of severe mood dysregulation in children and adolescents ages 7-17. Children and adolescents with severe mood dysregulation (SMD) display chronic anger, sadness, or irritability, as well as hyperarousal (such as insomnia, distractibility, hyperactivity) and extreme responses to frustration (such as frequent, severe temper tantrums). Researchers will describe the moods and behaviors of children with these symptoms and use specialized testing and brain imaging to learn about the brain changes associated with this disorder.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

Objective:

Irritability is a common and impairing clinical presentation in youth. Despite its significant public health impact, the clinical course and pathophysiology of irritability remains poorly understood. Chronic and severe irritability is the primary symptom of the new DSM-5 diagnosis, disruptive mood dysregulation disorder (DMDD), is an associated symptom of other pediatric disorders including Attention-Deficit/Hyperactivity Disorder (ADHD), and can be a clinical precursor to Major Depressive Disorder (MDD) and anxiety disorders. In addition, irritability is a trait distributed continuously in youth, thereby fitting well within the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) initiative.

Clinically impairing irritability in children and adolescents began to gain more attention as interest grew in the diagnosis of pediatric bipolar disorder. Beginning in the 1990s, child psychiatry researchers suggested that while pediatric bipolar disorder can present with distinct episodes of mania or hypomania as in adults, the more typical pediatric presentation was chronic, severe irritability and hyperarousal symptoms. However, data collected under this protocol comprise a series of longitudinal, family, behavioral, and pathophysiological studies that differentiated classically defined episodic pediatric bipolar disorder from chronic irritability without distinct manic or hypomanic episodes. These findings are consistent with reports from other groups and meta-analyses.

Among the several strands of research designed to differentiate pediatric bipolar disorder from chronic irritability, longitudinal studies provide the strongest evidence that these two phenotypes are distinct. Children with chronic irritability are at elevated risk for later depression, but not manic episodes. Thus, youth with MDD (with and without prior DMDD) are an important comparison group to explore, and we are examining the developmental trajectory, phenomenology, behavioral correlates, and underlying neural mechanisms of chronic irritability and MDD in youth. Further, because irritability and ADHD symptoms are highly comorbid in youth, participants with ADHD are an important comparison group in our work on irritability.

The current translational model of irritability emphasizes the role of abnormal threat and reward processing, but also underlines the relevance of environmental factors in the emergence and maintenance of irritability. More precisely, it is assumed that irritable children experience environments, where rewards and punishments are inconsistently delivered leading to unintentional reinforcement of disruptive behavior through the parents. Reasons for this inconsistent parent behavior could be manifold spanning instrumental learning deficits and exaggerated responses to threat and frustrative non-reward in the parents themselves as well as lack of knowledge regarding learning principles and increased levels of stress. These factors might contribute to instrumental-learning deficits in the children increasing frequency and intensity of temper outbursts. Heightened levels of chronic irritability, another symptom of DMDD, might be more associated with features of the parent-child interaction. There is a rich literature within the framework of attachment theory showing that behavior of children with anxious-resistant insecure attachment is characterized by a general angry tone and is also associated with increased amygdala responses to negative social scenes. In addition, it was also shown that highly irritable infants are less sociable in terms of being less responsive and more fearful towards others and displaying an angry emotional tone in general as toddlers when they had been insecurely attached and more sociable when they had been securely attached. Adding another layer of complexity, it is also conceivable that inconsistent parent behavior diminishes parent's perceived trustworthiness. This could be of relevance as recent studies showed that persons are less willing to delay rewards - an action bound to increase levels of frustration - if their interaction partner is perceived as little reliable.

The overall goal is to gain a clearer understanding of the environmental factors contributing to irritability in order to inform treatment and improve the outcome for children. As part of this overall goal, we plan to collect information on numerous environmental factors. First, we plan to investigate parents of youth with DMDD enrolled in this study and subthreshold DMDD enrolled in this study in order to determine clinical, behavioral, neuropsychological, neurophysiological and neuroanatomical features of the parents that contribute to the symptomatology in the children and adolescents. Further, we plan to examine parent-child interaction and its influence on irritability observed in the youth. Second, we plan to investigate the role of environmental stressors on youth's irritability symptoms.

Study population:

There are 6 separate populations being studied in this protocol:

  1. Children and adolescents between the ages of 7-17 years old who meet criteria for DMDD or subthreshold DMDD.
  2. Caregivers of children and adolescents, who meet criteria for DMDD or subthreshold DMDD and are enrolled in 02-M-0021, and are 25-85 years old will be studied.
  3. Healthy volunteer children and adolescents between the ages of 7-17 years old.
  4. Healthy volunteer adults between the ages of 18-25 years old.
  5. Children and adolescents between the ages of 11-17 years old who meet criteria for major depressive disorder (MDD).
  6. Children and adolescents between the ages of 8-17 years who meet criteria for attention-deficit/hyperactivity disorder (ADHD) who do not have a mood disorder.

Design:

For children and adolescents with full or subthreshold DMDD, ADHD, and/or MDD, this study is an outpatient characterization and longitudinal follow-along design. Once determined to be eligible, individuals come for an initial assessment, and then return at varying intervals until age 25 for clinical interviews, behavioral tasks, structural and functional MRI, magnetoencephalography (MEG)/electroencephalography (EEG), and functional near-infrared spectroscopy (fNIRS).

For healthy volunteer children and adults this study is an outpatient cross-sectional study that includes clinical interviews, behavioral tasks, structural and functional MRI, magnetoencephalography (MEG)/electroencephalography (EEG), and functional near-infrared spectroscopy (fNIRS).

Outcome measures:

There are two primary outcome measures. First, this study will examine associations between irritability and clinical, behavioral, genetic, neuroanatomical, and neurophysiological variables in individuals with full or subthreshold DMDD and/or MDD, ADHD, anxiety, and healthy volunteers. Second, this study will examine between-group differences in clinical, behavioral, genetic, neuroanatomical, and neurophysiological variables in individuals with full or subthreshold DMDD and/or MDD, ADHD, anxiety, and healthy volunteers.

研究类型

观察性的

注册 (估计的)

2350

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

学习地点

    • Maryland
      • Bethesda、Maryland、美国、20892
        • 招聘中
        • National Institutes of Health Clinical Center
        • 接触:
          • For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
          • 电话号码:TTY dial 711 800-411-1222
          • 邮箱:ccopr@nih.gov

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

7年 至 85年 (孩子、成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

取样方法

非概率样本

研究人群

There are 6 separate populations being studied in this protocol: 1.Children and adolescents between the ages of 7-17 years old who meet criteria for DMDD or subthreshold DMDD. 2.Parents of children and adolescents, who meet criteria for DMDD or subthreshold DMDD and are enrolled in 02-M-0021, and are 25-85 years old will be studied. 3.Healthy volunteer children and adolescents between the ages of 7-17 years old. 4.Healthy volunteer adults between the ages of 18-25 years old. 5.Children and adolescents between the ages of 12-17 years old who meet criteria for major depressive disorder (MDD). 6.Children and adolescents between the ages of 8-17 years who meet criteria for attention-deficit /hyperactivity disorder (ADHD) who do not have a mood disorder.

描述

  • INCLUSION CRITERIA:

    1. Inclusion criteria for children with DMDD, subthreshold DMDD:

      1.1.1 Ages 7-17 at the time of recruitment; will be followed in the longitudinal component of the study until age 25.

      1.1.2 Abnormal mood (specifically, anger, sadness, and/or irritability), present at least half of the day most days (or at least half the day at least one day per week for subthreshold), and of sufficient severity to be noticeable by people in the child's environment (e.g. parents/caregivers, teachers, peers).

      1.1.3 Compared to his/her peers, the child exhibits markedly increased reactivity to negative emotional stimuli that is manifest verbally or behaviorally. For example, the child responds to frustration with extended temper tantrums (inappropriate for age and/or precipitating event), verbal rages, and/or aggression toward people or property. Such events occur, on average, at least three times a week. For subthreshold DMDD such tantrums occur on average at least once per month.

      1.1.4 The symptoms in # 1.1.2, and 1.1.3 above are currently present and have been present for at least 12 months without any symptom-free periods exceeding three months.

      1.1.5 The onset of symptoms must be prior to age 10 years.

      1.1.6 For DMDD the symptoms are severe in at least in one setting (e.g. violent outbursts, assaultiveness at home, school, or with peers) and at least mild (distractibility, intrusiveness) in a second setting. For subthreshold DMDD, there must be evidence of impairment causing distress to the child or to those around him/her in at least one setting.

    2. Caregivers of children and adolescents with DMDD or subthreshold DMDD enrolled in 02-M-0021

      2.1.1. Are capable of performing behavioral tasks and/or scanning.

      2.1.2. Speaks English

    3. Healthy Volunteer (Control) Children

      3.1.1. Control subjects will be group matched to the patients.

      3.1.2. Have an identified primary care physician.

      3.1.3. Speaks English

    4. Healthy Volunteer Adults

      4.1.1 Control subjects will be group matched to the patients.

      4.1.2. They will have normal physical and neurological examinations by history or checklist

      4.1.3. Have an identified primary care physician.

      4.1.4 Speaks English

    5. Children with Major Depressive Disorder (MDD) Inclusion criteria (all must be met):

      5.1.1 Ages 11-17 at the time of recruitment; will be followed in the longitudinal component of the study until age 25.

      5.1.2. DSM-IV or DSM-5 Major Depressive Disorder

      5.1.2.1 Five or more of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

      5.1.2.1.1 Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feeling sad, blue, "down in the dumps," or empty) or observation made by others (e.g., appears tearful or about to cry). (In children and adolescents, this may present as an irritable or cranky, rather than sad, mood.)

      5.1.2.1.2 Markedly diminished interest or pleasure in all, or almost all, activities every day, such as no interest in hobbies, sports, or other things the person used to enjoy doing.

      5.1.2.1.3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5 percent of body weight in a month), or decrease or increase in appetite nearly every day.

      5.1.2.1.4. Insomnia (inability to get to sleep or difficulty staying asleep) or hypersomnia (sleeping too much) nearly every day

      5.1.2.1.5. Psychomotor agitation (e.g., restlessness, inability to sit still, pacing, pulling at clothes or clothes) or retardation (e.g., slowed speech, movements, quiet talking) nearly every day

      5.1.2.1.6. Fatigue, tiredness, or loss of energy nearly every day (e.g., even the smallest tasks, like dressing or washing, seem difficult to do and take longer than usual).

      5.1.2.1.7. Feelings of worthlessness or excessive or inappropriate guilt nearly every day (e.g., ruminating over minor past failings).

      5.1.2.1.8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (e.g. appears easily distracted, complains of memory difficulties).

      5.1.2.1.9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideas without a specific plan, or a suicide attempt or a specific plan for committing suicide

      5.1.2.1.10 Symptoms cause clinically significant distress or impairment in social, occupational/academic, or other important areas of functioning.

      5.1.2.1.11. The episode is not attributable to the physiological effects of a substance or to another medical condition.

      5.1.3. Youth with MDD who are continuing in research as adults must also be receiving psychiatric care for their MDD, if it is ongoing

    6. Children with Attention-Deficit/Hyperactivity Disorder (ADHD)

6.1.1. Age 8-17

6.1.2. Currently meets DSM-IV or DSM-5 criteria for ADHD

6.1.3. Subjects with other primary psychiatric disorders including anxiety disorders, dysthymic disorder, past major depression, oppositional defiant disorder, tic disorders, and the learning, communication, and elimination disorders may be accepted

6.1.4. Have an identified primary care physician.

6.1.5. Speaks English

EXCLUSION CRITERIA:

1.3 Exclusion criteria for those with DMDD:

1.3.1 The individual exhibits any of these cardinal bipolar symptoms:

1.3.1.1 Elevated or expansive mood

1.3.1.2 Grandiosity or inflated self-esteem

1.3.1.3 Decreased need for sleep

1.3.1.4 Increase in goal-directed activity (this can result in the excessive involvement in pleasurable activities that have a high potential for painful consequences)

1.3.1.5. Has BD symptoms in distinct periods lasting more than 1 day.

1.3.2. Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, PDD, or PTSD.

1.3.3. IQ< 70

1.3.4. The symptoms are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.

1.3.5. Currently pregnant or lactating

1.3.6. Meets criteria for alcohol or substance abuse with the last three months

2. Exclusion of caregivers of children and adolescents with DMDD or subthreshold DMDD

2.1 Have an I.Q. < 70

2.2 Have any serious medical condition or condition that interferes with participation

3.2 Healthy Volunteer (Control) Children:

3.2.1. I.Q. < 70;

3.2.2. Any serious medical condition or condition that interferes with fMRI or MEG/EEG scanning, or fNIRS, pregnant or lactating;

3.2.3. Past or current diagnosis of any anxiety disorder (panic disorder, GAD, Separation Anxiety Disorder, Social Phobia), mood disorder (manic or hypomanic episode, major depression), OCD, PTSD, Conduct Disorder, psychosis, current suicidal ideation, Tourette Disorder, Autism Spectrum Disorder or ADHD.

3.2.4. Substance abuse within two months prior to study participation or present substance abuse

3.2.5. History of sexual abuse.

3.2.6. Parent or sibling with Bipolar Disorder, recurrent MDD, or any disorder with psychosis.

4.2 Healthy Volunteer Adults:

4.2.1. IQ< 70

4.2.2. Pregnant

4.2.3. Any past or current history of Bipolar Disorder (any manic or hypomanic episode), recurrent MDD, or any disorder with psychosis

5.3 Exclusion criteria for those with MDD:

5.3.1 The individual exhibits any of these cardinal bipolar symptoms:

5.3.1.1 Elevated or expansive mood

5.3.1.2 Grandiosity or inflated self-esteem

5.3.1.3 Decreased need for sleep

5.3.1.4 Increase in goal-directed activity (this can result in the excessive involvement in pleasurable activities that have a high potential for painful consequences)

5.3.1.5. Has BD symptoms in distinct periods lasting more than 1 day.

5.3.2. Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, PDD, or PTSD.

5.3.3. IQ< 70

5.3.4. The symptoms are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.

5.3.5. Currently pregnant or lactating

5.3.6. Meets criteria for alcohol or substance abuse with the last three months

6.2. Exclusion criteria for those with ADHD:

6.2.1. IQ<70

6.2.2. Pregnancy

6.2.3. Ongoing medical illness or neurological disorder other than ADHD

6.2.4. Any condition that would interfere with the participants' ability to perform research tasks

6.2.5. Current Major Depression

6.2.6. Any past or present manic or hypomanic episode

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 观测模型:COHORT
  • 时间观点:PROSPECTIVE

队列和干预

团体/队列
干预/治疗
Children/adolescents with ADHD

Children/adolescents with ADHD

Children/Adolescents with DMDD or subthreshold DMDD

Children/Adolescents with DMDD or subthreshold DMDD

Children/adolescents with MDD

Children/adolescents with MDD

Healthy volunteer adults

Healthy volunteer adults

Healthy volunteer children/adolescents

Healthy volunteer children/adolescents

Parents of children/adolescents with DMDD or subthreshold DMDD

Parents of children/adolescents with DMDD or subthresdhold DMDD

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
To examine between-group differences in clinical, behavioral, genetic, neuroanatomical, and neurophysiological variables
大体时间:20 years

Individuals with full or subthreshold DMDD and/or MDD, ADHD, anxiety (see protocol 00-M-0192), and healthy volunteers (see protocol 00-M-0198).

20 years
To examine associations between irritability and clinical, behavioral, genetic, neuroanatomical, and neurophysiological variables
大体时间:20 years

Individuals with full or subthreshold DMDD and/or MDD, ADHD, anxiety (see protocol 00-M-0192), and healthy volunteers (see protocol 00-M-0198).

20 years

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Melissa A Brotman, Ph.D.、National Institute of Mental Health (NIMH)

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2002年1月1日

研究注册日期

首次提交

2001年10月31日

首先提交符合 QC 标准的

2001年10月31日

首次发布 (估计的)

2001年11月1日

研究记录更新

最后更新发布 (实际的)

2026年9月23日

上次提交的符合 QC 标准的更新

2026年9月22日

最后验证

2026年9月21日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

不

IPD 计划说明

No individual participant data (IPD) will be shared.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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