Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00025935
Status:
RECRUITING
Last Update Posted:
2024-07-12
First Post:
2001-10-31
Brief Title:
Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Characterization and Pathophysiology of Severe Mood and Behavioral Dysregulation in Children and Youth
Status:
RECRUITING
Status Verified Date:
2024-09-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
Detailed Description:
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-DeficitHyperactivity 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 trust-worthiness 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 such as the COVID-19 pandemic 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 Parents of children and adolescents who meet criteria for DMDD or subthreshold DMDD and are enrolled in 02-M-0021 and are 25 - 59 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 ages of 8-17 years who meet criteria for attention-deficithyperactivity disorder ADHD who do not have a mood disorder
Design
For children and adolescents with full or subthreshold DMDD andor 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 and structural and functional MRI
For healthy volunteer children adults and parents of healthy volunteer children this study is an outpatient cross-sectional study that includes clinical interviews behavioral tasks and structural and functional MRI
For all individuals genetic material from saliva or blood is obtained under protocol 01-M-0254
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 andor 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 andor MDD ADHD anxiety and healthy volunteers
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-DeficitHyperactivity 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 trust-worthiness 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 such as the COVID-19 pandemic 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 Parents of children and adolescents who meet criteria for DMDD or subthreshold DMDD and are enrolled in 02-M-0021 and are 25 - 59 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 ages of 8-17 years who meet criteria for attention-deficithyperactivity disorder ADHD who do not have a mood disorder
Design
For children and adolescents with full or subthreshold DMDD andor 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 and structural and functional MRI
For healthy volunteer children adults and parents of healthy volunteer children this study is an outpatient cross-sectional study that includes clinical interviews behavioral tasks and structural and functional MRI
For all individuals genetic material from saliva or blood is obtained under protocol 01-M-0254
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 andor 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 andor MDD ADHD anxiety and healthy volunteers
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-M-0021 | None | None | None |