Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder
|Official Title:||Characterization and Pathophysiology of Severe Mood and Behavioral Dysregulation in Children and Youth|
|Study Start Date:||October 29, 2001|
The past decade has seen a dramatic increase in focus on pediatric bipolar disorder (BD), as the number of children receiving the diagnosis has escalated . Discussion has centered on the diagnostic boundaries of bipolar disorder, and whether nonepisodic severe irritability is a developmental presentation of mania. Beginning in 2002, our work defined a specific phenotype [severe mood dysregulation (SMD)] including youth with chronic angry mood with behavioral outbursts and hyperarousal symptoms. The purpose of this work has been to examine similarities and differences between youth with BD and SMD, and address the nosological question of whether the diagnosis of BD should be separated from a chronic angry mood with behavioral outbursts and hyperarousal symptoms similar to those present in children and adolescents with attention deficit hyperactivity disorder (ADHD). Before this work began, there was substantial debate, with little evidence to support either position.
Over the last decade, there has been substantial progress suggesting these might be best viewed a separate conditions, but important questions remain. In 2013 the Diagnostic and Statistical Manual (DSM) added Disruptive Mood Dysregulation Disorder, (DMDD) that is very similar to SMD in that it shares features of severe irritability. Future work needs to address the relationship between classic presentations of BD (as in protocol 00-M-0198) and SMD, as defined in this protocol or DMDD as defined in the DSM. Data suggest that there is a strong likelihood for those DMDD/SMD in youth to develop Major Depression. Thus, youth with Major Depressive Disorder (MDD) (with and without prior DMDD) are an important comparison group. We are examining the developmental trajectory, phenomenology, behavioral correlates, and underlying neural mechanisms of chronic irritability and MDD in youth. Our overall goal is to gain a clearer understanding of the course and neurophysiology these disorders to inform treatment and improve the outcome for children with irritability and depression. In order to advance this aim this protocol has 3 objectives:
- to use longitudinal techniques to characterize the clinical and physiological manifestations of irritability in youth with SMD or DMDD, and in youth who are significantly irritable yet fall short of fully meeting criteria (and thus are subthreshold for DMDD).
- to identify and follow longitudinally behavioral, neuropsychological, neurophysiological, and neuroanatomical correlates of DMDD, and compare them to pediatric disorders that bear some similarities (BD, and attention deficit hyperactivity disorder (ADHD), MDD, subthreshold DMDD) and to typically developing youth.
- to examine genetic and familial correlates of full and sub-threshold SMD,DMDD, and MDD.
B. Study population:
There are 4 separate populations being studied in this protocol:
- Children and adolescents between the ages of 7-17 years old who meet criteria for SMD or DMDD or subthreshold DMDD.
- Healthy volunteer children and adolescents between the ages of 7-17 years old
- Healthy volunteer adults between the ages of 18-25 years old.
- Children and adolescents between the ages of 12-17 years old who meet criteria for major depressive disorder (MDD)
For children and adolescents with SMD or full or subthreshold DMDD 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 1-2-year 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.
This study will examine between-group differences in clinical, behavioral, genetic, neuroanatomical, and neurophysiological variables in individuals with SMD or full or subthreshold DMDD and/or MDD, BD (BD, see protocol 00-M-0198), and healthy volunteers.
Children with SMD or full or subthreshold DMDD and/or MDD may also be compared on these features to those with other disorders (e.g. anxiety, depression) who are studied under Dr. Daniel Pine s protocol 01-M-0192 in order to elucidate differences between SMD or DMDD and these conditions.
Longitudinal clinical, behavioral, and neuroanatomical data will also be obtained.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00025935
|Contact: Ellen Leibenluft, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Ellen Leibenluft, M.D.||National Institute of Mental Health (NIMH)|