2003 — 2007 |
Youngstrom, Eric A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Assessment of Juvenille Bipolar Spectrum Disorders @ Case Western Reserve University
DESCRIPTION (provided by applicant): Bipolar spectrum disorders (BPSD) are commonly misdiagnosed in community mental health settings, resulting in suboptimal treatment selection that can actually worsen the course of the disorder. Part of the difficulty in diagnosis is the current lack of consensus about the phenomenology of juvenile BPSD. At present, there also is no certainty about the base rate at which BPSD might present at a community mental health setting, nor is there an established set of instruments that could be used to screen a juvenile community sample for bipolar spectrum disorders. Such a screening protocol is sorely needed, given the long-term trajectory and serious consequences of untreated or mistreated BPSD, and the potential value of early intervention if juvenile cases could be identified. Preliminary evidence from this research group suggests that several measures perform well at distinguishing BPSD from unipolar depression, disruptive behavior disorders, and other disorders in children and adolescents (see Appendices). However, these findings were based on a sample presenting at an outpatient research clinic specializing in the treatment of juvenile mood disorders and psychopharmacology research. Thus, several factors prevent the immediate application of existing findings to a community setting, including the lack of soundly-established base rate of BPSD at community- based mental health centers, the unknown effects of potential ascertainment bias at a mood disorders clinic versus a community setting, changes in demographics or other sample characteristics that might interact with test performance, and the fact that test performance might degrade when exported from a research framework into a community context - much as therapeutic efficacy estimates usually exceed effectiveness findings. The purpose of the proposed study is to develop effective means of screening for bipolar spectrum disorders in a community mental health setting serving an ethnically and racially diverse population. This will be accomplished by determining the prevalence of bipolar disorders in a community sample, validating measures that have performed well in an academic clinical setting, and clarifying the features of early presentation of bipolar spectrum disorders along with their longitudinal course over 18 months. Particular attention is paid to identifying and validating diagnostic characteristics of youths with bipolar symptoms that do not meet full criteria for a bipolar diagnosis. These children, currently labeled "Bipolar- Not Otherwise Specified", may represent an early developmental precursor of later bipolar disorder, or they may manifest a developmentally different presentation and course.
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0.924 |
2008 |
Youngstrom, Eric |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Fronto-Limbic Brain of Bipolar Children and Adolescents @ University of North Carolina Chapel Hill
Abnormalities in fronto-limbic brain (FLB) regions involved in mood regulation have been associated with bipolar disorder (BD) in neuroimaging studies on adults. Did these FLB changes develop as BD progressed, or did they emerge early during BD development? The latter would suggest that (1) developmental abnormalities in brain maturation processes may have led to these FLB changes. And, if so, then (2) treatments that reduced or alleviated these brain changes early in the disease process might reduce the severity of BD. To test these hypotheses, we will conduct a combined in vivo neuroimaging and clinical intervention trial in post-pubertal adolescents (ages 12-17 years old) who have BD (BD adolescents), that will examine the relationships between (a) FLB abnormalities, (b) BD progression and severity, and (c) response to a mood-stabilizing medication (valproate). We will study 60 untreated BD adolescents and 60 matched healthy controls. 30 BD patients will not have comorbid attention deficit hyperactive disorder (ADHD), oppositional defiant disorder (ODD), and/or conduct disorder (CD), while another 30 will have these comorbid conditions. Patients in both groups may also have comorbid anxiety disorders, with the exception of obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). The 60 patients will enter a 6-week open trial with valproate at therapeutic doses (as measured by serum valproate levels). Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) will be performed to compare brain anatomy (size of key FLB regions involved in mood regulation, with a focus on prefrontal cortex and amygdala) and neurochemistry (levels of N-acetyl aspartate (NAA), a non-specific marker of neuronal viability or function) across the 3 groups, as well as after treatment. Neuropsychological testing will also be conducted to evaluate specific FLB functions. This will be the first in vivo evaluation of FLB abnormalities in BD adolescents and in their response to treatment. It will contribute to elucidating the pathophysiologic mechanisms of BD, to understanding the mechanisms of action of mood stabilizers, and to identifying new endophenotypes of BD or biological targets that could aid in diagnosis, monitoring or treatment.
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0.915 |