The principle aim of this career development plan is to provide the candidate with the training, support, and resources required to develop as in independent investigator in the field of neuropsychiatric research. The candidate's long-term goals are to advance the knowledge of the developmental neuropathology of bipolar disorder by establishing a multidisciplinary research program that combines clinical (psychosocial and pharmacologic), developmental, and neuroimaging methods. The candidate's short-term goals for the duration of this award are to develop expertise in the following areas: (1) methods, design and analysis of multimodal (structural and functional) MRI studies;(2) cognitive neuroscience and neuropsychology;(3) research on the normal and abnormal developmental of brain networks. These training goals will be met through a combined program of coursework, consultation with established research scientists in these fields, and completion of a research study at the University of Utah's Brain Institute. The design and hypotheses of the proposed study were based on a growing body of work (including the candidate's prior research) indicating that bipolar disorder is a developmental brain disorder whose pathophysiology is associated with aberrant maturation of brain networks. Complicating the early-onset bipolar literature is the inclusion of high rates of youths with comorbid ADHD making it difficult to determine whether the neuroanatomical correlates are associated with bipolar disorder, attention-deficit/hyperactivity disorder (ADHD) or both disorders. Accordingly, the research plan proposes to evaluate a specific resting-state network (the default mode network) in 2 groups of adolescence: bipolar disorder without comorbid attention-deficit/hyperactivity disorder (ADHD) and healthy youths. This study will utilize a multimodal approach incorporating 2 types of neuroimaging techniques shown to measure brain connectivity: functional MRI and diffusion tensor imaging. The first major aim of this study is to examine the structural and functional connectivity of the default mode network in healthy adolescents. The second major aim of this study is to determine if these two complementary neuroimaging techniques can detect distinct differences in the default mode network between psychiatrically healthy youths and those with bipolar disorder without comorbid ADHD. This information will provide the foundation for future longitudinal investigations regarding the normal and abnormal development of this network.

Public Health Relevance

The results of this study are expected to increase our understanding of the maturation of brain networks in adolescence, which has been a relatively under-studied area despite its potential relevance to bipolar disorder and other neuropsychiatric disorders. In addition this study has relevance to the pathophysiology and phenomenology of bipolar disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH087831-03
Application #
8267731
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Sarampote, Christopher S
Project Start
2010-08-01
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
3
Fiscal Year
2012
Total Cost
$184,864
Indirect Cost
$13,331
Name
University of Utah
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Lopez-Larson, Melissa Patricia; Rogowska, Jadwiga; Yurgelun-Todd, Deborah (2015) Aberrant orbitofrontal connectivity in marijuana smoking adolescents. Dev Cogn Neurosci 16:54-62
Lopez-Larson, Melissa; King, Jace B; McGlade, Erin et al. (2013) Enlarged thalamic volumes and increased fractional anisotropy in the thalamic radiations in veterans with suicide behaviors. Front Psychiatry 4:83
Churchwell, John C; Lopez-Larson, Melissa; Yurgelun-Todd, Deborah A (2012) Orbitofrontal cortex and neuromaturation: a gateway to risk? Biol Psychiatry 71:664-5
Lopez-Larson, Melissa P; Rogowska, Jadwiga; Bogorodzki, Piotr et al. (2012) Cortico-cerebellar abnormalities in adolescents with heavy marijuana use. Psychiatry Res 202:224-32
Lopez-Larson, Melissa Patricia; King, Jace Bradford; Terry, Janine et al. (2012) Reduced insular volume in attention deficit hyperactivity disorder. Psychiatry Res 204:32-9
Lopez-Larson, Melissa P; Anderson, Jeffrey S; Ferguson, Michael A et al. (2011) Local brain connectivity and associations with gender and age. Dev Cogn Neurosci 1:187-97
Yurgelun-Todd, Deborah A; Bueler, C Elliott; McGlade, Erin C et al. (2011) Neuroimaging correlates of traumatic brain injury and suicidal behavior. J Head Trauma Rehabil 26:276-89
Anderson, J S; Dhatt, H S; Ferguson, M A et al. (2011) Functional connectivity targeting for deep brain stimulation in essential tremor. AJNR Am J Neuroradiol 32:1963-8
Anderson, Jeffrey S; Ferguson, Michael A; Lopez-Larson, Melissa et al. (2011) Connectivity gradients between the default mode and attention control networks. Brain Connect 1:147-57
Anderson, J S; Ferguson, M A; Lopez-Larson, M et al. (2011) Reproducibility of single-subject functional connectivity measurements. AJNR Am J Neuroradiol 32:548-55

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