In recent years, there has been increased recognition of adolescent major depressive disorder (MDD) as a severe, highly prevalent and chronically disabling disorder. By most measures, adolescent MDD is continuous with adult MDD, including clinical course, secular trends, and psychobiologic correlates. Studies of the illness during adolescence can, therefore, clarify the contribution of neurodevelopmental abnormalities to the pathogenesis of the disorder. Neurobiological models for MDD have consistently implicated temporo-limbic, prefrontal cortical and basal ganglia circuits in the pathophysiology of the disorder. Strikingly, children and adolescents with MDD have been largely overlooked in brain imaging studies. In particular, there are no published studies using magnetic resonance spectroscopy (MRS) to investigate brain chemistry in depressed children and adolescents. Yet the inclusion of children and adolescents in these types of studies is critical in order to determine whether abnormalities in brain chemistry in depressed patients are the consequence of altered development over the life span, or if they are present even early in development thus representing a risk factor for subsequent development of depression. Preliminary studies by the applicants using MRS suggest increased caudate and anterior cingulate choline concentrations in psychotropic-naive pediatric MDD patients compared to age and sex matched controls. No differences in choline levels were observed between MDD patients and controls in occipital cortex choline levels. Pilot studies showed reductions in caudate but not occipital choline concentrations after 12 weeks of effective monotherapy with the selective serotonin reuptake inhibitor (SSRI) paroxetine. In this project, proton MRS will be used for the direct, in vivo and noninvasive evaluation and comparison of the impact of paroxetine vs. cognitive behavioral therapy (CBT) on brain chemistry as related to treatment efficacy in adolescents with MDD. Such an approach will help 1) determine whether psychotropic-naive adolescents with MDD differ from healthy controls in neurochemistry and 2) determine whether effective treatment with paroxetine and CBT results in localized and treatment-specific changes in brain chemistry. An understanding of the neurochemical disturbances in MDD may be important for the development of new treatment approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH065122-03
Application #
6649185
Study Section
Special Emphasis Panel (ZRG1-BDCN-5 (01))
Program Officer
Rumsey, Judith M
Project Start
2001-08-16
Project End
2006-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
3
Fiscal Year
2003
Total Cost
$298,000
Indirect Cost
Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Fallucca, Erin; MacMaster, Frank P; Haddad, Joseph et al. (2011) Distinguishing between major depressive disorder and obsessive-compulsive disorder in children by measuring regional cortical thickness. Arch Gen Psychiatry 68:527-33
MacMaster, Frank P; Rosenberg, David R (2010) THE USE OF GLUTAMATE MODULATING DRUGS IN OBSESSIVE COMPULSIVE DISORDER. Child Adolesc Psychopharmacol News 15:1-5
MacMaster, Frank P; Rosenberg, David R (2010) NEUROBIOLOGICAL EVIDENCE SUPPORTING GLUTAMATE'S ROLE IN PEDIATRIC OBSESSIVE COMPULSIVE DISORDER. Child Adolesc Psychopharmacol News 15:6-10
Chen, Hua-Hsuan; Rosenberg, David R; MacMaster, Frank P et al. (2008) Orbitofrontal cortex volumes in medication naive children with major depressive disorder: a magnetic resonance imaging study. J Child Adolesc Psychopharmacol 18:551-6
MacMaster, Frank P; O'Neill, Joseph; Rosenberg, David R (2008) Brain imaging in pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 47:1262-72
Szeszko, Philip R; Christian, Christopher; Macmaster, Frank et al. (2008) Gray matter structural alterations in psychotropic drug-naive pediatric obsessive-compulsive disorder: an optimized voxel-based morphometry study. Am J Psychiatry 165:1299-307
Matsuo, Koji; Rosenberg, David R; Easter, Philip C et al. (2008) Striatal volume abnormalities in treatment-naive patients diagnosed with pediatric major depressive disorder. J Child Adolesc Psychopharmacol 18:121-31
MacMaster, Frank P; Moore, Gregory J; Russell, Aileen et al. (2008) Medial temporal N-acetyl-aspartate in pediatric major depression. Psychiatry Res 164:86-9
MacMaster, Frank P; Mirza, Yousha; Szeszko, Philip R et al. (2008) Amygdala and hippocampal volumes in familial early onset major depressive disorder. Biol Psychiatry 63:385-90
Gilbert, Andrew R; Keshavan, Matcheri S; Diwadkar, Vaibhav et al. (2008) Gray matter differences between pediatric obsessive-compulsive disorder patients and high-risk siblings: a preliminary voxel-based morphometry study. Neurosci Lett 435:45-50

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