Bipolar Disorder (BPD) may be as common among youths as it is among adults. The lifetime prevalence for Bipolar Disorder in adults ranges from 0.6% to 1.1%. Determining biological markers for mania in children with BPD is important in order to further our understanding of the underlying pathology of BPD in children. Significant glutamatergic dysfunction is associated with BPD, and many medications that are effective in the treatment of BPD may do so through engagement at various points in the glutamate neurotransmitter system. In addition, persuasive post-mortem evidence exists of frontal cortex glial and neuronal abnormalities in BPD. These abnormalities may be present in children with BPD.
The aims of this study are to 1: establish an association between anterior cingulate cortex (ACC) glutamine and glutamate levels, and mania in children and adolescents with BPD;2: investigate how the atypical antipsychotic risperidone interacts with ACC glutamine and glutamate in children and adolescents with BPD. We propose to study 60 unmedicated manic children and adolescents with BPD (Bipolar 1 Disorder, the narrow phenotype;Young Mania Rating Scale (YMRS) >15) before and after treatment with risperidone. In addition, 60 age and sex matched healthy comparison children (HCS) will participate. Glutamate and glutamine levels will be measured in the ACC and occipital cortex (OC) using Proton Magnetic Resonance Spectroscopy (1H MRS) at 4.0 T. A baseline MRS scan will be acquired from the unmedicated subjects with BPD prior to commencing risperidone treatment. Following 6 weeks of risperidone treatment the subjects with BPD will have a follow up 4.0 T MRS scan. The healthy comparison children will also have two MRS scans 6 weeks apart. Manic symptoms will be assessed prior to each MRS examination using the YMRS. We hypothesize that (a) the mania associated with pediatric BPD is a consequence of glutamatergic abnormalities manifested by reduced ACC glutamine and glutamate and;(b) risperidone will raise ACC glutamine and glutamate levels in children with BPD who are risperidone responders (a 30 % decrease in YMRS). Looking directly at the glutamine and glutamate resonances will allow the assessment of mania biochemically. This project will lay groundwork for further studies to test novel interventions that may be anti-manic agents and suitable for use in a pediatric population. We are proposing to use technology based on MRI to determine if brain frontal cortex levels of the amino acid glutamate, and its precursor glutamine, may be used as potential markers for pediatric mania. In addition, we will look at the effects of the atypical antipsychotic risperidone on glutamate, glutamine and mania in children with bipolar disorder. We believe this work will lay groundwork for further studies to test novel interventions that may be anti-manic agents and suitable for use in a pediatric population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH073998-04
Application #
8136009
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Grabb, Margaret C
Project Start
2008-06-11
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
4
Fiscal Year
2011
Total Cost
$359,794
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Psychiatry
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
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Atagün, Murat ?lhan; ??ko?lu, Elif Muazzez; Soykan, Ça?lar et al. (2017) Perisylvian GABA levels in schizophrenia and bipolar disorder. Neurosci Lett 637:70-74
Henninger, Nils; Bouley, James; Sikoglu, Elif M et al. (2016) Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1. Brain 139:1094-105
Cochran, David M; Sikoglu, Elif M; Hodge, Steven M et al. (2015) Relationship among Glutamine, ?-Aminobutyric Acid, and Social Cognition in Autism Spectrum Disorders. J Child Adolesc Psychopharmacol 25:314-22
Sikoglu, Elif M; Liso Navarro, Ana A; Czerniak, Suzanne M et al. (2015) Effects of Recent Concussion on Brain Bioenergetics: A Phosphorus-31 Magnetic Resonance Spectroscopy Study. Cogn Behav Neurol 28:181-7
Czerniak, Suzanne M; Sikoglu, Elif M; Liso Navarro, Ana A et al. (2015) A resting state functional magnetic resonance imaging study of concussion in collegiate athletes. Brain Imaging Behav 9:323-32
Atagün, M I; ??ko?lu, E M; Can, S S et al. (2015) Investigation of Heschl's gyrus and planum temporale in patients with schizophrenia and bipolar disorder: a proton magnetic resonance spectroscopy study. Schizophr Res 161:202-9
Sikoglu, Elif M; Navarro, Ana A Liso; Starr, Debra et al. (2015) Vitamin D3 Supplemental Treatment for Mania in Youth with Bipolar Spectrum Disorders. J Child Adolesc Psychopharmacol 25:415-24
Liso Navarro, Ana A; Sikoglu, Elif M; Heinze, Cailin R et al. (2014) Effect of diet on brain metabolites and behavior in spontaneously hypertensive rats. Behav Brain Res 270:240-7

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