Neuroimaging of Children at Risk for Biopolar Disorder

Summary

Principal Investigator: K D Chang
Abstract: DESCRIPTION (provided by the applicant): The long-term objective of this Mentored Patient-Oriented Research Career Development (K23) Award is to develop the candidate's skills in patient-oriented clinical research so that he may become an independent researcher in the field of child mental health. Dr. Chang's specific goal is to gain proficiency in pediatric mood disorders research, specifically in the area of utilizing brain imaging techniques to elucidate neurobiological data correlated to clinical presentations of children and adolescents with bipolar disorder (BD). To accomplish this goal, the candidate will be mentored by experts in the field of neuroimaging, childhood and adult BD, and statistics and research design. The candidate furthermore will participate in educational activities in his department as well as formal coursework in the areas of cognitive neuroscience, brain imaging, and statistics. Finally, the candidate will carry out a research project closely aligned with his research training plan. The goal of the proposed research project is to gather longitudinal phenomenological and brain imaging data on child and adolescent offspring of parents with BD, who are at high risk for developing bipolar disorder. These at-risk children, some already with BD, and healthy controls will be assessed longitudinally over three years by brain functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (MRS). fMRI tasks will be related to emotion and attention, and proton MRS will be of bilateral dorsolateral prefrontal cortices (DLPFC), specifically assessing n-acetyl aspartate/creatinine (NAA/Cr) ratios. Phenomenology will be assessed through structured diagnostic interviews, clinician-rated scales, and patient-rated questionnaires. We hypothesize that (1) at-risk offspring already with BD at baseline will have differing areas of activation and deactivation than healthy controls, primarily in DLPFC and anterior cingulate cortex (ACC), (2) at-risk offspring with BD will have lower NAA/Cr ratios in bilateral DLPFC compared to healthy controls, and (3) at-risk offspring who develop BD in the course of this study will demonstrate a greater decrease in DLPFC NAA/Cr from baseline than controls and patterns of brain activation similar to those subjects already with BD, either at baseline or at three-year follow-up. Through conducting this research project and implementation of the research training plan, Dr. Chang plans to become an independent investigator in the field of pediatric BD and thus contributing to the current knowledge of the neurobiology and development of BD.
Funding Period: 2001-12-12 - 2006-11-30
more information: NIH RePORT

Top Publications

  1. ncbi Deformations of amygdala morphology in familial pediatric bipolar disorder
    Ryan Kelley
    Center for Interdisciplinary Brain Sciences Research CIBSR, Stanford University School of Medicine, Palo Alto, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, USA
    Bipolar Disord 15:795-802. 2013
  2. pmc Prospective neurochemical characterization of child offspring of parents with bipolar disorder
    Manpreet K Singh
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, USA Electronic address
    Psychiatry Res 214:153-60. 2013
  3. pmc Abnormal amygdala and prefrontal cortex activation to facial expressions in pediatric bipolar disorder
    Amy S Garrett
    Center for Interdisciplinary Brain Sciences Research and the Pediatric Bipolar Disorders Program at Stanford University School of Medicine, Stanford, CA 94305 5719, USA
    J Am Acad Child Adolesc Psychiatry 51:821-31. 2012
  4. pmc Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder
    Asya Karchemskiy
    Center for Interdisciplinary Brain Sciences Research, Stanford University Department of Psychiatry, Stanford, CA, United States
    Psychiatry Res 194:319-25. 2011
  5. pmc Brain glutamatergic characteristics of pediatric offspring of parents with bipolar disorder
    Manpreet Singh
    Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, USA
    Psychiatry Res 182:165-71. 2010
  6. ncbi Striatal volumes in pediatric bipolar patients with and without comorbid ADHD
    Isabelle Yisha Liu
    Washington University School of Medicine, Saint Louis, MO, USA
    Psychiatry Res 194:14-20. 2011
  7. pmc Neural correlates of response inhibition in pediatric bipolar disorder
    Manpreet K Singh
    Pediatric Bipolar Disorders Program, Stanford University School of Medicine, Stanford, California 94305 5719, USA
    J Child Adolesc Psychopharmacol 20:15-24. 2010
  8. pmc Subcortical volumetric correlates of anxiety in familial pediatric bipolar disorder: a preliminary investigation
    Diana I Simeonova
    Pediatric Bipolar Disorders Program, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305 5540, USA
    Psychiatry Res 173:113-20. 2009
  9. ncbi Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a tract-based spatial statistics analysis
    Naama Barnea-Goraly
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Center for Interdisciplinary Brain Sciences Research, Stanford University, 401 Quarry Road, MC 5795, Stanford, CA 94305 5795, USA
    Biol Psychiatry 66:238-44. 2009
  10. pmc Effect of divalproex on brain morphometry, chemistry, and function in youth at high-risk for bipolar disorder: a pilot study
    Kiki Chang
    Division of Child and Adolescent Psychiatry, Stanford University School of Medicine, Stanford, California 94305 5540, USA
    J Child Adolesc Psychopharmacol 19:51-9. 2009

Scientific Experts

  • K D Chang
  • Manpreet K Singh
  • Naama Barnea-Goraly
  • Asya Karchemskiy
  • Meghan Howe
  • Diana I Simeonova
  • Ryan Kelley
  • Dylan Alegria
  • Amy Garrett
  • Allan Reiss
  • Allan L Reiss
  • Amy S Garrett
  • Isabelle Yisha Liu
  • Nancy Adleman
  • Fiona M Baumer
  • Kim A Gallelli
  • Paul Thompson
  • Ryan G Kelley
  • Nancy E Adleman
  • Meghan E Howe
  • Valerie Jackson
  • Ashraf Attalla
  • Kim Gallelli
  • Diana Iorgova Simeonova
  • Joachim Hallmayer
  • Daniel Spielman
  • Connie Strong
  • Terence A Ketter
  • Christopher M Wagner

Detail Information

Publications17

  1. ncbi Deformations of amygdala morphology in familial pediatric bipolar disorder
    Ryan Kelley
    Center for Interdisciplinary Brain Sciences Research CIBSR, Stanford University School of Medicine, Palo Alto, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, USA
    Bipolar Disord 15:795-802. 2013
    ..Whether smaller amygdalar volume is a consequence or antecedent of the first episode of mania is not known. Additionally, smaller volume has not been localized to specific amygdala subregions...
  2. pmc Prospective neurochemical characterization of child offspring of parents with bipolar disorder
    Manpreet K Singh
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, USA Electronic address
    Psychiatry Res 214:153-60. 2013
    ..It may be the case that with intervention youth at risk for BD are normalizing otherwise potentially aberrant neurochemical trajectories in the DLPFC. A longer period of follow-up may be required before observing any group differences. ..
  3. pmc Abnormal amygdala and prefrontal cortex activation to facial expressions in pediatric bipolar disorder
    Amy S Garrett
    Center for Interdisciplinary Brain Sciences Research and the Pediatric Bipolar Disorders Program at Stanford University School of Medicine, Stanford, CA 94305 5719, USA
    J Am Acad Child Adolesc Psychiatry 51:821-31. 2012
    ..The current study investigates whether these differences are associated with the early or late phase of activation, suggesting different temporal characteristics of brain responses...
  4. pmc Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder
    Asya Karchemskiy
    Center for Interdisciplinary Brain Sciences Research, Stanford University Department of Psychiatry, Stanford, CA, United States
    Psychiatry Res 194:319-25. 2011
    ..Longitudinal studies are needed to determine whether amygdalar volumes change during and after the development of BD...
  5. pmc Brain glutamatergic characteristics of pediatric offspring of parents with bipolar disorder
    Manpreet Singh
    Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, USA
    Psychiatry Res 182:165-71. 2010
    ..Longitudinal studies are necessary to confirm whether prefrontal glutamate decreases only after the onset of full mania...
  6. ncbi Striatal volumes in pediatric bipolar patients with and without comorbid ADHD
    Isabelle Yisha Liu
    Washington University School of Medicine, Saint Louis, MO, USA
    Psychiatry Res 194:14-20. 2011
    ..Thus, the presence or absence of comorbid ADHD in patients with BD was associated with distinct alterations in caudate volumes, suggesting that these groups have different, but related, mechanisms of neuropathology...
  7. pmc Neural correlates of response inhibition in pediatric bipolar disorder
    Manpreet K Singh
    Pediatric Bipolar Disorders Program, Stanford University School of Medicine, Stanford, California 94305 5719, USA
    J Child Adolesc Psychopharmacol 20:15-24. 2010
    ..We aimed to examine response inhibition in this population, as an element of executive function, which, if aberrant, may interfere with learning and information processing...
  8. pmc Subcortical volumetric correlates of anxiety in familial pediatric bipolar disorder: a preliminary investigation
    Diana I Simeonova
    Pediatric Bipolar Disorders Program, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305 5540, USA
    Psychiatry Res 173:113-20. 2009
    ..The overlap between anxiety and familial pediatric BD suggests that anxiety may be one important area of future research in parsing out the heterogeneous nature and complex etiology of early-onset BD...
  9. ncbi Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a tract-based spatial statistics analysis
    Naama Barnea-Goraly
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Center for Interdisciplinary Brain Sciences Research, Stanford University, 401 Quarry Road, MC 5795, Stanford, CA 94305 5795, USA
    Biol Psychiatry 66:238-44. 2009
    ..In this study, we investigated white matter structure in adolescents with familial bipolar disorder using diffusion tensor imaging (DTI) and a whole brain analysis...
  10. pmc Effect of divalproex on brain morphometry, chemistry, and function in youth at high-risk for bipolar disorder: a pilot study
    Kiki Chang
    Division of Child and Adolescent Psychiatry, Stanford University School of Medicine, Stanford, California 94305 5540, USA
    J Child Adolesc Psychopharmacol 19:51-9. 2009
    ..We sought to examine the effects of divalproex on the structure, chemistry, and function of specific brain regions in children at high-risk for BD...
  11. ncbi Adult bipolar disorder is continuous with pediatric bipolar disorder
    Kiki Chang
    Pediatric Bipolar Disorders Program, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Lucile Packard Children s Hospital, California 94305 5540, USA
    Can J Psychiatry 52:418-25. 2007
    ..Prospective studies incorporating phenomenological and biological assessment are needed to decisively address this issue...
  12. ncbi Will neuroimaging ever be used to diagnose pediatric bipolar disorder?
    Kiki Chang
    Stanford University School of Medicine, CA 94305 5540, USA
    Dev Psychopathol 18:1133-46. 2006
    ....
  13. ncbi A pilot study of antidepressant-induced mania in pediatric bipolar disorder: Characteristics, risk factors, and the serotonin transporter gene
    Fiona M Baumer
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305 5540, USA
    Biol Psychiatry 60:1005-12. 2006
    ..We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD...
  14. ncbi N-acetylaspartate levels in bipolar offspring with and at high-risk for bipolar disorder
    Kim A Gallelli
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
    Bipolar Disord 7:589-97. 2005
    ..To address this question, we used proton magnetic resonance spectroscopy ((1)H-MRS) to compare DLPFC levels of NAA among bipolar offspring with early-onset BD, bipolar offspring with subsyndromal symptoms of BD and healthy children...
  15. ncbi Creativity in familial bipolar disorder
    Diana I Simeonova
    Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Stanford University School of Medicine, Stanford, CA 94305 5540, USA
    J Psychiatr Res 39:623-31. 2005
    ....
  16. ncbi Cortical magnetic resonance imaging findings in familial pediatric bipolar disorder
    Kiki Chang
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
    Biol Psychiatry 58:197-203. 2005
    ..We studied gray matter volume, ventricular-to-brain ratios (VBR), and number of WMH in patients with familial, pediatric BD compared with control subjects...
  17. ncbi Reduced amygdalar gray matter volume in familial pediatric bipolar disorder
    Kiki Chang
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 5540, USA
    J Am Acad Child Adolesc Psychiatry 44:565-73. 2005
    ..We sought to study morphometric characteristics of these structures in pediatric subjects with familial BD compared with healthy controls...