New Insights into PKU and the Brain Shawn Christ, Ph.D. Assoc - - PowerPoint PPT Presentation
New Insights into PKU and the Brain Shawn Christ, Ph.D. Assoc Director, Brain Imaging Center Asst Professor, Dept of Psych Sciences University of Missouri Disclosure: On occasion, I also serve as an outside consultant for BioMarin
Assoc Director, Brain Imaging Center Asst Professor, Dept of Psych Sciences University of Missouri
Disclosure: On occasion, I also serve as an outside consultant for BioMarin Pharmaceutical Inc., and they are funding some of our current research on PKU and BH4.
The help & support of individuals and families such as you makes our work possible.
http://clinicalneurolab.missouri.edu/Vancouver2012.pdf
prefrontal cortex dopamine pathways frontal lobe
Thinking Skills, Emotions, & Behavior Brain Disruption Disruption of Dopamine System PAH Deficiency
Past & Current Treatment Patient Environment & Resources Christ (in prep)
Thinking Skills, Emotions, & Behavior PAH Deficiency
Past & Current Treatment
19% 16% 5% 5% 1% 37% 31% 14% 14% 6% 10 20 30 40 50
Depressed Mood Phobias Generalized Anxiety Hypochondriac Worries Anxiety at Work % of Individuals Reporting Problems
Non-PKU (n = 181) PKU (n = 35 Pietz et al. (1997)
Brain Disruption PAH Deficiency
Complex behavior relies on a
host of underlying processes that are each carried out in a single region of brain. In
behavior relies on a network
Anderson & Leuzzi (2010)
Anderson & Leuzzi (2010)
Peng, Peck, White & Christ (in press)
Peng, Peck, White & Christ (in press)
How well do spatially distinct regions work together to support complex cognitive functions? Are the physical brain regions and/or their connections damaged or otherwise atypical?
Brain Disruption PAH Deficiency Thinking Skills, Emotions, & Behavior
Christ, S. E., Moffitt, A., & Peck, D. (2010). Disruption of prefrontal function and connectivity in individuals with phenylketonuria. Molecular Genetics & Metabolism, 99, S33-40.
Christ et al. (2010)
Christ et al. (2010)
Christ et al. (2010)
z = 51 z = 50 z = 0
Christ et al. (2010)
Evaluated by looking at the degree of concordance
Disrupted in several other clinical populations:
Strength of functional connectivity positively
Christ et al. (2010)
z = 53 z = 33
Left SFG Left IFG
Christ et al. (2010)
Christ et al. (2010)
from Fox et al. (2005)
From Buckner & Carroll (2007)
Christ et al. (JIMD, 2012)
Christ et al. (JIMD, 2012)
How well do spatially distinct regions work together to support complex cognitive functions? Are the physical connections (pathways) between regions damaged or otherwise atypical?
How well do spatially distinct regions work together to support complex cognitive functions? Are the physical connections (pathways) between regions damaged or otherwise atypical?
Shawn Christ christse@missouri.edu http://clinicalneurolab.missouri.edu