understanding schizophrenia risk: emerging genetics and ... · 11/3/2017 · understanding...
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Beth Stevens
F.FM Kirby Neurobiology Center
Boston Children’s Hospital, HMS
Broad Institute
Understanding Schizophrenia Risk:
Emerging Genetics and Biological Mechanisms
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birth 6 years 14 years
Experience Refines Synaptic Circuits During Development Necessary for Precise Brain Wiring
Huttenlocher, 1979
Could Pruning Help Us Understand Age of Onset of Schizophrenia?
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Huttenlocher 1979
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Loss or less formed? Cause or Consequence? Mechanisms?
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Aswin Sekar MD/PhD student
Human Genetics Implicates Complement C4 In Schizophrenia
Steve McCarroll
School Broad Institute
Chromosome
Ass
oci
atio
n w
ith
sch
izo
ph
ren
ia
(-lo
g10
(p))
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Alleles of C4 shape schizophrenia risk in proportion to their effect on C4A expression
Sekar et al Nature 2016
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Complement “Tags” Synapses For Elimination in the
Healthy Developing Brain
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Questions and Challenges:
How and When to Intervene? Need for New/Early Biomarkers (Imaging/PET, CSF, other)
How Does Environment Converge with Genetics to Increase Risk?
Why is the Adolescent Brain Vulnerable?
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Bialas & Stevens 2014
A Common Mechanism of Synapse Loss
and Cognitive Dysfunction ?
Alzheimer’s Disease ( Soyon Hong et al., Science 2016) Glaucoma (Howell et al JCI 2011; Stevens et al.,2007) FTD (Huang et al., Cell 2016) Huntington’s Disease ( unpublished)
Disease Developing Brain Mature Brain
New Therapies? New Biomarkers?