Biomarkers in Mental Illness Studies

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Biomarkers in Mental Illness Studies

• Guido Gerig and Martin Styner
• gerig_at_cs.unc.edu
• Taylor Grandy Professor of Computer Science and
  Psychiatry
• University of North Carolina at Chapel Hill

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Genetics and Disease Susceptibility
Phenotype 1 Phenotype 2 Phenotype 3
Phenotype 4
Ethnicity Environment
Age Gender
Identify Genes
Pharmacokinetics
Metabolism
Endocrine
Biomarker Signatures
Physiology
Proteome
Transcriptome
Immune
Morphometrics
Predictive Disease Susceptibility
Source Terry Magnuson
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Data Heterogeneity and Complexity
Genomic, proteomic, transcriptomic, metabalomic,
protein-protein interactions, regulatory
bio-networks, alignments, disease, patterns and
motifs, protein structure, protein
classifications, specialist proteins (enzymes,
receptors),
Proteome
Source Carole Goble (Manchester)
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Clinical Study Ventricle Shape in Twin
Schizophrenia Study

• Twin Pairs
• Monozygotic (MZ) Identical twins
• Dizygotic (DZ) Nonidentical twins
• MZ-Discordant (MZ-DS) for Schizophrenia
  Identical twins affected at risk pairs
• Nonrelated (NR) age/gender matched
• Focus on ventricle size and shape
• Data D. Weinberger, NIMH

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Application Twin Study
Collection of ventricular shapes of 4 twin pairs
(unsorted)
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Twin Study ctd.
Collection of ventricular shapes of twin pairs
(4 out of 10 pairs)
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Visual Comparison Shape similarity
MZ
MZ Twin Pairs
DZ
DZ Twin Pairs
Size Normalization
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Clinical Study Statistical Analysis of
Structures

• Types of Analysis
• Pairwise co-twin similarity (are MZ pairs more
  similar than DZ)
• Group differences Healthy versus Disease
• Volume or Shape

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SPHARM Parametrization
Mono- zygotic twin pairs
T1AL / T1BL
T1BR / T1AR
T2AL / T2BL
T2BR / T2AR
Dizygotic twin pairs
T10AL / T10BL
T10BR / T10AR
T8AL / T8BL
T8BR / T8AR
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Global Shape Distance Metrics

• Pairwise MSD between surfaces
• PDM Signed or unsigned distance to template at
  corresponding points

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Volume Differences between co-twin Ventricle Pairs
Pairwise volume differences mostly
non-significant MZ DS DZltNR
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Shape Differences between co-twin Ventricle Pairs
Pairwise shape similarity MZ DS lt DZ lt
NR Pairwise similarity parallel to genetic
similarity
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Shape Differences between co-twin Ventricle Pairs
Pairwise shape similarity MZ DS lt DZ lt
NR Pairwise similarity parallel to genetic
similarity
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Group Tests

• Healthy ventricle template
• Both subgroups of the MZ discordant twins
  (affected and at risk) compared to healthy
• Questions
• Effect of schizophrenia on ventricles?
• At risk subject?

Healthy All
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Group Tests of Ventricular Volumes
All tests nonsignificant SZ do not show
ventricle volume difference
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Group Tests Shape Distance to Healthy
Co-twin at risk, healthy
Co-twin schizophr.
Healthy All

• Both subgroups of MZ discordant for SZ (affected
  and at risk) differ.
• Ventricular shape seems to be marker for disease/
  vulnerability (?)
• Shape is much better marker than volume

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UNC Centers to study Genetics and Brain
Morphology/Function in Mental Illness

• UNC STAART Center
• Studies to Advance Autism Research and Treatment
• UNC Autism Research
• Brain development in autistic children (1-6yrs)
• Investigate the genetic and neurobiological basis
  of autism
• UNC Neurodevelopmental Disorders Res. Core NDRC
• Resource for Neurodevelopmental Studies
• UNC Conte Center (Pathophysiology of
  Schizophrenia)
• Early Brain Development in High-Risk Children
• Prospective Study of the Onset of Schizophrenia
• Search for Neurostructural Phenotypes Understand
  origins, early diagnosis ? early intervention