Genomic Imaging of Personality:

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Genomic Imaging of Personality Towards a
Molecular Neurobiology of Neuroticism Turhan
Canli, Ph.D. Graduate Program in Genetics,
and Dept. of Psychology Stony Brook University
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Neuroticism as a Fundamental DimensionOf Human
Personality
Low-N
High-N
calm relaxed secure self-satisfied unemotional
worried nervous insecure inadequate emotional

• Report more negative experiences
• Susceptible to negative mood induction
• Vulnerability for Depression, Anxiety, other
  Mood Disorders

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Phineas P. Gage
Source Dr. Hannah Damasio
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Heredity of Personality
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Old and New Concept of Behavioral Genetics
Hamer 2002
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Personality and the Brain
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Deconstructing Neuroticism
Psychological Domains
Attention
Perception
Feeling
Memory
Behavior
Systems
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Deconstructing Neuroticism
Psychological Domains
Attention
Perception
Feeling
Memory
Behavior
Systems
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Design
Press the button corresponding to the color as
quickly and accurately as you can
6 x
10 Neg
10 Pos
10 Neut
10 Pos
Laughter Happy Kitten
Murder Despair Hopeless
House Car Book
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Neuroticism AC Activation to Negative Words
Negative-Neutral
Canli et al., 2004, Beh. Neuroscience
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Deconstructing Neuroticism
Psychological Domains
Attention
Perception
Feeling
Memory
Behavior
Systems
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Design
Press left button for male face, right button
for female face as quickly and accurately as you
can
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Neuroticism De-Activation in SMG to Fearful Faces
Fear-Neutral
Supramarginal Gyrus
Neuroticism Score
Z 28 mm
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Deconstructing Neuroticism
Psychological Domains
Attention
Perception
Feeling
Memory
Behavior
Systems
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Design
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Neuroticism Middle Temporal Reactivity to
Negative Pictures
Negative-Neutral
Neuroticism Score
Canli et al., 2001, Beh. Neuroscience
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Whats next?

• Data show association between N and individual
  differences in brain activation to negative
  affective stimuli
• What is the mechanism?
• A genomic approach gets at the underlying
  molecular architecture

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From Behavioral to Molecular Genetics
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Heredity of Personality
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Genes are organized in Chromosome Pairs(one from
each parent)
www.sparkingreaction.info/ media/chromosomes.jpg
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Chromosomes are made of DNA Strands
www.alumni.ca/laued3e/ chromosome.jpg
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These DNA Strands can vary across Individuals
www.alumni.ca/laued3e/ chromosome.jpg
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A Single Nucleotipde Polymorphism (SNP)
www.alumni.ca/laued3e/ chromosome.jpg
G - Guanine
C - Cytosine
C - Cytosine
G - Guanine
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Lesch 1996 Neuroticism and Variants of the
Serotonin Transporter
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Deconstructing Neuroticism
Psychological Domains
Attention
Perception
Feeling
Memory
Behavior
Systems
Cells, Genes Molecules
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Genomic Imaging 5-HTT
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Serotonergic Neuron
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Hariri et al., Science, 20025-HTT s allele
increased amygdala activation to angry/fearful
faces
Task Face-matching vs. visuospatial matching
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Design
Press the button corresponding to the color as
quickly and accurately as you can (no resp. to
fix)
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Methods

• Subjects
• 41 healthy volunteers
• 5-HTT genotypes S-group12 (4M) ss and 16 (9 M)
  sl L-group 13 (6 M) ll
• No sig group diff in age, mood, neuroticism (or
  RTs), freq. of sex or ethnicity

• Scanning Parameters
• 3T Siemens Trio Scanner
• TR 1500 ms, TE 30 ms,
• Flip 80 degrees, FOV 22 x 22 cm
• 24 oblique (AC-PC) slices 5 mm thick
• 0 mm inter-slice space
• In-plane resolution
• 3.43 mm x 3.43 mm
• SPM2 2-sample ttest
• A priori region p lt .05, corrected, 10 voxels
  extent

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5-HTT affects amygdala activation to negative
stimuli
Negative Neutral
Canli et al., PNAS, 2005
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A new interpretation
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Beyond Affect and Amygdala
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Epigenesis in the Brain
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Gene x Life Stress Depression?

• Caspi et al., 2003, Science

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Design
Press left button for male face, right button
for female face as quickly and accurately as you
can
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Methods
Subjects 42 healthy, normal volunteers, 21 male,
genotyped for 5-HTT polymorphism 10 l/l versus
32 s/l or s/s Stimuli fixation, emotional and
neutral faces Measures mood, personality, life
stress

• 3T Scanner
• TR 3000 ms, TE 45 ms,
• Flip 80 degrees, FOV 20 x 20 cm
• 35 oblique slices 3.5 mm thick
• 0 mm inter-slice space
• In-plane resolution
• 2.35 mm x 2.35 mm
• SPM2 2-sample ttest
• A priori region p lt .05, corrected

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Gene x Life Stress in the Amygdala
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Caveats and Limitations

• Sample Size
• False Positives
• Polymorphisms N
• Still correlational!
• True causal models will require methods that
  manipulate genome

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Future Projects

• Other gene polymorphisms
• Gene-environment interactions
• Gene-sex interactions
• Gene-gene interactions
• True causal models will require methods that
  manipulate genome, i.e., transgenic animals

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Collaborators
Wuerzburg Klaus-Peter Lesch Andreas
Fallgatter Nicole Steigerwald
Yale Todd Constable Jamie Ferrie
Stony Brook GCRC Directors and Staff Nancy
Wyllie, Marie Gelato, Diane Ruenes, Tracey
Dourdounas, Joyce Quick, Ruthann Callahan,
Stephanie Musso, et al. Canli Lab Zenab
Amin Eliza Congdon Brian Haas Kazufumi Omura
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fMRI Setup
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The real Brain Anatomy
The Real Thing
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The imaged Brain Anatomy
An MRI image
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BOLD Response
Increased MRI signal
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Activation Statistics
Functional images
Time