Transcript Dave Arendt - USD Biology

Schizophrenia and Social Cues
Dave Arendt
The Rundown
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1% chance you’ll get it
◦ 50% of homeless
◦ 3 million Americans get it
 1.5 million suicidal
 225,000 complete
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Acquire during late teen years to middle adulthood
◦ Ladies have a later onset
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Very heritable – twin studies at 73 to 90%
◦ Deletions and duplications genes associated with axonal
guidance and synaptogenesis
◦ Identical twins only 50% so its also environmental
Positive
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Delusions
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Paranoia
Grandiosity
Persecution
Thought broadcasting/insert
Hallucination
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Negative
Olfactory
Visual
Auditory
Tactile
Flattened Affect
 Disorganized Speech
 Ahedonia
 Attention deficits
 Emotional Withdrawal
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Thought disturbance
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Not making sense
Painful detail
No goal in conversation
Inability to form thought
Symptom Types
Dopamine - Too much of a good thing?
D2 receptor antagonist = first generation antipsychotic
Physiological
Condition
Symptom
Pharmacological
Symptom
Increased DA
Levels
Positive
Symptoms
D1 Antagonist
Decreased DA
Levels
Negative
Symptoms
D2 Agonist
Animal Model
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Systemic injection of NMDA antagonist
◦ PCP, Ketamine
◦ Temporary Schizophrenic effect
◦ Positive symptoms stopped by DA antagonist
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NRG1 – mutant mice
◦ Tracked to familial Schizophrenia
◦ Gene associated with NMDA receptor
localization
◦ Physical symptoms similar to NMDA antagonist
models
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DA knockout mice
Glu
Schizophrenia
DA
GABA
DA
Less
Normal
DA DAMore
release
DA
Negative
Positive
Symptom
Symptom
Current Study
Do schizophrenics and controls differ in
their social decision making?
Subjects
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12 Schizophrenics
◦ All outpatient
◦ All medicated
◦ Rated on PANSS assessment
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21 Healthy Controls
◦ Certified non-crazy by means of MINI test
An fMRI?
Scanning fMRI task
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Rated a series of faces in “either/or”
fashion
◦ Trustworthy or Untrustworthy
◦ Older or Younger than 30yrs
Do You Look Trustworthy ?
Trustworthy Features
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High inner eyebrows
Pronounced cheekbones
Wide chins
Shallow nose sellion
Non-Trustworthy Features
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Low inner eyebrows
Shallow cheekbones
Thin chins
Deep nose sellion.
Winston et al (2002)
fMRI task
16 total blocks = 25min
total test time
Task block 45s
“Age” or
“Trustworthiness”
(15 sets)
or
Null Test
Rest 45s
“age”
After the fMRI scanning task
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Re-rated all the faces for trustworthiness
◦ Scale of 1 to 7 instead of either/or
Rank faces 1 to 7
No differences
among ranks
 Distribution
difference
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No differences in scanner
Whole-Brain
Activation
Identified Regions of Interest
Amygdala
 Prefrontal cortex
 Insula
 Anterior Cingulate
 Occipital Cortex
 Right Superior Temporal Sulcus
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Activity in trustworthy face
Overall Activity
No significant posthoc results
Left medial OFC
Discussion
Whole brain analysis identified expected
areas of activity
 Decreased amygdala activation
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◦ Memory retrieval of emotion
◦ Related study shows similar result in
emotional stimuli experiment
Discussion
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Right Insula activity
◦ Similar results in a nonemotional task
◦ Interesting artifact of the experiment
 Area associated with judgement and risk taking
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Left medial OFC
◦ Part of PFC
◦ Lesion or injury aligns behavior with schizophrenics
◦ May be effect rather than cause
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Signs the Schizophrenic patients may be guessing
rather than calculating a response
◦ Random scoring pattern
◦ Right insula