Schizophrenia and Social Schizophrenia and Social CuesCuesDave Arendt

The RundownThe Rundown1% chance you’ll get it

◦ 50% of homeless◦ 3 million Americans get it

1.5 million suicidal 225,000 complete

Acquire during late teen years to middle adulthood◦ Ladies have a later onset

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

Symptom TypesSymptom Types

Positive Negative

Delusions◦ Paranoia◦ Grandiosity◦ Persecution◦ Thought broadcasting/insert

Hallucination◦ Olfactory◦ Visual◦ Auditory◦ Tactile

Thought disturbance◦ Not making sense◦ Painful detail◦ No goal in conversation◦ Inability to form thought

Flattened AffectDisorganized SpeechAhedoniaAttention deficitsEmotional Withdrawal

Dopamine - Dopamine - Too much of a Too much of a good thing?good thing?

Physiological Condition

Symptom Pharmacological Symptom

Increased DA Levels

Positive Symptoms

D1 Antagonist

Decreased DA Levels

Negative Symptoms

D2 Agonist

D2 receptor antagonist = first generation antipsychotic

Animal ModelAnimal ModelSystemic injection of NMDA antagonist

◦PCP, Ketamine◦Temporary Schizophrenic effect◦Positive symptoms stopped by DA

antagonistNRG1 – mutant mice

◦Tracked to familial Schizophrenia◦Gene associated with NMDA receptor

localization◦Physical symptoms similar to NMDA

antagonist modelsDA knockout mice

Glu

DAGABA

DA

Schizophrenia

Normal DA release

Less DANegativ

eSympto

m

More DAPositiveSympto

m

Current StudyCurrent Study

Do schizophrenics and controls differ in their social decision making?

SubjectsSubjects12 Schizophrenics

◦All outpatient◦All medicated◦Rated on PANSS assessment

21 Healthy Controls◦Certified non-crazy by means of MINI

test

An fMRI?An fMRI?

Scanning fMRI taskScanning fMRI taskRated a series of faces in

“either/or” fashion◦Trustworthy or Untrustworthy◦Older or Younger than 30yrs

Do You Look Trustworthy Do You Look Trustworthy ??

Trustworthy Features Non-Trustworthy Features

High inner eyebrowsPronounced

cheekbonesWide chinsShallow nose sellion

Low inner eyebrowsShallow cheekbonesThin chinsDeep nose sellion.

Winston et al (2002)

Rest 45sTask block 45s

16 total blocks = 25min total test time

Instructional

3s

Stimuli 1

s

Fixation cross

2s Fixation cross 45

s

“Age” or “Trustworthiness”

fMRI taskfMRI task

orNull Test

(15 sets)

“age”

After the fMRI scanning After the fMRI scanning tasktaskRe-rated all the faces for

trustworthiness◦Scale of 1 to 7 instead of either/or

Rank faces 1 to 7Rank faces 1 to 7No

differences among ranks

Distribution difference

No differences in scannerNo differences in scanner

Whole-Whole-Brain Brain ActivationActivation

Identified Regions of Identified Regions of InterestInterestAmygdalaPrefrontal cortexInsulaAnterior CingulateOccipital CortexRight Superior Temporal Sulcus

Overa

ll A

ctiv

ity

Act

ivit

y in t

rust

wort

hy

face

No significant posthoc results

Left medial OFC

DiscussionDiscussionWhole brain analysis identified

expected areas of activityDecreased amygdala activation

◦Memory retrieval of emotion◦Related study shows similar result in

emotional stimuli experiment

DiscussionDiscussionRight Insula activity

◦ Similar results in a nonemotional task◦ Interesting artifact of the experiment

Area associated with judgement and risk takingLeft medial OFC

◦ Part of PFC◦ Lesion or injury aligns behavior with

schizophrenics◦ May be effect rather than cause

Signs the Schizophrenic patients may be guessing rather than calculating a response◦ Random scoring pattern◦ Right insula