1. Schizophrenia and Social Cues Dave Arendt

2. The Rundown 1% 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

3. Symptom Types PositiveNegative 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 Affect Disorganized Speech Ahedonia Attention deficits Emotional Withdrawal

4. Dopamine - Too much of a good thing? Physiological Condition SymptomPharmacological Symptom Increased DA Levels Positive Symptoms D1 Antagonist Decreased DA Levels Negative Symptoms D2 Agonist D2 receptor antagonist = first generation antipsychotic

5. Animal Model Systemic injection of NMDA antagonist ◦ PCP, Ketamine ◦ Temporary Schizophrenic effect ◦ Positive symptoms stopped by DA antagonist NRG1 – mutant mice ◦ Tracked to familial Schizophrenia ◦ Gene associated with NMDA receptor localization ◦ Physical symptoms similar to NMDA antagonist models DA knockout mice

6. Glu DA GABA DA Schizophrenia Normal DA releaseLess DA Negative Symptom More DA Positive Symptom

7. Current Study Do schizophrenics and controls differ in their social decision making?

8. Subjects 12 Schizophrenics ◦ All outpatient ◦ All medicated ◦ Rated on PANSS assessment 21 Healthy Controls ◦ Certified non-crazy by means of MINI test

9. An fMRI?

10. Scanning fMRI task Rated a series of faces in “either/or” fashion ◦ Trustworthy or Untrustworthy ◦ Older or Younger than 30yrs

11. Do You Look Trustworthy ? Trustworthy FeaturesNon-Trustworthy Features High inner eyebrows Pronounced cheekbones Wide chins Shallow nose sellion Low inner eyebrows Shallow cheekbones Thin chins Deep nose sellion. Winston et al (2002)

13. Rest 45sTask block 45s 16 total blocks = 25min total test time Instructional 3s Stimuli 1s Fixation cross 2s Fixation cross 45 s “Age” or “Trustworthiness” fMRI task or Null Test (15 sets)

14. “age”

15. After the fMRI scanning task Re-rated all the faces for trustworthiness ◦ Scale of 1 to 7 instead of either/or

16. Rank faces 1 to 7 No differences among ranks Distribution difference

17. No differences in scanner

18. Whole-Brain Activation

19. Identified Regions of Interest Amygdala Prefrontal cortex Insula Anterior Cingulate Occipital Cortex Right Superior Temporal Sulcus

20. Overall Activity Activity in trustworthy face

21. No significant posthoc results

22. Left medial OFC

23. Discussion Whole brain analysis identified expected areas of activity Decreased amygdala activation ◦ Memory retrieval of emotion ◦ Related study shows similar result in emotional stimuli experiment

24. Discussion Right Insula activity ◦ Similar results in a nonemotional task ◦ Interesting artifact of the experiment  Area associated with judgement and risk taking Left 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