1. 1 Chapter 16 Schizophrenia http://www.npr.org/programs/atc/features/2002/aug/schizophrenia/

2. 2 Schizophrenia  A serious mental disorder characterized by disordered thoughts, delusions, hallucinations, and mood disturbance.

3. 3 Schizophrenia Positive Symptoms  Delusions  Hallucinations  Disorganized behavior Negative Symptoms  Social withdrawal  Mood disturbance  Reduced motivation John Nash © Najlah Feanny/CORBIS

4. 4 Schizophrenia May Have Several Outcomes

5. 5 Genetics and Schizophrenia Concordance rate in identical twins is 50%. Adoption studies support a strong genetic role. As many as 70 genes may be involved.

6. 6 A Possible Genetic Marker A majority of patients and 45% of their relatives show abnormal intrusions of saccades in smooth pursuit tasks.

7. 7 Treatment of Schizophrenia No effective treatments prior to about 1950 Discovery of chlorpromazine (Thorazine)

8. 8 Schizophrenia  Positive symptoms  Dopamine hypothesis: Overactivity of dopamine in mesolimbic pathway (VTA to nucleus accumbens and amygdala)

9. 9 Schizophrenia  How are positive symptoms related to dopamine?  Hypothesis: Mesolimbic system important for reinforcement of behavior We all have irrational thoughts, but usually brush them aside But if mesolimbic system was active when the thought occurred, we might take it more seriously, leading to delusions Confirming piece of evidence: schizophrenics often report euphoria at onset of positive symptoms

10. 10  Hypothesis cont.: Disordered thinking?  System so active that it does not discriminate between thoughts, making it hard to follow a logical sequence Terrifying element of delusions?  Strong dopaminergic projection to amygdala

11. 11 Dopamine Hypothesis Evidence for excessive dopamine

12. 12 Dopamine and Schizophrenia Dopamine agonists (cocaine, amphetamine) produce symptoms of psychosis. Dopamine antagonists reduce psychotic behavior. Patients may have abnormalities involving dopamine autoreceptors.

13. 13 Schizophrenia  Positive Symptoms  Chlorpromazine: A “typical neuroleptic” A dopamine receptor blocker for D 2 receptors  Clozapine: An “atypical neuroleptic” An antipsychotic drug that blocks D 4 receptors in the nucleus accumbens

14. 14 Long-term Use of Typical Neuroleptics Often Produce Serious Side Effects Tardive dyskinesia involves tremors and involuntary movements. Supersensitivity: increased sensitivity of neurotransmitter receptors (D 2 ) to dopamine Due to side effects, about 50% now use atypical neuroleptics like clozapine. Courtesy David Healy, Academy for the Study of the Psychoanalytic Arts

15. 15 Dopamine Hypothesis Evidence for increase in D 3 receptors

16. 16 Problems With a Excessive Dopamine Hypothesis 25% of patients do not respond to dopamine antagonists. Atypical antipsychotic medications (clozapine) act primarily on neurotransmitters other than dopamine. Drugs change dopamine activity immediately, but patient may not improve for weeks. PCP produces symptoms similar to schizophrenia by blocking the NMDA glutamate receptor.

17. 17 Schizophrenia  Negative symptoms  Brain damage: Many of the negative symptoms are also seen in people with brain damage

18. 18 Search for Brain Abnormalities Evidence for changes in ventricular size Courtesy D.R. Weinberger, NIMH, St. Elizabeth’s Hospital, Washington, D.C.

19. 19 Schizophrenia and the Hippocampus Cell bodies in a control participant are arranged neatly. Cell bodies in a participant diagnosed with schizophrenia appear relatively disorganized. Courtesy Arnold B. Scheibel, University of California, Los Angeles

20. 20 Search for Brain Abnormalities Loss of gray matter with age

21. 21 Search for Brain Abnormalities Loss of gray matter with age Cause of delay of onset??

22. 22 The Hypofrontality Hypothesis Lower frontal lobe activity may account for the negative symptoms of schizophrenia. During rest (top) and an effortful cognitive test (bottom), patients with schizophrenia show less frontal lobe activity. Courtesy Dr. Karen F. Berman, Clinical Brain Disorders Branch, NIMH, NIH

23. 23 How are positive & negative symptoms related? VTA Prefrontal Cortex NA Dopamine Hypoactivity (too little DA) GABA neurons Dopamine hyperactivity (too much DA)

24. 24 Possible Causes of Brain Abnormalities Seasonal Effect

25. 25 Possible Causes of Brain Abnormalities Seasonal Effect – Flu in 2 nd trimester

26. 26 Possible Causes of the Brain Abnormalities  Latitude effect: The increased incidence of schizophrenia in people born far from the equator.  Nutritional deficiency Hunger Winter study  Thiamine deficiency  Vitamin D deficiency (latitude effect?)

27. 27 Possible Causes of the Brain Abnormalities Father’s Age  Late 20s  1:121 people schizophrenic  50s  1:47 people schizophrenic  Why?  Maybe problem with spermatocytes Produce sperm Must replicate every 16 days Possible copying errors

28. 28 Possible Causes of the Brain Abnormalities  Rh incompatibility Mother Rh neg, 1 st baby Rh pos, 2 nd baby Rh pos (antibodies attack)

29. 29 Schizophrenia  Early warning signs for children with abnormal prenatal development]\: Children who developed schizophrenia displayed more negative affect in their facial expression and were more likely to show abnormal movements. Children who developed schizophrenia also displayed poor social adjustment and did more poorly in school than their peers.