Lecture 22 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University. Focus is on typical and atypical antipsychotics.

1. Schizophrenia
Brian J. Piper, Ph.D.

2. Goals
 Symptoms of Schizophrenia
 Causes
 Antipsychotics
 Typical
 Atypical

3. Schizophrenia
The Greek translation is schizein “split” and
phren “mind” which refers to a split from
reality. A group of severe disorders
characterized by atypical:
1. Cognition
2. Behavior NOT Multiple Personality
Disorder
3. Emotions

4. Symptoms of Schizophrenia
Positive symptoms: the presence of inappropriate
behaviors
delusions
hallucinations: auditory >>> visual > other
disorganized talking: “word salad”
movements
Negative symptoms: the absence of appropriate
behaviors
flat affect: joy, anger, disgust
anhedonia
catatonia: waxy flexibility

5. Disorganized & Delusional Thinking
This morning when I was at Hillside [Hospital], I was
making a movie. I was surrounded by movie stars …
I’m Mary Poppins. Is this room painted blue to get me
upset? My grandmother died four weeks after my
eighteenth birthday.”
(Sheehan, 1982)
Other forms of delusions include, delusions of
This monologue illustrates fragmented, bizarre
thinking with (“someone is following delusions
persecution distorted beliefs called me”) or
grandeur (“I am a king”).
(“I’m Mary Poppins”).

6. Example Patient
Haldol: classic antipsychotic drug
Delusions of grandeur: inappropriate beliefs about one’s self-worth or special
powers
Gerald (upto 2:30): http://www.youtube.com/watch?v=gGnl8dqEoPQ

7. Auditory Hallucinations
For almost 7 years, except during sleep, I continue to hear voices. They accompany me
to every place and at all times, when I’m in conservations with other people, they persist,
undeterred, even when I concentrate on other things, for instance, read a book, play the
piano, etc. Only when I’m talking aloud to other people or to myself are they drowned by
the stronger sound of the spoken word and therefore inaudible to me.
Recounted by Ann M. Kring, Ph.D.
Pros & Cons
Behavioral strategies (& family discord)
Command Hallucinations

8. DSM5 Diagnosis of
Schizophrenia
• Two or more of the following, including 1,
2, or 3
1. Delusions
2. Hallucinations
3. Disorganized speech
4. Grossly abnormal psychomotor behavior
5. Negative symptoms
• Duration: 1 month during last 6
• Social/occupational dysfunction
• Exclusion: medical condition or drug

9. Animal Models of Schizophrenia
• Amphetamine: hyperactivity & stereotypy
• Apomorphine: D1-5 agonist, causes
hyperactivity & stereotypy (sniffing, grooming, head-bobbing, nail biting, and circling)
• Phecyclidine (PCP): dopamine release &
NMDA antagonist
• Prepulse Inhibition: classical conditioning

10. Epidemiology of
Schizophrenia
Frequency: 0.7%
Sex: Males > Females in # and severity
Low SES (downward drift)/African-Americans
Rule of thirds
Sources: Anna K. Kring

12. Vincent van Gogh
1853-1890
Mary Todd Lincoln
1818-1882
Brian Wilson
1942-
Schizophrenia
Jack Kerouac
John Nash
1922-1969
1928-

13. Subtypes (DSM-IV-TR only)
• Catatonic: immobility
• Disorganized: disorganized speech or
behavior, affective flattening
• Paranoid:
– Present: delusions & auditory hallucinations,
possible religiosity
– Absent: disorganized behavior & affective
flattening
Illusory Correlation

14. Typical?
The relationship between schizophrenia and aggression is
controversial.
Renfrew (1996). Aggression & Its Causes.

15. John W. Hinckley, Jr.
Jared Lee Loughner
The relationship between schizophrenia and aggression is
controversial.
Disorganized: Increased risk of victimization
Paranoid: small increase
Renfrew (1996). Aggression & Its Causes.

16. Accuracy of Diagnosis
Decision • 8 healthy pseduo-patients
SCZ- SCZ+ presented to 12 psychiatric
SCZ- Correct Type I hospitals with complaint of hearing
Reality
Diagnosis error voices
• Acted normal but 11 diagnosed as
SCZ+ Type II Correct
schizophrenic
error Diagnosis
• Fellow patients, but not staff, were
suspicious
• Released after 7-52 days (mean =
19)
1929-2012
0:37-3:30: http://www.youtube.com/watch?v=Kq-7uvVOoyk
Rosenhan (1973). Science, 179, 250-258.

17. Causes
• Demonic possession
• “Refrigerator mothers”
• Neurodevelopmental Disorder
• Biochemical Imbalance

18. Abnormal Brain Morphology
Some schizophrenia patients exhibit
morphological changes in the brain like
enlargement of fluid-filled ventricles.
Both Photos: Courtesy of Daniel R. Weinberger, M.D., NIH-NIMH/ NSC

19. Meta-Analysis
• 58 studies Region (Left or Right) % of
Control
• 1,588 SCZ patients L Lateral Ventricle 130
R Lateral Ventricle 120
Gray Matter 96
White Matter 98
L Frontal Lobe 95
L Hippocampus 95
L Amygdala 91
L Thalamus 96
R Thalamus 96
Wright et al. (2000). Am J Psychiatry, 157, 16-25.

20. Genetic Factors

21. Genetic Factors
The following shows the prevalence of
schizophrenia in identical twins as seen in
different countries.

22. Genain Sisters
“Genain”: Greek “dire birth”, born 1930, all
hospitalized for schizophrenia by early 20s,
probability = 1.5 billion
Nora: intermediate (jobs, no family)
Iris: intermediate (jobs, no family)
Myra: secretary, married, 2 sons
Hester: showed signs at age 11, institutionalized
Genetics: identical
Environment: identical (schizophrenic mom)
Prenatal: ?

23. Wisconsin Card Sorting Test
• Developed by Esta Berg in
1950s
• Measures cognitive
flexibility and
perseverative behaviors
(number, color, shape)

24. Neuropsych Testing of Genain
Sisters at age 68
• Digit Span: working
memory
• Trail Making Test: set
shifting
• Continuous
Performance Test:
attention
Mirsky et al. (2000). Schizophrenia Bulletin, 26, 699-708.

25. Individual Differences in SCZ

26. Hypofrontality During WCST

27. Hypofrontality During
Continuous Performance Test
• fMRI was completed during a Continuous
Performance test
Volz et al. (1999). European Psychiatry, 14, 17-24.

28. Hypofrontality During
Continuous Performance Test
• fMRI was completed during a Continuous
Performance test
Volz et al. (1999). European Psychiatry, 14, 17-24.

29. Neurochemical Imbalance
Typical
Origin 1952
Example Chlorpromazine
Haloperidol
Mechanism D2 antagonist
Treats + symptoms
Side-Effects Tardive dyskinesia
TD (20 sec): http://www.youtube.com/watch?v=fLwZQBJs8fI

30. Drug Therapies
Psychopharmacology is the study of drug effects
on mind and behavior.
With the advent of drugs, hospitalization in mental
institutions has rapidly declined.

31. Comparison
Typical Atypical
Origin 1950s 1970
Example Chlorpromazine Clozapine
Haloperidol
Mechanism D2 antagonist D2 & 5-HT2A antagonist
Treats + symptoms + symptoms
Side-Effects Tardive dyskinesia Weight gain

32. Concern
• Adult monkeys
received typical *
(haloperidol) or *
atypical (olanzapine)
antipsychotics for 2
years at doses similar
to schizophrenics.
• Gray matter in
parietal cortex was
examined.
Konopaske et al. (2007). Neuropsychopharmacology, 32, 1216-1223.

33. Beyond D2
• the dopaminergic (or serotonergic) model
of schizophrenia may be too simplistic
Kerwin et al. (1999). Neuroscience, 39, 25-32.

34. Schizophrenia in Children
• More frequently recognized
8 min: http://www.youtube.com/watch?v=UTUMt05_nCI
9 min: http://www.youtube.com/watch?v=B9v4FsKXmj8

35. Self-Medication?
• Marijuana
• Nicotine

36. Reduced Lifespan
(N = 5,036,662)!
Male Male Female Female
Life Expectancy Years Life Years Lost
Lost Expectancy
All (Psychiatric 76.5 NA 80.9 NA
History - )
Schizophrenia 57.8 18.7 64.6 16.3
Bipolar 62.9 13.6 68.8 12.1
Laursen (2011). Schizophrenia Research, 131, 101-104 .

37. Reduced Lifespan
(N = 5,036,662)!
Male Male Female Female
Life Expectancy Years Life Years Lost
Lost Expectancy
All (Psychiatric 76.5 NA 80.9 NA
History - )
Schizophrenia 57.8 18.7 64.6 16.3
Bipolar 62.9 13.6 68.8 12.1
Contributing Factors
suicide, accident, homicides,
self-care, metabolic (?)
Laursen (2011). Schizophrenia Research, 131, 101-104 .

38. Art During Disease Progression
• A English artist, who was
fascinated by cats, painted
these pictures over a period of
time in which he became
mentally ill.
• Pro
– Paranoia
– Disorganization
• Con Louis Wain (1860-1939)
– Schizophrenia
– Order

39. Summary
• Symptoms ( + and - )
• Current Biological Components (Not Diagnostic)
– Genetics
– Brain Structure
– Dopamine Receptors

40. Videocast
Overman, Gerald (2010). Antipsychotic treatment & tolerability. Starts about 4:40 (ends abruptly):
http://videocast.nih.gov/Summary.asp?File=15991
What are the pros and cons of the typical and atypical
antipsychotics?
What is EPS? What areas of the brain are important for this?
If you had a family member that was recently diagnosed with
SCZ, what drug (or drug class) would you hope that the
psychiatrist would prescribe?