Post on 03-Nov-2014
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Schizophrenia
Brian J. Piper, Ph.D.
Goals Symptoms of Schizophrenia
Causes
Antipsychotics Typical
Atypical
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. Cognition2. Behavior 3. Emotions
NOT Multiple PersonalityDisorder
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
Other forms of delusions include, delusions of persecution (“someone is following me”) or grandeur (“I am a
king”).
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)
This monologue illustrates fragmented, bizarre thinking with distorted beliefs called delusions (“I’m Mary Poppins”).
Example Patient
Gerald (upto 2:30): http://www.youtube.com/watch?v=gGnl8dqEoPQ
Haldol: classic antipsychotic drug
Delusions of grandeur: inappropriate beliefs about one’s self-worth or specialpowers
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
DSM5 Diagnosis of Schizophrenia
• Two or more of the following, including 1, 2, or 31. 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
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
Epidemiology of Schizophrenia
Frequency: 0.7%Sex: Males > Females in # and severityLow SES (downward drift)/African-AmericansRule of thirds
Sources: Anna K. Kring
Vincent van Gogh1853-1890
Brian Wilson1942-
John Nash1928-
Jack Kerouac1922-1969
Mary Todd Lincoln1818-1882
Schizophrenia
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
Typical?
The relationship between schizophrenia and aggression is controversial.
Renfrew (1996). Aggression & Its Causes.
The relationship between schizophrenia and aggression is controversial.
Disorganized: Increased risk of victimizationParanoid: small increase
Renfrew (1996). Aggression & Its Causes.
John W. Hinckley, Jr.Jared Lee Loughner
Accuracy of Diagnosis
SCZ- SCZ+
SCZ- Correct Diagnosis
Type Ierror
SCZ+ Type IIerror
CorrectDiagnosis
• 8 healthy pseduo-patients presented to 12 psychiatric hospitals with complaint of hearing voices
• Acted normal but 11 diagnosed as schizophrenic
• Fellow patients, but not staff, were suspicious
• Released after 7-52 days (mean = 19)
Decision
Rea
lity
Rosenhan (1973). Science, 179, 250-258.
0:37-3:30: http://www.youtube.com/watch?v=Kq-7uvVOoyk
1929-2012
Causes
• Demonic possession• “Refrigerator mothers”• Neurodevelopmental Disorder• Biochemical Imbalance
Abnormal Brain MorphologySome schizophrenia patients exhibit
morphological changes in the brain like enlargement of fluid-filled ventricles.
Both Photos: C
ourtesy of Daniel R
. Weinberger, M
.D., N
IH-N
IMH
/ NSC
Meta-Analysis
• 58 studies
• 1,588 SCZ patients
Region (Left or Right) % of Control
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.
Genetic Factors
Genetic Factors
The following shows the prevalence of schizophrenia in identical twins as seen
in different countries.
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 sonsHester: showed signs at age 11, institutionalized
Genetics: identicalEnvironment: identical (schizophrenic mom)Prenatal: ?
Wisconsin Card Sorting Test
• Developed by Esta Berg in 1950s
• Measures cognitive flexibility and perseverative behaviors (number, color, shape)
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.
Individual Differences in SCZ
Hypofrontality During WCST
Hypofrontality During Continuous Performance Test
• fMRI was completed during a Continuous Performance test
Volz et al. (1999). European Psychiatry, 14, 17-24.
Hypofrontality During Continuous Performance Test
• fMRI was completed during a Continuous Performance test
Volz et al. (1999). European Psychiatry, 14, 17-24.
Neurochemical ImbalanceTypical
Origin 1952
Example ChlorpromazineHaloperidol
Mechanism D2 antagonist
Treats + symptoms
Side-Effects Tardive dyskinesia
TD (20 sec): http://www.youtube.com/watch?v=fLwZQBJs8fI
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.
ComparisonTypical Atypical
Origin 1950s 1970
Example ChlorpromazineHaloperidol
Clozapine
Mechanism D2 antagonist D2 & 5-HT2A antagonist
Treats + symptoms + symptoms
Side-Effects Tardive dyskinesia Weight gain
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.
**
Beyond D2
• the dopaminergic (or serotonergic) model of schizophrenia may be too simplistic
Kerwin et al. (1999). Neuroscience, 39, 25-32.
Schizophrenia in Children
• More frequently recognized
9 min: http://www.youtube.com/watch?v=B9v4FsKXmj8
8 min: http://www.youtube.com/watch?v=UTUMt05_nCI
Self-Medication?
• Marijuana• Nicotine
Reduced Lifespan (N = 5,036,662)!
Male Life Expectancy
MaleYears Lost
FemaleLifeExpectancy
FemaleYears Lost
All (Psychiatric History - )
76.5 NA 80.9 NA
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.
Reduced Lifespan (N = 5,036,662)!
Male Life Expectancy
MaleYears Lost
FemaleLifeExpectancy
FemaleYears Lost
All (Psychiatric History - )
76.5 NA 80.9 NA
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.
Contributing Factorssuicide, accident, homicides, self-care, metabolic (?)
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– Schizophrenia– Order
Louis Wain (1860-1939)
Summary
• Symptoms ( + and - )• Current Biological Components (Not Diagnostic)
– Genetics– Brain Structure– Dopamine Receptors
VideocastOverman, 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?