Schizophrenia

Brian J. Piper, Ph.D.

Goals Symptoms of Schizophrenia

Causes

Treatments

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

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

Epidemiology of Schizophrenia

Frequency: 0.7%Onset: 18-20sSex: Males > Females in # and severityLow SES/African-AmericansRule of thirds

Sources: Anna K. Kring, Brad Olson, & Peter Gray

Vincent van Gogh1853-1890

Brian Wilson1942-

John Nash1928-

Jack Kerouac1922-1969

Mary Todd Lincoln1818-1882

Schizophrenia & Artists?

DSM-IV Criteria for Diagnosis

• Impaired social/occupational/self-care

• 2 or more of the following:– Delusions: delusions of grandeur or

persecution– Hallucinations– Disorganized speech– Disorganized behavior: mannerisms– Negative symptoms

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

Typical?

The relationship between schizophrenia and aggression is controversial.

Renfrew (1996). Aggression & Its Causes.

Typical?

The relationship between schizophrenia and aggression is controversial.

Disorganized: Increased risk of victimizationParanoid: small increase

Renfrew (1996). Aggression & Its Causes.

John Hinckley, Jr.

Jared Lee Loughner

Causes

• Demonic possession– Blood loss– Damage to brain

• “Refrigerator mothers”

• Neurodevelopmental Disorder

Abnormal Brain MorphologySchizophrenia patients may 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

The likelihood of an individual suffering from schizophrenia is 50% if their identical

twin has the disease (Gottesman, 2001).

0 10 20 30 40 50Identical

Both parents

Fraternal

One parent

Sibling

Nephew or niece

Unrelated

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: ?

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.

Viral Infection

Schizophrenia has also been observed in individuals who contracted a viral

infection (flu) during the middle of their fetal development.

Natural Logarithm of Relative Risks (and 95% Confidence Intervals) for Subjects Included in Eight Ecological Studies from Europe, America, and Australia (Type A Studies) of Risk for

Schizophrenia Associated with Exposure to 1957 Influenza Pandemic During Second Trimester of Prenatal Life.

Selten J et al. Schizophr Bull 2009;36:219-228http://en.wikipedia.org/wiki/Natural_logarithm

Individual Differences in SCZ

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.

Neurochemical ImbalanceTypical Atypical

Origin 1950s 1970

Example ChlorpromazineHaloperidol

Clozapine

Mechanism D2 antagonist D2 & 5-HT2A antagonist

Treats + symptoms + symptoms

Side-Effects Tardive dyskinesia Weight gain

TD (20 sec): http://www.youtube.com/watch?v=fLwZQBJs8fI

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). Neuropsychobiol 32, 1216-1223.

**

Self-Medication?

• Marijuana• Nicotine

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

– Genetics– Brain Structure– Dopamine Receptors