Transcript dopamine - Oglethorpe University

Chapter 16
Schizophrenia
http://www.npr.org/programs/atc/features/2002/aug/schizophrenia/
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 Schizophrenia
 A serious mental disorder
characterized by disordered
thoughts, delusions,
hallucinations, and mood
disturbance.
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Schizophrenia

Positive Symptoms
© Najlah Feanny/CORBIS
 Delusions
 Hallucinations
 Disorganized

behavior
Negative Symptoms
 Social
withdrawal
 Mood disturbance
 Reduced motivation
John Nash
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Schizophrenia May Have Several
Outcomes
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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.
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A Possible Genetic Marker
A majority of patients and
45% of their relatives show
abnormal intrusions of
saccades in smooth pursuit
tasks.
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Treatment of Schizophrenia
No effective treatments prior to about 1950
 Discovery of chlorpromazine (Thorazine)

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 Schizophrenia
Positive
symptoms
Dopamine
hypothesis:
 Overactivity
of dopamine in
mesolimbic pathway (VTA to nucleus
accumbens and amygdala)
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
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
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Hypothesis
cont.:
 Disordered
thinking?
 System
so active that it does not discriminate
between thoughts, making it hard to follow a
logical sequence
 Terrifying
 Strong
element of delusions?
dopaminergic projection to amygdala
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Dopamine Hypothesis
Evidence for excessive dopamine
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Dopamine and Schizophrenia



Dopamine agonists
(cocaine,
amphetamine)
produce symptoms of
psychosis.
Dopamine antagonists
reduce psychotic
behavior.
Patients may have
abnormalities involving
dopamine
autoreceptors.
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 Schizophrenia
Positive
Symptoms
Chlorpromazine:
A
“typical neuroleptic”
 A dopamine receptor blocker for D2 receptors
Clozapine:
 An
“atypical neuroleptic”
 An antipsychotic drug that blocks D4 receptors
in the nucleus accumbens
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Long-term Use of Typical Neuroleptics
Often Produce Serious Side Effects
Tardive dyskinesia involves tremors and involuntary
movements.

Supersensitivity: increased sensitivity of neurotransmitter
receptors (D2) 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

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Dopamine Hypothesis
Evidence for increase in D3 receptors
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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.
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 Schizophrenia
Negative
Brain
symptoms
damage:
 Many
of the negative symptoms are
also seen in people with brain
damage
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Search for Brain Abnormalities
Evidence for changes in ventricular size
Courtesy D.R. Weinberger, NIMH, St. Elizabeth’s
Hospital, Washington, D.C.
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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

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Search for Brain Abnormalities
Loss of gray matter with age
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Search for Brain Abnormalities
Loss of gray matter with age
Cause of
delay of
onset??
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The Hypofrontality Hypothesis
Courtesy Dr. Karen F. Berman, Clinical Brain Disorders Branch,
NIMH, NIH


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.
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How are positive & negative
symptoms related?
Dopamine
Hypoactivity
(too little DA)
Dopamine hyperactivity
(too much DA)
Prefrontal
Cortex
GABA neurons
NA
VTA
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Possible Causes of Brain Abnormalities
Seasonal Effect
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Possible Causes of Brain Abnormalities
Seasonal Effect – Flu in 2nd trimester
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Possible Causes of the Brain
Abnormalities
Latitude
effect:
 The
increased incidence of schizophrenia in
people born far from the equator.
Nutritional
 Hunger
deficiency
Winter study
 Thiamine
deficiency
 Vitamin D deficiency (latitude effect?)
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Possible Causes of the Brain
Abnormalities

Father’s Age
20s  1:121 people schizophrenic
 50s  1:47 people schizophrenic
 Late
 Why?
 Maybe
problem with spermatocytes
Produce sperm
 Must replicate every 16 days
 Possible copying errors

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Possible Causes of the Brain
Abnormalities
Rh
incompatibility
 Mother
Rh neg,
 1st baby Rh pos,
 2nd baby Rh pos (antibodies attack)
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 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.
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