Schizophrenia

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Schizophrenia

• Aberrant neurochemistry

• Definition and symptoms
• Genetic basis
• Abnormalities in brain structure
• Drug treatment
• Hypotheses about underlying neurochemical
  abnormalities

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Treatment of Schizophrenia
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Treatment of Schizophrenia
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Treatment of Schizophrenia
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Treatment of Schizophrenia
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Treatment of Schizophrenia
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Treatment of Schizophrenia
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Treatment of Schizophrenia
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Drug Treatments of Schizophrenia
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Drug Treatments of Schizophrenia
Chlorpromazine
Reserpine
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How do these drugs work?

• Precise actions were not known!
• Side effects provided clues
• -Tremors and jerkiness in patients movements
• Parkinsons disease
• -discovery of dopamine
• precursor, L-dopa

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If L-dopa ? dopamine and ? Parkinsonism
and chlorpromazine/reserpine ? Parkinsonism
Then chlorpromazine/reserpine ?
dopamine Schizophrenia due to excess activity
of dopamine
Dopamine hypothesis
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Dopamine Hypothesis

• hyperfunctioning of dopamine circuits
• -presynaptic effect
• excessive release of dopamine
• -postsynaptic effect
• excessive sensitivity of dopamine receptors
• excess of dopamine receptors

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How do these drugs work?
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How do these drugs work?

• Chlorpromazine and reserpine are dopamine
• antagonists

Chlorpromazine competitive antagonist
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Drug actions at the synapse

• antagonists prevent the action of NT

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How do these drugs work?

• Chlorpromazine and reserpine are dopamine
• antagonists

Reserpine not a dopamine blocker Depletes
stores less dopamine released with each action
potential
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Other evidence for Dopamine Hypothesis

• amphetamine psychosis
• binding affinity assays

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Some Problems with the Dopamine Hypothesis

• Not all patients respond to drug treatment
• Full spectrum of symptoms not resolved
• Drugs not specific
• Atypical antipsychotics

e.g. Clozapine -may increase dopamine release in
some brain regions! -blocks serotonin receptors
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Ongoing Issues for the Biological Basis of
Schizophrenia

• The disorder
• The cause
• The treatment
• Dopamine presynaptic versus postsynaptic
• Other neurotransmitters (serotonin, glutamate)

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• Brain - structure and function
• Disordered brain - Schizophrenia
• Brain Behavior (brain plasticity)

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Brain Plasticity changing your mind
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In the rest of todays class

• Brain plasticity is now an accepted feature of
  brain function
• How do experiences change the brain?
• Model of learning at the level of the cell
• Evidence that different experiences alter
  structure of brain and behavioral outcome

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How do experiences change the brain?
Donald Hebb (1949)
Learning via the strengthening of existing
synapses
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Hebbs model of how synapses are strengthened
Before learning
After learning
?
Electrical potential
Electrical potential

• Metabolic change
• Structural change

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A laboratory model of Hebbs synapse
Bliss Lømo, 1973
Long-term potentiation in the hippocampus
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A laboratory model of Hebbs synapse
Long-term potentiation in the hippocampus
record
stimulate
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Synaptic plasticity
Learning via the strengthening of existing
synapses Postulated Hebbian synapse
Before learning
After learning
Electrical potential
Electrical potential
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Synaptic plasticity
Learning via the strengthening of existing
synapses Postulated Hebbian synapse
Before learning
After learning
or
Electrical potential
Electrical potential
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Experiences modify synapses

• Hebbs theory about how learning changes
  synapses
• Bliss Lomos empirical model of how learning
  changes synapses

"To learn is to change. Education is a process
that changes the learner."                      
                                 George Leonard 
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In the rest of todays class

• Brain plasticity is now an accepted feature of
  brain function
• How do experiences change the brain?
• Model of learning at the level of the cell
• Evidence that different experiences alter
  structure of brain and behavioral outcome

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Enrichment Studies
Impoverished
Standard
Bennett, Diamond, Krech, Rosenzweig 1960s
Enriched
Looked at animals living under a variety of lab
conditions
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Measurable changes in brain as a function of
living environment

• Cortex size and weight
• Brain neurochemistry
• Cell body size

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Some resistance.
growth just of bigger and better synapses that
are already there, not growth of new connections
John Eccles, 1965
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Measurable changes in brain as a function of
living environment

• Cortex size and weight
• Brain neurochemistry
• Cell body size
• Structure of neurons
• More synapses

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Measurable changes in brain as a function of
living environment

• Cortex size and weight
• Brain neurochemistry
• Cell body size
• Structure of neurons
• More synapses
• More new neurons!

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More resistance
Read my lips NO NEW NEURONS!
Not a single cell with the physical
characteristics of a neuron born after infancy
was observed in the brain of any adult animal
Pasko Rakic The New Yorker 2001
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Adult brains make new neurons
Rat Hippocampus
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Measurable changes in brain as a function of
living environment

• Cortex size and weight
• Brain neurochemistry
• Cell body size
• Structure of neurons
• More synapses
• More new neurons

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Environmental enrichment enhances learning
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Experiences change brain and behavior
Experience
Brain
Behavior
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New behaviors modify future experiences
Experience
Brain
Behavior
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Experiences can also change how brain and
behavior interact
Experience
Brain
Behavior