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CHAPTER 14
Psychological
Disorders
Schizophrenia
Schizophrenia
• Schizophrenia is a disabling disorder characterized by
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perceptual disturbances
Emotional disturbances
intellectual deficits
loss of contact with reality
Often an inability to function in life.
• Incidence rate:
– estimated that 3 million Americans will develop schizophrenia during
their lifetime.
– Approximately 2% of population
– 100,000 patients take up 20% of psychiatric beds in the U.S.
– Many more receive outpatient care.
Diagnosing Schizophrenia
• Must exhibit some combination of several symptoms:
– Hallucinations :
• internally generated perceptual experiences
• E.g., voices telling the person what to do.
– Delusion :
• false, unfounded beliefs,
• such as that one is a messenger from God.
– Paranoia: characterized by delusions of persecution.
– Disordered thought:
• Lack of logic in thought processes
• Word salad or fleeting thoughts
– Inappropriate emotions or lack of emotion
– Social withdrawal.
Positive vs. negative
symptoms
• Positive symptoms: Characterized by the the presence or
exaggeration of behaviors
– Include
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delusions
hallucinations
thought disorder
bizarre behavior
• Negative symptoms: Characterized by the absence or
insufficiency of normal behaviors
– include
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lack of affect (emotion)
inability to experience pleasure
lack of motivation
poverty of speech
impaired attention.
etiology
• Schizophrenia is a familial disorder:
– Incidence of schizophrenia higher among the relatives of
schizophrenics than in general population.
– Identical twins of schizophrenics are three times as likely to be
schizophrenic as the fraternal twins of schizophrenics.
• The heritability for schizophrenia has been estimated at
between .60 and .90.
• This means that 10-40% of the variability is due to
environmental factors.
Causes of Schizophrenia
• Scientistss looking for a genetic cause:
– Suggest may be genetic due to relatively constant rate of disorder
– Prevalence quite steady world wide
• The genes primarily concerned with
– neuronal migration,
– neuroreceptor development or sensitivity
– neurotransmitter activity.
– teasing out the genes’ relationships to behavioral symptoms.
• Notice these genes involve developmental aspects of the
brain, suggesting schizophrenia is a developmental
disorder.
Causes of Schizophrenia
• Cannot rule out effects of the environment
• Recent studies suggest is an interaction between environment and
genetic predisposition
• Vulnerability model:
– Some threshold of causal forces exceeded = illness to occur.
– Environmental challenges combine with person’s genetic
vulnerability to exceed that threshold.
– Genes determine vulnerability, not actual disease
– Interaction of heredity and environment
History of treatment
• Early 20th century:
– Little could be done to treat psychotic patients until mid1950s
– In mid 1950’s: variety of antipsychotic medications arrived on
the scene.
– Most important was chlorpromazine
• Anitpsychotics not originally designed to treat schizophrenia
– Often is case in medicine
– Most often in mental health
– Too little understanding of disease to develop specific meds
– Tried horse tranquilizers, brain surgeries, other wild
treatments
History of treatment
• Chlorpromazine or Thorazine:
– Tried with wide variety of mental illnesses
– Used it because it calmed surgical patients (and horses)
– Found it reduced schizophrenia symptoms
• NOT clear why chlorpromazine worked,
• Traditional tranquilizers have little or no usefulness in
treating schizophrenia.
• Only Thorazine seemed to calm these patients
Amphetamine hypothesis
• Amphetamine
– Overdose causes psychotic behavior indistinguishable from
schizophrenia,
– Includes symptoms such as hallucinations and paranoid delusions.
– Researchers determined: Amphetamine produces these symptoms by
increasing dopaminergic activity
– Eventually led to the dopamine hypothesis
• Dopamine Hypothesis
– schizophrenia involves excessive dopamine activity in the brain.
– blockade of type D2 dopamine receptors is essential for a drug to have
an antipsychotic effect,
– effectiveness directly related to drug’s D2 receptor blocking potency.
Treatment Side Effects
• Unfortunately, severe side effects from treatment
• Tardive Dyskinesia
– Prolonged use of antidopamine drugs often produces
– Includes permanent tremors and involuntary movements caused by
blocking of dopamine receptors in the basal ganglia.
– Pill rolling, grimacing, etc.
• http://www.youtube.com/watch?v=BJjXqKa4cbE
• http://www.youtube.com/watch?v=HEKxWzvoD7M
• The effect appears to be due to a compensatory
increase in the sensitivity of D2 receptors in the basal
ganglia.
Newer drugs
• Atypical antipsychotics
– Risperidal; Olazapine, etc.
– Introduced in early 1990s
– Are referred to as atypical because work slightly differently than
original D2 antagonists.
• How are they different?
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Target more than just D2 receptors
Produce motor problems only at much higher doses
Later onset of motor problems
Major side effects, particularly on white blood cells.
Some suggest atypical antipsychotics are 15-25% more effective than
conventional antipsychotics; data NOT support this.
• Although target receptors other than the D2, those that lack at
least a modest effect at D2 receptors are therapeutically
ineffective.
Is it just the DA system?
• Phencyclidine (PCP):
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elicits some of the symptoms of schizophrenia
mimics schizophrenia better than amphetamine does.
PCP inhibits the NMDA glutamate receptor
Suggests that reduced glutamate might be a factor in schizophrenia.
• Glutamate theory:
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Reduced glutamate activity involved in schizophrenia
Strong theoretical and therapeutic promise with this theory.
The glutamate system influences number of dopamine receptors.
Atypical antipsychotics also affect the serotonin system, which helps
regulate the dopamine system.
Brain changes in
Schizophrenia
• Several changes in brain of individuals with Schizophrenia
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Reduced cortical gray matter
Reduced limbic area volume
Enlarged fissures and sulci
Enlarged ventricles in the brains of schizophrenics.
Deficits are often accompanied by enlarged ventricles.
• Ventricular enlargement serves as a marker or indicator of the
tissue deficiency
– Ventricles expand to take up space normally occupied by brain cells
– Suggests actual neuronal loss
– Degree of ventricular enlargement correlated with decrease in IQ.
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Brain changes in
Schizophrenia
• Are deficits due to loss of specific area or coordination of
several areas?
– Recent research: suggest schizophrenia due to disordered connections
between parts of the brain
– Not due to localized malfunction.
– This consistent with findings of reduced white matter in the brains of
schizophrenics.
– Remember: White matter= axons
• Reduction not due to loss of neurons themselves, but loss of
connections between neurons
– Do connections die, resulting in symptoms?
– Do symptoms produce loss of neurons?
Ventricle size in normals and schizophrenics
(a) Ventricle-to-brain ratios (VBR; ventricular area divided by brain area,
multiplied by 100) of normal controls and chronic schizophrenics. Dotted
horizontal lines indicate group means.
(b) Magnetic resonance imaging scans of identical twins, one normal and one
schizophrenic.
Changes in
cognitive function
• Many schizophrenics perform poorly
on the Wisconsin Card Sorting Task
• Wisconsin Card sorting Task
– Sort cards by color, shape, symbol
– Have subject switch to new type of sorting
across several trials
– Requires the individual to switch from one
card sorting strategy to another.
– Many schizophrenics perform poorly on
the test, persisting with the previous
sorting strategy.
Changes in
cognitive function
• Poor performance on Wisconsin Sorting Task suggests
poor prefrontal activity
– Normal individuals: increased activation in the prefrontal area
during the test
– Schizophrenics do not.
• This hypofrontality appears to involves DA deficiency
– Administering amphetamine to schizophrenics increases
blood flow in the prefrontal cortex
– Amphetamine also improves performance on the Wisconsin
Card Sorting Task.
– Question is why DA decreases!
Blood flow in normal and schizophrenic brains during card sorting test
(a) The upper images are of the left and right hemispheres of a normal
brain; the schizophrenic brain is below. Red and yellow represent greatest
activation.
(b) Note Activity in the dorsolateral prefrontal cortex, whose location is
identified figure to right, appears most compromised.
Why the damage?
• Some of the brain defects in schizophrenia apparently
stem from problems during pregnancy or at the time
of birth.
• Prenatal problems include
– Physical complications of mother and fetus
– Emotional stresses on the mother.
• Birth and pregnancy complications associated with
– Brain deficits
– Enlarged ventricles later in life.
Winter effect?
• More schizophrenics are born during the winter and
spring than during any other time of the year.
• Infants born between January and May
– Experienced second trimester of prenatal development in the fall or
early winter:
– High incidence of infectious diseases.
– Strong evidence that the mother’s exposure to viral infections during
the 4th-6th months of pregnancy increases risk of schizophrenia.
• Prenatal starvation is another pathway to schizophrenia.
– Poor maternal diet
– Issues with metabolizing across placenta