1. Chapter 16
Schizophrenia and Affective Disorders

2.  Schizophrenia
 Description
 Schizophrenia:
• A serious mental disorder characterized by:
Disordered thoughts
Delusions of persecution or grandeur
Hallucinations (mostly auditory)
Behaviors (withdrawn or detached, odd
movements))

3.  Schizophrenia
 Description
 Positive symptom: (known by their presence)
• delusions, hallucinations, abnormal movements,
or thought disorders.
 Negative symptom: (characterized by absence)
• social withdrawal, lack of affect, and reduced
motivation.

4.  Schizophrenia
 Possible Causes:
• Heritability is a statistical concept that estimates the
relative contribution of genetic factors to variability in a
trait (e.g., schizophrenia). It is not a measure of the
amount of contribution (e.g., 60% genes vs 40%
environment).
• Heritability: In its simplest form, if schizophrenia were
determined by a single dominant gene, about 75% of
children from schizophrenic parents would get it. If it was
recessive, about 50% would inherit the disorder. An
incidence less than 50% suggests that the disease is
determined by multiple genes and that only a
susceptibility is passed on.

5.  Schizophrenia
 Evidence for heritability
• Concordance rates:
Most studies suggest between 25-40%
concordance in identical twins and about 5-
20% in fraternal twins.
Clearly, the environment is an important
contribution.

6.  Schizophrenia
 Biochemical Causes
• Dopamine Hypothesis: schizophrenia is caused
by excessive dopamine activity in the mesolimbic
system.
• Supporting evidence: drug treatment,
amphetamine psychosis, treatment for
Parkinson’s disease
• Additional evidence: increased DA activity,
increased D3 & D4 receptors in mesolimbic
system,

7.  Schizophrenia
 Pharmacology of Schizophrenia
 Chlorpromazine: A phenothiazine
• A “typical neuroleptic”; a nonspecific dopamine
receptor blocker; first prescribed
antischizophrenic drug.
 Clozapine:
• An “atypical neuroleptic”; an antipsychotic drug
that blocks D4 receptors in the nucleus
accumbens. Little effect on D2 receptors

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10.  Schizophrenia
 Consequences of Long-Term Drug Treatment of
Schizophrenia
 Tardive dyskinesia:
• A movement disorder that can occur after
prolonged treatment with antipsychotic
medication, characterized by involuntary
movements of the face and neck.
 Supersensitivity:
• The increased sensitivity of neurotransmitter
receptors; caused by damage to the afferent
axons or long-term blockage of neurotransmitter
release.

11.  Schizophrenia
 Evidence for neurological abnormalities Negative
symptoms
 Schizophrenics with negative symptoms have
similar symptoms as those with fromtal lobe
damage.
• Frontal lobe size
• Ventrical size
• Cerebral gray matter decreases

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14.  Schizophrenia
 Possible Causes of the Brain Abnormalities
 Epidemiology:
• The study of the distribution and causes of
diseases in populations.
• Research suggest several environmental factors:
-Season of birth: greatest during winter months
-Viral epidemics: associated with viral diseases
-Latitude: increased incidence further from equator
-Prenatal malnutrition: ?
-Rh incompatibility: ?
-Maternal stress: ?

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19.  Schizophrenia
 Degenerative process or sudden cell loss?
• Woods (1998) found that the cell loss in schizophrenic patients
appears to occur suddenly during late adolescence or early
adulthood. Schizophrenia is not a gradual degenerative disease like
Parkinson’s or Alzheimer’s diseases.
• Does not appear to involve cell death and ‘gliosis’ (replacement of
neural tissue by glia).
• Appears to involve loss of dendrites. Areas of tissue loss are
correlated with symptoms (temporal lobes with auditory
hallucinations, for example).
• The frontal cortex seems to be involved in most cases of
schizophrenia (hypofrontality)

20.  Schizophrenia
 The cause of schizophrenia now appears to be a
disturbance of normal brain development.
• Genetic predisposition may make individuals more
susceptible
• Obstetric complications may cause individuals without
genetic predisposition to develop schizophrenia

21.  Schizophrenia
 Hypofrontality (caused by a reduction in cell volume in the dorsolateral
frontal cortices) is associated with negative symptoms of schizophrenia.
 Hypofrontality also results in an increase in dopamine activity in the
mesolimbic system which is associated with positive symptoms.
 Dopamine hypothesis suggests that hypofrontality results in a disruption
of normal glutamate activity from the frontal cortex to the mesolimbic
system.
 NMDA agonists cannot be used because they would cause seizures, but
glycine may be effective in treating schizophrenics since it is also an
NMDA agonist. Several studies have shown good results with negative
symptoms

22.  Major Affective Disorders
 Description
 Major affective disorder:
• A serious mood disorder; includes major
depressive disorder and bipolar disorder.
• May effect as many as 5% of US population in a
given year. Perhaps as many as 25% over
lifetime.

23.  Major Affective Disorders
 Description
 Major depressive disorder:
• A serious mood disorder that consists of
unremitting depression or periods of depression
that do not alternate with periods of mania.
 Bipolar disorder:
• A serious mood disorder characterized by
cyclical periods of mania and depression.

24.  Major Affective Disorders
 Causes of Depression
 Genetic contributions:
• Bipolar disorder may be caused by a single
dominant gene.
Location still not confirmed, but heritability
studies reveal strong link.
 Major depressive disorder:
• Less likely caused by single gene than bipolar
disorder.
• Amine hypothesis: deficiencies in activity of one
or several amine neurotransmitter systems (NE,
SE)

25.  Major Affective Disorders
 Drug Treatment for Depression
 Tricyclic antidepressants:
• A class of drugs used to treat depression; inhibits the
reuptake of norepinephrine and serotonin; named for the
specific molecular structure.
Amitriptyline (Elavil)
 Monoamine oxidase inhibitors (MAOIs):
• Prevent degradation of NT in synapse.
phenelzine (Nardil)
 Serotonin specific reuptake inhibitor (SSRI):
• A drug that inhibits the reuptake of serotonin without
affecting the reuptake of other neurotransmitters.
fluoxetine (Prozac)

26.  Major Affective Disorders
 Physiological Treatments
 Lithium
• A chemical element; lithium carbonate is used to
treat bipolar disorder
 Carbamazepine:
• An anticonvulsive drug (trade name: Tegretol)
that is used to treat seizures originating from a
focus, also used to treat mania in bipolar
disorder.

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28.  Major Affective Disorders
 Physiological Treatments
Electroconvulsive therapy (ECT):
• A brief electrical shock that induces a seizure;
used therapeutically to alleviate severe
depression when medication is not effective.
Transcranial Magnetic Stimulation (TMS):
Magnetic field causes a weak electrical field and
electrical current within the brain. Has been
useful in some cases of depression.

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30.  Major Affective Disorders
 Evidence of Brain Abnormalities
 Brain abnormalities:
• Research suggests abnormalities in the
prefrontal cortex, basal ganglia, hippocampus,
thalamus, cerebellum, and temporal lobes.
• Some evidence suggests increased size of the
cerebral ventricles may suggest the loss of
neural tissue.

31.  Major Affective Disorders
 Evidence of Brain Abnormalities
 Silent cerebral infarction (SCI):
• A small cerebrovascular accident (stroke) that
causes minor brain damage without producing
obvious neurological symptoms.

32.  Major Affective Disorders
 Role of Circadian Rhythms
 REM Sleep Deprivation:
• Selective deprivation of REM sleep through EEG
monitoring, is one of the most effective
antidepressant treatments; suggests a close
relationship between REM sleep and mood.
• Antidepressant effects require several weeks of
deprivation.

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36.  Major Affective Disorders
 Role of Circadian Rhythms
 Total Sleep Deprivation:
• Total sleep deprivation has antidepressant effect
that are immediate; however, the procedure is
not very practical.
• Some individuals do not respond to total or
selective sleep deprivation.

37.  Major Affective Disorders
 Role of Zeitgebers
 Seasonal affective disorder (SAD):
• A mood disorder characterized by depression,
lethargy, sleep disturbances, and craving for
carbohydrates during the winter months.
 Summer depression:
• A mood disorder characterized by depression,
sleep disturbances, and loss of appetite.

38.  Major Affective Disorders
 Role of Zeitgebers
 Phototherapy:
• Treatment of seasonal affective disorder by daily
exposure to bright light.