Biopsychology of Psychiatric
Disorders
Ch. 18 (cont’d)
Outline
• Schizophrenia (cont’d)
– Dopamine Theory of Schizophrenia
• Affective Disorders
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Symptoms and Etiology
Antidepressant Drugs
Monoamine Theory of Depression
Diathesis Model of Depression
Dopamine Theory of
Schizophrenia
• Side effects of chlorpromazine and
reserpine are mild tremors at rest,
muscular rigidity, and a decrease in
voluntary movement
Dopamine Theory of
Schizophrenia
• These side effects are the same as the
symptoms of Parkinson’s Disease
• Thus, neurochemical changes that were the
basis of these drug’s antischizophrenic
action were related to pathology underlying
Parkinson’s symptoms
Dopamine Theory of
Schizophrenia
• Parkinson’s disease is associated with
dopamine deficiency
• It seemed that chlorpromazine and reserpine
reduced brain dopamine levels
• And reduction of dopamine was alleviating
schizophrenia symptoms
Dopamine Theory of
Schizophrenia
• On the basis of these two inferences it was
proposed that schizophrenia is associated
with excessive activity in the
dopaminergic systems in the brain
Dopamine Theory of
Schizophrenia
• Two previous findings lent additional
support to the dopamine theory of
schizophrenia:
Dopamine Theory of
Schizophrenia
– Reserpine was known to be a dopamine
antagonist (it depleted the brain of dopamine
by causing them to leak from their vessicles)
– Stimulants, which are agonists of dopamine
trigger schizophrenic episodes in healthy
subjects at high doses (cocaine psychosis and
amphetamine psychosis)
Dopamine Theory of
Schizophrenia
• Additional research clarified that although
chlorprozamine is a antagonist like
reserpine, left dopamine levels unchanged;
• Rather it acts as a false transmitter chlorpromazine acts like dopamine and is
received by dopaminergic membrane
receptors (antagonistic)
Dopamine Theory of
Schizophrenia
• More than one type of dopaminergic
receptor; total of five types
• Found that antischizophrenic drug
haloperidol binds to D2 only; while
chlorpromazine binds to both D1 and D2
Dopamine Theory of
Schizophrenia
• Dopamine theory of schizophrenia is
revised; schizophrenia can now be viewed
as caused by excess activity at D2
receptors and thus alleviated by drugs that
block activity at D2 receptors
Dopamine Theory of
Schizophrenia
• Four questions about this theory that have
yet to be resolved:
Four questions about DTS
• Are D2 receptors the only ones involved in
schizophrenia?
– The effectiveness of clozapine, which binds
poorly to D2 receptors yet binds to serotonin
receptors suggest that serotonin receptors may
be involved in schizophrenia
Four questions about DTS
• Why does it take several weeks for
neuroleptics to work?
– The therapeutic effect of blockade is mediated
by neural adaptation (slow compensatory
changes) to the blockade of dopamine
receptors, rather than by the blockade itself
Four questions about DTS
– One hypothesis is that prolonged neuroleptic
treatment eventually produces depolarization
blockade in dopamine neurons, and it is this
decrease in activity that is related to the drug’s
therapeutic effect
Four questions about DTS
• What parts of the brain are involved in
schizophrenia?
– Imaging studies have revealed many changes,
including small cerebral cortices and large
ventricles
Four questions about DTS
– The cortical abnormalities are most prevalent in
the prefrontal (organization of thoughts),
cingulate (emotion), and temporal (auditory
stimui) cortices
Four questions about DTS
– Some evidence that schizophrenia is a
neurodevelopmental disorder; there is no
obvious ongoing degeneration in the brain of
schizophrenic patients, and the pathology is
observed in largely developed by the time
diagnosis is first made
Four questions about DTS
• Why are neuroleptics effective against only
some of the symptoms of schizophrenia?
– current hypothesis is that:
• Cases with positive symptoms (hallucinations,
delusions, incoherence) are caused by excess D2
activity and are helped
• Negative symptoms (catatonia, blunt affect, poverty
of speech) are due to permanent brain damage and
cannot be helped
Schizophrenia
• Video shown in class
– Individuals affected with Schizophrenia
– Cell migration and aggregation hypothesis
Affective Disorders
• Individuals in whom sadness and apathy is
so severe and frequent that it interferes with
functioning are said to be suffering from the
psychiatric disorder of depression
• The opposite of this is mania
Symptoms of Depression
• Intense feelings of despair, hypoactivity,
sleep problems, withdrawal, lack of
appetite, and lack of hygiene
Symptoms of Mania
• Individuals are overconfident, impulsive,
distractible, and highly energetic
Symptoms of Affective Disorders
• Bipolar affective illness - suffer from
mania and depression
• Unipolar affective illness - suffer from
depression
Etiology of Affective Disorders
• Genetic basis - concordance rate for bipolar
for identical twins is 60%; 15% for fraternal
twins
• Depression can be reactive (stress from
negative experience) or endogenous (no
apparent external triggers)
Etiology of Affective Disorders
• Some indication that early exposure to
stress increases the likelihood of developing
depression in adulthood
Antidepressant Drugs
• Monamine Oxidase Inhibitors (MAO
inhibitors) increase level of monoamines
(norepinephrine and serontonin) by
stopping activity of enzymes that break
down monoamine neurotransmitters in the
presynaptic cell (before they are released)
(agonistic)
• For unipolar affective disorder
Antidepressant Drugs
• Tricyclic Antidepressants block the
reuptake of both serontonin and
norepinephrine (agonistic)
• For unipolar affective disorder
Antidepressant Drugs
• Lithium is a metalic ion
• Used to treat bipolar affective disorder
Antidepressant Drugs
• Selective Monoamine-Reuptake Inhibitors
block reuptake of a specific monoamine NTs
(agonist; unipolar affective disorder)
– Selective serotonin-reuptake inhibitors (SSRIs) such as
Prozac, Paxil, Xoloft, Luvox, Remeron
– Selective norepinephrine-reuptake inhibitors (SNRIs)
such as Reboxetine
– Drugs that block more than one type are Wellbutrin and
Effexor
Theories of Depression
• Monoamine Theory of Depression
• Diathesis - Stress Theory of Depression
Monoamine Theory of
Depression
• Most widely accepted theory
• Based on fact that all clinically effective
drugs are serotonin and/or
norepinephrine agonists;
• Thus depression may be due to
underactivity at serontonin and
norepinephrine synapses
Monoamine Theory of
Depression
• In support of this theory, there is evidence
that certain norepinephrine and serotonin
receptors are elevated in untreated
depressed patients; this may be due to low
levels of transmitters eliciting a
compensatory increase in receptors called
receptor up-regulation
Monoamine Theory of
Depression
• However, this theory cannot explain why
monoamine antidepressants take 3 or more
weeks to take effect although they
immediately increase extracellular
monoamine leels or why serotonin and
norepinephrine agonists are equally
effective
Diathesis-Stress Theory of
Depression
• Based on idea that an individual inherits a
diathesis (genetic predisposition) for
depression; if the individual is stressed early
in life their systems become altered so that
they are hypersensitive to stress the rest of
their lives
• This leads to development of depression