Transcript Fig. 15-20, p. 479

Mood Disorders and Schizophrenia
Biological vs. social models of mental disorders
Depression
Unipolar
Symptoms
Biochemistry: Catecholamines, serotonin,histamine
Treatment: Tricyclics and MAO inhibitors (Prozac)
Bipolar
Symptoms
Biochemistry: Catecholamines and cholinergics
Treatment: Lithium, anticonvulsants
Schizophrenia
Symptoms: Positive & negative
Biochemistry: Excess dopamine
Treatment: Phenothiazines
Mood Disorders
• Major depression - feeling sad and helpless
every day for weeks at a time and includes:
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–
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–
Little energy.
Feelings of worthlessness.
Suicidal thoughts.
Feelings of hopelessness.
Difficulty sleeping.
Difficulty concentrating.
Little pleasure from sex or food.
Mood Disorders
• Similar symptoms can result from hormonal
problems, head injuries, brain tumors, or other
illnesses.
• Often comorbid with other disorders such as
schizophrenia, substance abuse, anxiety or
Parkinson’s.
• Absence of happiness is more reliable symptom
than increased sadness.
• Occurs at any age.
• Twice as common in women and about 10%
lifetime prevalence.
Mood Disorders
• Studies of twins and adopted children suggest
moderate heritability.
• Some genes associated with depression are also
associated with anxiety disorders, ADD, OCD,
substance-abuse disorders, bulimia, migraine
headaches, irritable bowel syndrome, and several
other conditions.
• Risk elevated among relatives of women with
early-onset depression (before 30).
Mood Disorders
• Predisposition depends on a variety of
genes.
• One identified gene leads to an 80%
decrease in the brain’s ability to produce
serotonin.
– Most depressed people do not have this gene.
– Those who have the gene have a higher
predisposition.
Mood Disorders
• Another gene controls the serotonin
transporter protein.
– Protein controls the ability of the axon to
reabsorb the neurotransmitter after its release.
• Two “short forms” of the gene are
associated with increased likelihood of
depression after stressful events.
– Perhaps alters the way people react to stressful
events.
Mood Disorders
• Specific hormones are also involved with
depression.
• A likely trigger for an episode of depression is
stress and the release of cortisol.
• Prolonged elevated levels exhaust the body’s
energy, impair sleep and immune function.
– Set the stage for an episode of depression.
Fig. 15-6, p. 460
Mood Disorders
• Postpartum depression is depression after giving
birth.
• Affects about 20% of mothers. Most recover
quickly.
• .1% enter a serious, long-lasting depression.
• More common among women who:
– have suffered depression at other times.
– experience sever discomfort during the times around
menstruation.
• May be associated with a drop in estradiol and
progesterone levels.
Mood Disorders
• Childhood depression is equally common in both
boys and girls.
• After puberty, depression is twice as common in
females.
• The finding is consistent across cultures,
suggesting a biological factor.
Mood Disorders
• Depression is associated with the following :
– Decreased activity in left prefrontal cortex.
– Increased activity in right prefrontal cortex.
• Many people become seriously depressed after
left-hemisphere damage.
• Occasionally, people with right hemisphere
damage become manic.
Mood Disorders
• Some cases of depression may be linked to viral
infection.
• Borna disease is an infection with behavioral
effects of periods of frantic activity alternating
with periods of inactivity.
• Found in a variety of species of animals.
• Found more commonly in depressed people or
people with bipolar.
• Predisposes people to various psychiatric
disorders.
Depression
A more accurate name for mood disorders like depression and bipolar
disorder might be hypothalamic-pituitary-adrenal disorders. They affect
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The hypothalamus -- the "main switch" that affects sleep,
hunger, thirst, and sex drive,
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The pituitary gland -- the master gland that controls hormonal
secretions, and
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The adrenal glands -- two glands that affect stress and steroid
hormones, growth, cell repair, sugar consumption, and immune system
functioning.
Mood Disorders
• Categories of antidepressant drugs include:
1.
2.
3.
4.
Tricyclics.
Selective serotonin reuptake inhibitors.
MAOI’s.
Atypical antidepressants.
Fig. 15-9, p. 463
Mood Disorders
• Tricylclics - a category of antidepressant drugs
that prevent the presynaptic neuron from
reabsorbing serotonin, dopamine, or
norepinephrine after release.
– Examples: imipramine (Tofranil)
• Block histamine receptors, acetylcholine
receptors, and certain sodium channels.
• Side-effects include dry mouth, difficulty
urinating, heart irregularities, and possible fatal
overdose potential.
Mood Disorders
• Selective serotonin reuptake inhibitors (SSRIs) - a
class of antidepressant drugs that block reuptake
of the neurotransmitter serotonin.
– Examples: Fluoxetine (Prozac), setraline (Zoloft),
fluvoxamine (Luvox), citalopram (Celexa) and
paroxetine (Paxil).
• Work in a similar fashion to tricyclics but specific
to the neurotransmitter serotonin.
• Mild side effects include nausea, headache and
occasional nervousness.
Mood Disorders
• Monoamine oxidase inhibitors (MAOI’s) - a class
of antidepressant drugs that blocks the enzyme
monoamine oxidase.
• Monoamine oxidase metabolizes catecholimines
and serotonin into inactive forms.
• Blockage of the enzyme results in more
transmitter in the presynaptic terminal available
for release.
• Usually prescribed after SSRI’s and tricyclics.
Mood Disorders
• Atypical antidepressants - a miscellaneous group
of drugs with antidepressant effects and mild side
effects.
– Example: bupropion (Wellbutrin)
• Works by inhibiting reuptake of dopamine and to
some extent norepinephrine but not serotonin.
• Nefazodone is an antidepressant drug which
specifically blocks serotonin type 2A receptors
and also weakly blocks reuptake of serotonin and
norepinephrine.
Mood Disorders
• Exactly how antidepressant drugs work is unclear.
• Antidepressant alter synaptic activity quickly but
the effects on behavior are not derived until weeks
later.
• Reveals depression is not directly and solely the
result of low serotonin levels.
• Blood samples show normal levels of serotonin
turnover in depressed people.
Mood Disorders
• In some depressed people, neurons in the
hippocampus and the cerebral cortex
shrink.
• Behavioral effects of antidepressant drugs
most likely depend on two slow changes in
the brain:
1. Drug increases the release of BDNF which
promotes neuron growth and survival.
2. Desensitize autoreceptors and thereby
increase release of the neurotransmitter.
Mood Disorders
• Electroconvulsive therapy (ECT) is an electrically
induced seizure used for treatment of severe
depression.
• Used with patients who have not responded to
antidepressant medication or are suicidal.
• Applied every other day for two weeks.
• Side effects include memory loss.
– Memory loss can be minimized if shock is localized to
the right hemisphere.
Mood Disorders
• A drawback of ECT is the high risk of relapse.
• Usually accompanied with drug treatment,
psychotherapy and periodic ECT after initial
treatment.
• How exactly ECT relieves depression is unknown.
• Animal studies suggest an altering of expression
of genes in the hippocampus and frontal cortex.
Mood Disorders
• “Receptive transcranial magnetic stimulation” is
another treatment for depression in which an
intense magnetic field is applied to the scalp, to
stimulate the neurons.
• Like ECT in its level of effectiveness.
• Exact mechanisms of its effects are also unknown.
Mood Disorders
• Disruption of sleep patterns is common in
depression.
– Typically fall asleep but awaken early and are
unable to get back to sleep.
– Enter REM sleep within 45 minutes and have
an increased average number of eye movements
during REM sleep.
• Sleep pattern disruption also increases the
likelihood of depression and is a lifelong
trait of people that are depressed.
Fig. 15-11, p. 466
Mood Disorders
• A night of total sleep deprivation is the quickest
known method of relieving depression.
• Half who experience relief become depressed
again after the next night’s sleep.
• Extended benefits can be derived from altering
sleep schedule on subsequent days.
• Combining sleep alteration with drug therapies
can provide long-lasting benefits.
• Exact mechanism of how sleep disruption relieves
depression is unknown.
Mood Disorders
1. Unipolar disorder is characterized by an
alternating states of normality and
depression.
2. Bipolar disorder (manic-depressive
disorder) is characterized by the
alternating states of depression and mania.
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Mania - restless activity, excitement, laughter,
self-confidence, rambling speech, and loss of
inhibition.
Mood Disorders
• Bipolar disorder I - full blown episodes of mania.
• Bipolar disorder II - milder manic phases, called
hypomania; anxiety and agitation are the primary
symptoms.
• Affects approximately 1% of people.
• Average age of onset is early 20’s.
• Brain’s use of glucose increases during periods of
mania and decreases during periods of depression.
Bipolar Symptoms
A Long-Term Illness That Can Be Effectively Treated
Even though episodes of mania and depression naturally come and go, bipolar disorder is a long-term
illness that currently has no cure. Staying on treatment, even during well times, can help keep the
disease under control and reduce the chance of recurrent, worsening episodes.
Mood Disorders
• Research suggests a heritability for bipolar
disorder (Craddock & Jones, 1999).
• Monozygotic twins share a 50% concordance rate.
• Dizygotic twins, brothers, sisters or children share
a concordance rate of 5-10%.
• Several genes are somewhat more common in
people with the disorder.
• Genes increase the risk but do not cause the
disorder.
Mood Disorders
• Treatments for bipolar include:
1. Lithium - a salt that stabilizes mood and prevents
relapse in mania or depression
2. Drugs - anticonvulsants such as valproate
(depakote) and carbamazepine

Usually prescribed for bipolar II.
• All three drugs block synthesis of arachidonic
acid, which is produced during brain
inflammation.
Mood Disorders
• Seasonal affective disorder (SAD) is depression
that occurs during a particular season.
• SAD Patients have phase-delayed sleep and
temperature rhythms; most depressed people have
phase-advanced patterns.
• Treatment often includes use of very bright lights.
• Most likely explanation is that the light stabilizes
circadian rhythms.
Fig. 15-13, p. 468
Schizophrenia
• Schizophrenia is a disorder characterized by
deteriorating ability to function in everyday
life and some combination of:
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Hallucinations.
Delusions.
Thought disorder.
Movement disorder.
Inappropriate emotional expression.
 (DSM IV)
Schizophrenia
• Causes are not well understood but include
a large biological component.
• Symptoms of the disorder can vary greatly.
• Can be acute or chronic:
– Acute - sudden onset and good prospect for
recovery.
– Chronic - gradual onset and a long-term course.
Schizophrenia
• Two clusters of positive symptoms of
schizophrenia:
1. Psychotic
2. Disorganized
Schizophrenia
•Two clusters of positive symptoms:
1. Psychotic - delusions and hallucinations.
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Delusions: unfounded beliefs
Hallucinations: abnormal sensory experiences
associated with increased activity in
hypothalamus, hippocampus and cortex
2. Disorganized - inappropriate emotional
displays, bizarre behaviors and thought
disorders (difficulty using and
understanding abstract concepts).
Schizophrenia
• Negative symptoms are behaviors that are
absent that should be present.
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Weak social interaction.
Emotional expression.
Speech.
Working memory.
• Negative symptoms are usually stable over
time and difficult to treat.
Schizophrenia
• affects about 1% of the population and ranges in
severity.
• Occurs in all parts of the world, but 10 to 100
times more common in the US and Europe than in
third-world countries.
• More common in men than in women by a ratio of
about 7 to 5.
• More severe and earlier onset for men (early 20s
versus late 20s).
• Likelihood increases as age of father at birth
increases.
Schizophrenia
• Twin studies suggest a genetic component.
• Monozygotic twins have higher concordance rate
(agreement) than dizygotic twins.
• monozygotic twins have a 50% concordance rate.
– Other factors may explain the difference.
• Greater similarity between dizygotic twins than
siblings suggests a prenatal/postnatal
environmental effect.
Fig. 15-14, p. 472
Schizophrenia
• Adopted children studies suggest a genetic role,
but prenatal environment of the biological mother
can not be discounted.
• Attempts to link adult-onset schizophrenia to a
gene have provided inconsistent results.
• Research has identified a gene for child-onset
schizophrenia but cases are rare.
• Schizophrenia most likely depends on a
combination of genes or different genes in
different families.
Schizophrenia
• One study identified a gene linked to high levels
of negative symptoms (Fanous et al., 2005).
• Perhaps genetic research should focus on specific
aspects of schizophrenia rather than schizophrenia
in general.
• Schizophrenia most likely results from
environmental factors in addition to biological
factors.
Schizophrenia
• The neurodevelopmental hypothesis suggests
abnormalities in the prenatal or neonatal
development of the nervous system.
• Leads to subtle abnormalities of brain anatomy
and major abnormalities in behavior.
• Abnormalities could result from genetics,
difficulty during birth, or combination of both.
Schizophrenia
• Supporting evidence for the
neurodevelopmental hypothesis:
– Several kinds of prenatal or neonatal difficulties
are linked to later schizophrenia.
– People with schizophrenia have minor brain
abnormalities that originate early in life.
• Abnormalities of early development could
impair behavior in adulthood.
Schizophrenia
• Prenatal risk factors increasing the
likelihood of schizophrenia include:
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Poor nutrition of the mother during pregnancy.
Premature birth.
Low birth weight.
Complications during delivery.
• Head injuries in early childhood are also
linked to increased incidence of
schizophrenia.
Schizophrenia
• Mother/child blood type differences increase the
likelihood of schizophrenia.
• If the mother has a Rh-negative blood type and the
baby is Rh-positive, the child has about twice the
probability of developing schizophrenia.
Schizophrenia
• Certain viral infections may be an alternative or
supplement genetic influences.
• The season-of-birth effect: tendency for people
born in winter to have a 5% to 8% greater
probability of developing schizophrenia.
– More pronounced in latitudes far from the equator.
– Might be explained by complications of delivery,
nutritional factors, or increased likelihood of viral
infections
Schizophrenia
• Schizophrenia is associated with mild brain
abnormalities:
– Strongest deficits found in the left temporal and frontal
lobe of the cortex.
– Larger than normal ventricles.
 Especially common in those with complications during birth.
• Areas that mature slowly such as the dorsolateral
prefrontal cortex.
– Schizophrenics have deficits in working memory.
Fig. 15-15, p. 474
Schizophrenia
• At a microscopic levels, smaller cell bodies than
usual, especially in hippocampus and prefrontal
cortex.
• Differences in lateralization include the right
planum temporale of the temporal lobe being the
same size or larger than the left.
– Usually the right side is larger.
• Also lower than normal overall activity in the left
hemisphere, suggesting subtle changes in early
development.
Schizophrenia
• Overall, abnormalities are small and vary from
person to person.
• Reasons behinds brain abnormalities are not
certain.
– May be due to substance abuse.
• Results are inconclusive if brain damage
associated with schizophrenia is progressive.
Schizophrenia
• typically develops after age 20; many show signs
earlier.
– Deficits in attention, memory and impulse control.
• Prefrontal cortex may not show signs of damage
until later.
– Structure matures slowly and does not do much at an
earlier age.
– Neurodevelopmental hypothesis is thus plausible but
not firmly established.
Fig. 15-17, p. 476
Schizophrenia
• Antipsychotic/neuroleptic drugs tend to relieve
schizophrenia and similar conditions.
• Chlorpromazine (thorazine) relieves positive
symptoms of schizophrenia.
– Relief usually experienced 2-3 weeks after starting the
drug, which must be taken indefinitely.
Schizophrenia
• chemical families of drugs used to treat
schizophrenia include:
1. Phenothiazines - includes chlorpromazine
2. Butyrophenones - includes halperidol
(Haldol)
• Both block dopamine synapses.
Fig. 15-18, p. 477
Schizophrenia
• The dopamine hypothesis of schizophrenia
suggests that schizophrenia results from excess
activity at dopamine synapses.
• Substance-induced psychotic disorder is
characterized by hallucinations and delusions
resulting from repeated large doses of
amphetamines, methamphetamines, or cocaine.
– Each prolongs activity of dopamine at the synapse,
providing further evidence for dopamine hypothesis.
Schizophrenia
• Research indicates increased activity
specifically at the D2 receptor.
• Limitations of the dopamine hypothesis:
– Direct measurement of dopamine and its
metabolites indicate generally normal levels in
schizophrenics.
– Antipsychotic drugs block dopamine within
minutes but effects on behavior gradually build
over 2 to 3 weeks.
Schizophrenia
• The glutamate hypothesis of schizophrenia
suggests the problem relates partially to deficient
activity at glutamate receptors.
– Especially in prefrontal cortex.
• In many brain areas, dopamine inhibits glutamate
release or glutamate stimulates neurons that inhibit
dopamine release.
• Increased dopamine thus produces the same
effects as decreased glutamate.
Fig. 15-19, p. 479
Schizophrenia
• Schizophrenia is associated with lower than
normal release of glutamate and fewer
receptors in prefrontal cortex and
hippocampus.
• Further support comes from the effects of
phencyclidine (PCP/angel dust).
– Inhibits the NMDA glutamate receptors.
– Produces positve and negative symptoms at
high doses.
Schizophrenia
• The mesolimbocortical system is a set of
neurons that project from the midbrain
tegmentum to the limbic system.
– Site where drugs that block dopamine synapses
produce their benefits.
• Drugs also block dopamine in the
mesostriatal system, which projects to the
basal ganglia.
– Result is tardive dyskinesia, characterized by
tremors and other involuntary movements.
Fig. 15-20, p. 479
Schizophrenia
• Second-generation antipsychotics (atypical
antipsychotics) are a class of drugs used to treat
schizophrenia but seldom produce movement
problems.
– Examples: clozapine, amisulpride, risperidone,
olanzapine, aripiprazole.
• More effective at treating the negative symptoms
and are now more widely used.
• Have less effect on dopamine D2 receptors and
more strongly antagonize serotonin type 5-HT2
receptors.
Schizophrenia
• Schizophrenia cannot be explained by a single
gene or single transmitter.
• Dopamine and glutamate may play important roles
in schizophrenia to different degrees in different
people.
• Schizophrenia involves multiple genes and
abnormalities in dopamine, glutamate, serotonin
and GABA.