Transcript Chapter 15 Psychological Disorders

Chapter 15
Psychological Disorders
Mood Disorders
• Mental illness results from the combination of
biological predisposition and experiences.
– Both play an important role.
• A solid understanding of both aspects is
necessary for successful treatment.
Mood Disorders
• Major depression - feeling sad and helpless
everyday for weeks and includes the
following characteristics (DSM-IV):
– Little energy.
– Feelings of worthlessness.
– Suicidal thoughts.
– Feelings of hopelessness.
– Difficulty sleeping.
– Difficulty concentrating.
– Little pleasure
Mood Disorders
• Similar symptoms can result from hormonal
problems, head injuries, brain tumors,
substance abuse, or other illnesses.
• Absence of happiness is more reliable
symptom than increased sadness.
• Occurs at any age, but uncommon in children
• Twice as common in women
• 10% lifetime prevalence.
Mood Disorders
• Studies of twins and adopted children
suggest a moderate degree of heritability.
• Some of the 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 is elevated among relatives of women
with early-onset depression (before 30).
Mood Disorders
• Predisposition depends on a variety of genes.
• Effects of these genes have varied between
studies
Mood Disorders
• One gene identified controls the serotonin
transporter protein.
– controls the ability of the axon to reabsorb
the neurotransmitter after its release.
• Two “short forms” of the gene are associated
with an increased likelihood of depression
after stressful events.
– May alters people’s reactions to stressful
events or make them more sensitive to
environmental influences
Mood Disorders
• A few cases of depression are linked to viral
infections.
• Borna disease is a viral infection which may
predispose people to depression
• Illustrates that many different causes can lead
to similar behavioral results
Mood Disorders
• Postpartum depression is depression after
giving birth.
• Affects about 20% of women and most
recover quickly
• More common among women who have
suffered depression at other times.
• May be associated with a drop in estradiol
and progesterone levels.
• Testosterone drop in men also associated
with increased probability
Mood Disorders
• Depression is also associated with the
following brain activity:
– Decreased activity in the left prefrontal
cortex.
– Increased activity in the right prefrontal
cortex.
Mood Disorders
•
Many drugs used to treat psychiatric
disorders discovered by accident
• Categories of antidepressant drugs include:
1. Tricyclics.
2. Selective serotonin reuptake inhibitors.
3. MAOI’s.
4. Atypical antidepressants.
Mood Disorders
• Tricylclics - operate by blocking transporter
proteins that reabsorb serotonin, dopamine,
and norepinephrine into the presynaptic
neuron after release.
– Examples: imipramine (Tofranil)
• Also block histamine receptors, acetylcholine
receptors, and certain sodium channels.
– Creates side-effects (dry mouth, difficulty
urinating, heart irregularities)
Mood Disorders
• Selective serotonin reuptake inhibitors
(SSRIs) - works by blocking the 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 are
specific to the neurotransmitter serotonin.
• Milder side effects but same effectiveness
Mood Disorders
• Monoamine oxidase inhibitors (MAOI’s) blocks the enzyme monoamine oxidase that
metabolizes catecholimines and serotonin
into inactive forms.
• Blockage of the enzyme results in more of the
transmitters in the presynaptic terminal
available for release.
• Usually prescribed if SSRI’s and tricyclics are
not effective.
Mood Disorders
• Atypical antidepressants - a miscellaneous
group of drugs with antidepressant effects
and mild side effects.
– Example: bupropion (Wellbutrin)
– Works by inhibiting the reuptake of
dopamine and to some extent,
norepinephrine but not serotonin.
Mood Disorders
• St. Johns’ wort is an herb that is often used
as a treatment for depression by many.
• Marketed as a nutritional supplement and not
regulated by the FDA.
• Believed to work in the same way as SSRI’s
but effectiveness is controversial.
• Increases the effectiveness of a liver enzyme
that can decrease the effectiveness of other
medications.
Mood Disorders
• Studies indicate half of people show a good
response within weeks after use of
antidepressant drugs
• About same percentage respond to therapy
• 30% respond to a placebo
• Combination of both benefits only a slightly
higher percentage
• Little difference regarding the various types of
antidepressant drug
Mood Disorders
• Benefits of antidepressant is greatest for
people with severe depression.
• Antidepressants are generally ineffective for
people who suffered abuse, neglect, or other
trauma during early childhood.
– Usually respond better to psychotherapy
• Use of antidepressants in children
controversial
• Most studies found ineffective and can
sometimes increase suicidal thoughts
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
often take longer than the effect on our
neurochemisrty which happen within hours
One explanation is that antidepressant
drugs increases the release of BDNF which
promotes neuron growth and survival.
Mood Disorders
• Electroconvulsive therapy (ECT) is an
electrically induced seizure that is used for
the treatment of severe depression.
• Used with patients who have not responded
to antidepressant medication or are suicidal.
• Applied every other day for a period of 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.
• altering of the expression of genes in the
hippocampus and frontal cortex is suggested.
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.
Mood Disorders
• A night of total sleep deprivation is the
quickest method of relieving depression.
• Increases proliferation of new neurons in the
hippocampus
• Half become depressed again after the next
night’s sleep.
• Extended benefits derived from altering sleep
schedule on subsequent days and combining
sleep alteration with drug therapies
• Exact mechanism are not unknown.
Mood Disorders
• Hormone leptin has shown some promise as
an alternative treatment.
• Regular exercise is also effective.
• Increases blood flow to the brain.
• Reduces the effects of stress.
• Can be combined with other treatments to
magnify benefits.
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.
– Mania - restless activity, excitement,
laughter, self-confidence, rambling
speech, and loss of inhibition.
Mood Disorders
• Bipolar disorder I - characterized by full blown
episodes of mania.
• Bipolar disorder II - characterized by much
milder manic phases, called hypomania, of
which anxiety and agitation are the primary
symptoms.
• Each approximately 1% of people.
• Average age of onset is in the early 20’s.
• Brain’s use of glucose increases during
periods of mania and decreases during
periods of depression.
Mood Disorders
• Research suggests a heritability basis for
bipolar disorder (Craddock & Jones, 1999).
• Twin studies suggest monozygotic twins
share a 50% concordance rate.
• Dizygotic twins, brothers, sisters or children
share a concordance rate of 5-10%.
• Comparison of chromosomes have identified
several genes that are somewhat more
common in people with the disorder.
• Genes simply 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 - anticonvulsant drugs such as
valproate (depakote) and carbamazepine
• Drugs work by:
• decreasing glutamate activity
• blocking the synthesis of the brain chemical
arachidonic acid, which is produced during
brain inflammation.
Mood Disorders
• Seasonal affective disorder (SAD) is a form of
depression that regularly occurs during a
particular season.
• Patients with SAD have phase-delayed sleep
and temperature rhythms; most depressed
people have phase-advanced patterns.
• Treatment often includes the use of very
bright lights.
• Most likely explanation is that the light affects
serotonin synapses and alters circadian
rhythms.
Schizophrenia
• Schizophrenia is a disorder characterized by
deteriorating ability to function in every day
life and some combination of the following:
– 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 either acute or chronic:
– Acute - condition has a sudden onset and
good prospect for recovery.
– Chronic - condition has a gradual onset
and a long-term course.
Schizophrenia
•
Positive symptoms are behaviors that are
present that should be absent
• Two cluster of positive symptoms of
schizophrenia include:
1. Psychotic
2. Disorganized
Schizophrenia
1. Psychotic - consists of delusions and
hallucinations.
– Delusions: unfounded beliefs
– Hallucinations: abnormal sensory
experiences associated with increased
activity in the thalamus, 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.
– Weak social interaction.
– Emotional expression.
– Speech.
– Working memory.
• Negative symptoms are usually stable over
time and difficult to treat.
Schizophrenia
• Schizophrenia affects about 1% of the
population and range in severity.
• Occurs in all parts of the world, but is 10 to
100 times more common in the United States
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 age of onset for men
(early 20’s versus late 20).
– May be related to release of dopamine
Schizophrenia
• Twin studies suggest a genetic component,
but does not depend on a single gene.
• Monozygotic twins have a much higher
concordance rate (agreement) than dizygotic
twins.
• But monozygotic twins only have a 50%
concordance rate.
– Other factors may explain the difference.
• Greater similarity between dizygotic twins
than siblings suggests a prenatal/postnatal
environmental effect.
Schizophrenia
• Adopted children studies suggest a genetic
role, but prenatal environment of the
biological mother can not be discounted.
• Attempt to schizophrenia to an identified gene
have provided inconsistent results.
• Research has identified a gene for childonset schizophrenia but cases are rare.
• Schizophrenia most likely depends on a
combination of genes or different genes in
different families.
Schizophrenia
• Researchers have identified more than a
dozen genes that appear to be more common
in people with schizophrenia.
• DISC1 (disrupted in schizophrenia 1) gene
controls the rate of generation of new
neurons in the hippocampus.
• Another gene important for brain plasticity
and development.
• New gene mutations are also an explanation.
(microdeletions and microduplications more
common)
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,
trouble during prenatal development, birth, or
early postnatal development.
• Environmental influences later in life
aggravate the symptoms.
Schizophrenia
• Supporting evidence for the
neurodevelopmental hypothesis includes:
– 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
• Risk factors increasing the likelihood include:
– Poor nutrition of the mother during
pregnancy.
– Premature birth.
– Low birth weight.
– Complications during delivery.
– Head injuries in early
– Extreme stress of mother during pregnancy
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.
– Response weak in first child but stronger in
later pregnancies
Schizophrenia
• The season-of-birth effect refers to the
tendency for people born in winter to have a
slightly (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 infection in mother
Schizophrenia
• Viral infections in mother can:
• Increase cytokines in mother that impair brain
development of fetus
• Cause fever which damages the fetal brain
• Other infections during childhood can also
increase risk
– Taxoplasma gondii
Schizophrenia
• Associated with mild brain abnormalities:
– Strongest deficits found in the left temporal
and frontal lobe of the cortex.
– Thalamus smaller than average
– Larger than normal ventricles (especially
common in those with complications during
birth)
– dorsolateral prefrontal cortex (areas that
mature slowly)
• Schizophrenics have deficits in working
memory and attention.
Schizophrenia
• At a microscopic levels, smaller cell bodies
than usual, especially in the 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.
• No sign of neuron death
Schizophrenia
• Schizophrenia typically develops after the
age of 20 but many show sign at an earlier
age.
– Deficits in attention, memory and impulse
control.
• Prefrontal cortex damage 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.
Schizophrenia
• Antipsychotic/neuroleptic drugs are drugs that
tend to relieve schizophrenia and similar
conditions.
• Chlorpromazine (thorazine) is a drug used to
treat schizophrenia that relieves the positve
symptoms of schizophrenia.
– Relief usually experienced 2-3 weeks after
taking the drug, which must be taken
indefinitely.
Schizophrenia
•
Two chemical families of drugs used to treat
schizophrenia include:
1. Phenothiazines - includes chlorpromazine
2. Butyrophenones - includes halperidol
(Haldol)
• Both drugs block dopamine synapses.
Schizophrenia
• The dopamine hypothesis of schizophrenia
suggests that schizophrenia results from
excess activity at dopamine synapses in
certain areas of the brain.
• 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
include the following:
– Direct measurement of dopamine and its
metabolites indicate generally normal
levels in people with schizophrenia.
– 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 the 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.
Schizophrenia
• Schizophrenia is associated with lower than
normal release of glutamate and fewer
receptors in the prefrontal cortex and
hippocampus.
• Further support comes from the effects of
phencyclidine (PCP/angel dust).
Schizophrenia
• Effects of phencyclidine (PCP) support
glutamate hypothesis.
• Low doses produce intoxication and slurred
speech
• Larger doses produce positve and negative
symptoms
• Produce little psychotic responses in
preadolescents
• produces relapse in people with prior
schizophrenia
• Glycine increases effectiveness of glutamate
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 project to the
basal ganglia.
– Result is tardive dyskinesia, characterized
by tremors and other involuntary
movements.
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.