Chapter 15Psychological 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 child-onset 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.