Chapter 14: Psychiatric Disorders

. Substance Abuse
A. Addiction (or dependence) is a paradox, because the pleasures decrease and the risks
increase as the addiction progresses.
B. While we usually talk about drugs and alcohol with regards to addiction, the same
principles are true of other addictions, such as gambling, overeating, excessive video
game playing, and so on.
C. Drug Mechanisms
1. Drugs either facilitate or inhibit transmission at synapses.
a. Antagonists block receptors, while agonists mimic or increase effects of a
neurotransmitter.
b. A drug has an affinity for a receptor if it binds to it.
c. A drug’s efficacy is its tendency to activate the receptor.
D. Predispositions
1. People differ in their predisposition to alcohol or drug abuse.
2. Certain aspects of brain function and behavior are present from the start in people
with a familial disposition to addiction—not all individuals develop addiction.
3. Genetic Influences
a. Twin studies confirm strong influence of genetics on vulnerability to
alcohol/drugs.
b. Many addiction-linked genes have been identified, each with a small effect.
c. People with a gene for producing less acetaldehyde dehydrogenase metabolize
acetaldehyde (from alcohol) more slowly—Those individuals tend to drink less
and have fewer problems with alcohol abuse (eg., China and Japan)
4. Environmental Influences
a. Prenatal alcohol exposure increases risk of alcohol addiction later in life.
b. Children with careful parental supervision are less likely to develop impulse
control problems, even if they have genetic predisposition.
c. Alcoholics that develop alcohol problems before age 25 tend to have family
history and a genetic predisposition and rapid onset of problems.
5. Behavioral Predictors of Abuse
a. Sons of alcoholics show less than average intoxication after drinking a moderate
amount of alcohol, and more decrease in stress as a result of drinking alcohol,
than sons of non-alcoholics.
b. Alcohol decreases stress for most people, but more so for sons of alcoholics.
E. Synaptic Mechanisms
1. Nearly all abused drugs increase activity at dopamine and norepinephrine synapses.
The effects while the drug is in the brain differ from effects that occur during
withdrawal, and effects responsible for cravings.

2. Discovery of neuroanatomy of addiction occurred by accident, when Olds & Milner
missed a target for implanting an electrode in rats. The rats’ self-stimulation of the
brain increased when electrodes were in areas that increased the release of
dopamine or norepinephrine in the nucleus accumbens.
3. Nucleus accumbens reinforces experiences of all types; drugs work to increase
dopamine in that area via direct (stimulants) or indirect (opiates) means.
4. Other experiences that release dopamine in the nucleus accumbens
a. Sexual excitement
b. Music
c. Taste of sugar
d. Imagining something pleasant
e. Habitual gambling and video game playing
5. Dopamine contributes to reinforcement, but no longer appears to be as central as
previously believed
6. Cravings
a. A craving is an insistent search for an activity.
b. An addict can want (crave) something without liking it.
c. Studies with rats show that repeated exposure to addictive substances alters
receptors in nucleus accumbens and other areas so that they become less
responsive to other stimuli and more responsive to addiction-related stimuli.
d. Repeated exposure to addictive drugs also disrupts activity in the prefrontal
cortex, which is responsible for restraining impulses.
7. Tolerance and Withdrawal
a. Tolerance occurs when the effects of a drug (especially the pleasurable effects)
decrease over time.
b. Tolerance is in part learned; when rats are given a drug in a location, their
tolerance is increased in that location.
c. When the body reacts to the absence of a drug, it is called withdrawal.
d. Modified hypothesis: Person with an addiction may use the substance to cope
with stress
F. Treatments
1. Some addicts able to decrease use or quit on their own
2. Alcoholics Anonymous (or similar group)
3. Cognitive-behavioral therapy
4. Medications to Combat Alcohol Abuse
a. Antabuse makes it harder to metabolize acetaldehyde, which causes a person to
feel sick after drinking alcohol.
b. Antabuse is moderately effective as a supplement to a person’s commitment to
stop drinking.
c. Naloxone and naltrexone block opiate receptors and decrease pleasure from
alcohol.
5. Medications to Combat Opiate Abuse
a. Methadone, Buprenorphine, and LAAM are used to reduce withdrawal and
avoid the “high” of heroin and morphine. They do not end opiate addiction, but
satisfy the craving in a less dangerous way.

II. Mood Disorders
A. Major Depressive Disorder
1. Major Depression: People with major depression feel sad, helpless, and lacking in
energy and pleasure for weeks at a time. Individuals with major depression also feel
worthless, have trouble sleeping, cannot concentrate, get little pleasure from sex or
food, may contemplate suicide, and in many cases, can hardly imagine being happy.
They might experience cognitive problems: low motivation, impaired memory,
concentration problems, and impaired sense of smell.
2. Absence of happiness is a more reliable symptom than increased sadness.
3. Studies show that people with major depression reacted normally to sad or
frightening depictions, but seldom smiled at comedies or pleasant pictures. In similar
studies, people with depression show a decreased response to a likely reward.
4. Approximately 5 percent of adults in the United States have a “clinically significant”
depression.
5. Childhood depression is equally common for boys and girls, but beyond age 14,
depression is more common in females.
6. Although some people suffer from long-term depression, it is more common to have
episodes of depression separated by periods of normal mood. Generally, the first
episode is longer than subsequent episodes. The more one experiences an episode,
the easier it is to start another one.
7. Genetics
a. Evidence of genetic or other biological predispositions to depression exist.
b. People with early-onset depression (before age 30) have a high probability of
other relatives with depression, anxiety disorders, ADHD, alcohol or marijuana
abuse, obsessive compulsive disorder, bulimia, migraine headaches, and irritable
bowel syndrome.
c. People with late onset depression (especially after 45 to 50) have a high
probability of relatives with circulatory problems.
d. Hypothesis: The effect of a gene varies with the environment
e. Evidence:
i. Young adults with the short form of the serotonin transporter gene who
experienced stressful experiences had a major increase in probability of
developing depression.
ii. Long form of serotonin transporter gene less susceptible to stressful events;
one long and one short moderate risk.
iii. Short form of serotonin transporter may increase depressive reaction to
stressful events—especially childhood stress.
8. Abnormalities in Hemisphere Dominance
a. Most people suffering from depression have decreased activity in the left
hemisphere and increased activity in the right prefrontal cortex.
B. Antidepressant Drugs
1. Drugs used for the treatment of depression and other mood disorders.
2. Types of Antidepressants
a. Tricyclics: Prevent the presynaptic neuron from reabsorbing catecholamines or
serotonin after releasing them (this allows the neurotransmitter to remain
longer in the synaptic cleft thus stimulating postsynaptic receptors).

b. Selective serotonin reuptake inhibitors (SSRIs): These drugs are similar to
tricyclics, but are specific to the neurotransmitter serotonin. The most popular
drug in this class is fluoxetine (Prozac).
c. Serotonin norepinephrine reuptake inhibitors (SNRIs): Block the reuptake
of serotonin and norepinephrine.
d. Monoamine oxidase inhibitors (MAOIs): Block the enzyme monoamine
oxidase (MAO) from metabolizing catecholamines and serotonin into inactive
forms.
e. Atypical antidepressants: A miscellaneous group of drugs with
antidepressant actions and mild side effects, including bupropion (Wellbutrin),
which inhibits reuptake of dopamine and to some extent norepinephrine.
f. New Investigation: Ketamine
a. Antagonizes NMDA type glutamate receptors
b. Produces rapid antidepressant effects in people who don’t respond to
other medications
c. Not suitable (produces delusions and hallucinations) but may lead to
something similar
g. St. John’s Wort
a. Herb often used as a treatment for depression.
b. Nutritional supplement not regulated by the FDA.
c. Effectiveness about the same as standard antidepressants.
d. Increases the production of a liver enzyme that decreases the
effectiveness of other medications.
3. How are Antidepressants Effective?
a. People with depression have approximately normal levels of release of
neurotransmitters. Some studies show that people with depression have an
increase in serotonin release.
b. Although some patients respond to one drug and not another, we have no clear
evidence that any antidepressant drug produces any different effects from any
other.
c. Antidepressant drugs produce their effects on neurotransmitters in the synapses
within minutes to hours but it takes weeks before patients experience mood
elevation.
d. People with depression have lower than average brain-derived neurotrophic
factor (BDNF): important for synaptic plasticity. As a result, people with
depression show:
e. Smaller than average hippocampus
f. Impaired learning
g. Reduced production of hippocampal neurons.
h. Prolonged use of antidepressants increases BDNF production.
4. How Effective Are Antidepressants?
a. Depression occurs in episodes so even those with untreated depression recover
within a few months.
b. The best comparisons of the benefits of drugs are comparisons between those
who are treated with medication and those who are administered a placebo.
Placebo results often overlap with drug group results. One study suggests that

for people with mild to moderate depression, there is no clear benefit of a drug
over a placebo. Furthermore, even for those with severe depression,
antidepressants don’t always work.
5. Alternatives to Antidepressant Drugs
a. Another type of treatment is Cognitive-Behavioral Therapy. While drugs work
better for dysthymia, therapy works better for those who suffered abuse or
neglect during early childhood. For such cases, antidepressants are usually
ineffectual. Psychotherapy is also more likely to have long term benefits,
reducing the likelihood of relapse.
b. On average, people receiving both treatments improve more than those
receiving one treatment alone.
c. Regular, non-strenuous exercise increases blood flow to the brain and provides
other benefits that are especially helpful to people with depression.
d. Supplements such as Omega-3 fatty acids and B vitamins have been explored,
but research is not conclusive.
e. Electroconvulsive Therapy (ECT)
i. Electroconvulsive therapy (ECT): Inducing seizures with an electric
shock to the head. ECT is usually applied every other day for about two
weeks.
ii. Invented by Ladislas Meduna in the 1930s for schizophrenia, the treatment
was mostly ineffectual on schizophrenia and became overused in the
1950’s on patients without their consent.
iii. One common side effect was memory loss for the few months following
the shock minimized when shock is only to right hemisphere.
iv. About half of those who respond well to ECT relapse into depression
within 6 months unless they are given antidepressant drugs or other
therapies to prevent it.
v. How ECT relieves depression is unknown however; it is known to
proliferate neurons in the hippocampus and increase BDNF.
f. Altered Sleep Patterns
i. Most depressed people have sleep problems, which precede mood
changes.
ii. Most depressed people enter REM sleep within 45 minutes after going to
bed compared to about 80 minutes for non-depressed people and they have
more than the usual number of eye movements during REM sleep. This
pattern resembles someone who has traveled west for a few time zones.
iii. One way to treat depression is to have the depressed person stay awake all
night. Another method is to alternate the sleep schedule. This suggests that
a disrupted circadian rhythm plays a role. Additional evidence for this is
Seasonal Affective Disorder (SAD).
g. Seasonal Affective Disorder
i. Seasonal affective disorder (SAD): Depression that reoccurs seasonally,
usually in the winter.
ii. SAD is most common in regions closest to the poles, where the nights
are very long in winter and very short in summer.

iii. It is possible to treat SAD by exposing the person to very bright lights
for about an hour either early in the morning or in the evening.
iv. Patients with SAD have phase-delayed sleep and temperature rhythms
whereas most depressed people have phase-advanced patterns.
v. Many people with SAD have a mutation on a gene responsible for
regulating circadian rhythms
h. Deep Brain Stimulation
i. Deep brain stimulation consists of a device implanted into the brain to
delivery periodic stimulation to certain brain areas.
ii. Research is still in the experimental phase, but results are promising.
iii. Alternative: optogenic stimulation
C. Bipolar Disorder
1. Depression can be unipolar or bipolar. People with unipolar disorder vary
between depression and normality. People with bipolar disorder (formerly known
as manic-depression disorder) alternate between episodes of depression and mania
(characterized by restless activity, excitement, laughter, self-confidence, rambling
speech, and loss of inhibitions).
2. Bipolar I disorder: A type of bipolar disorder where the person has full-blown
episodes of mania.
3. Bipolar II disorder: A type of bipolar disorder where the person has much milder
manic phases, called hypomania.
4. Genetics
a. There is a strong hereditary basis for bipolar disorder, as shown by twin
studies. Two genes appear to increase the probability of bipolar II disorder.
They have also demonstrated that some of the same genes that predispose
major depression also predispose bipolar disorder.
5. Treatments
a. Lithium salts are the most effective therapy for bipolar disorder, but how it
works remains unknown. Other drug treatments include anticonvulsant drugs
such as valproate and carbamazepine. Encouraging bipolar patients to keep a
consistent sleep schedule may reduce the intensity of the mood swings.
III. Schizophrenia
A. Diagnosis
1. Schizophrenia was originally called dementia praecox. Eugen Bleuler came up with
the term schizophrenia in 1911, which has been preferred ever since.
2. Schizophrenia: A disorder characterized both by deteriorating ability to function in
everyday life paired with at least two of the following symptoms, including at least
one of the first three:
• Delusions: Unjustifiable beliefs, such as “beings from outer space are
controlling my actions.”
• Hallucinations: False sensory experiences, such as hearing voices when alone
• Disorganized speech: rambling or incoherent
• Grossly disorganized behavior
• Weak or absent signs of emotion, speech, and socialization

3. Positive symptoms: Behaviors that are present that should be absent. Positive
symptoms fall into two clusters that do not correlate strongly with each other.
4. Negative symptoms: Behaviors that are absent that should be present, such as
deficits of social interaction and emotional expression.
5. Cognitive symptoms: Limitations of thought and reasoning that are common in
schizophrenia.
6. The main problem is disordered thinking, which results from abnormal interactions
between the cortex and the thalamus and cerebellum. This may lead to the
hallucinations, delusions, and other symptoms.
7. Differential Diagnosis: It is important to rule out other possible diagnoses that
could present like schizophrenia, such as:
a. Substance abuse
b. Brain damage
c. Undetected hearing deficits
d. Huntington’s disease
e. Nutritional abnormalities
8. Demographic Data
a. Schizophrenia occurs in all ethnic groups and is slightly more common in men
than in women; however, it usually develops at an earlier age in men and is
more severe. About 1 percent of people suffer from schizophrenia at any given
time.
b. Mysteries still remain:
i. Link to colon cancer & certain autoimmune diseases.
ii. Characteristic body odor (trans-3-methyl-2-hexenoic acid).
iii. Women having schizophrenic breakdowns & male versus female children
iv. Deficits in pursuit eye movements
B. Genetics
1. Twin Studies
a. For monozygotic schizophrenic twins, there is about a 50 percent concordance
(agreement), and a 15 percent concordance for dizygotic twins.
b. The greater concordance in monozygotic twins does not necessarily mean a
genetic cause, as a pure genetic effect would have a 100 percent concordance.
The greater environmental similarity in monozygotic twins, as compared to
dizyogotic twins, may also influence concordance rates.
c. Dizygotic twins have the same genetic resemblance as siblings but greater
environmental similarity, including prenatal environment.
2. Adopted Children Who Develop Schizophrenia
a. One study found that 12.5 percent of the immediate biological relatives and
none of the adopting relatives had schizophrenia.
b. These results suggest a genetic basis for schizophrenia. There is also the
possibility of a prenatal influence. For example, many women with
schizophrenia drink and smoke during pregnancy.
3. Efforts to Locate a Gene
a. One gene has consistently been linked with schizophrenia. A dozen genes
appear to be more common in people with schizophrenia.

b. DISC1 (disrupted in schizophrenia 1) gene controls the production of dendritic
spines and the generation of new neurons in the hippocampus.
c. Other genes linked to schizophrenia are important for brain development,
transmission of glutamate synapses, and connections between the hippocampus
and the prefrontal cortex.
d. Schizophrenia may result from a combination of genetic and environmental
factors.
C. The Neurodevelopmental Hypothesis: Schizophrenia is caused in large part by
abnormalities to the nervous system during the prenatal or neonatal periods.
1. Prenatal and Neonatal Environment
a. Several factors could have affected the infant’s brain development, including
poor nutrition of the mother during pregnancy, premature birth, low birth
weight, and complications during delivery.
b. If a mother is Rh-negative and her baby is Rh-positive, the baby’s Rh-positive
blood may trigger an immunological rejection by the mother. The result is
hearing deficits, mental retardation, and twice the usual probability of
schizophrenia.
c. Season-of-birth effect: The tendency for people born in winter to have a
slightly greater possibility of developing schizophrenia. Some reason this may
occurs is nutrition during winter, viral infections, fever, and influenza.
d. Childhood infections, like toxoplasma gondii, also infect humans and lead to
memory disorders, hallucinations, and delusions. Because this bacteria only
reproduces in cats, people with schizophrenia are more likely than other people
to have a pet cat in childhood.
2. Mild Brain Abnormalities
a. On average, people with schizophrenia have less than average gray matter and
white matter, and larger than average ventricles—the fluid-filled spaces within
the brain.
b. The strongest deficits are in the left temporal and frontal areas of the cortex.
c. The thalamus is also smaller than normal for people with schizophrenia.
d. The areas with consistent signs of abnormality include some that mature
slowly such as the dorsolateral prefrontal cortex. Most people with
schizophrenia show deficits in memory and attention because of these
deficiencies.
e. Lateralization also differs, with the left hemisphere slightly larger than the
right.
3. Early Development and Later Psychopathology
a. It is currently thought that the early brain damage occurs in areas that are slow
to mature, such as the prefrontal cortex. For this reason, the damage produces
only minor symptoms in childhood, but increasing impairments when the brain
area fully matures.
b. Those who later develop schizophrenia often have other problems in
childhood, like deficits in attention, memory, and impulse control.
D. Treatments
1. Antipsychotic Drugs and Dopamine

a. Chlorpromazine (Thorazine): First drug used successfully for the treatment of
schizophrenia.
b. Antipsychotic drugs (neuroleptic drugs): Drugs used for the treatment of
schizophrenia. These drugs work primarily by blocking dopamine receptors.
i. Phenothiazines: A class of neuroleptic drugs that includes
chlorpromazine.
ii. Butyrophenones: A class of neuroleptic drugs that includes haloperidol
(Haldol).
c. Dopamine hypothesis of schizophrenia: According to this hypothesis,
schizophrenia results from excess activity at certain dopamine synapses. The
primary evidence for this hypothesis is the type of drugs that relieve and
aggravate the symptoms of schizophrenia.
d. Substance-induced psychotic disorder: Disorder characterized by
hallucinations and delusions caused by drugs such as cocaine, amphetamine,
and LSD, which increase the activity of dopamine synapses.
e. Schizophrenic people have about twice as many D2 receptors occupied by
dopamine as normal people.
f. Excess activity of dopamine cannot be the sole cause of schizophrenia. Drugs
that block dopamine receptors do so almost immediately, but their effects on
behavior build up gradually over 2 or 3 weeks.
3. Other Medications
a. Mesolimbocortical system: A set of neurons which project from the midbrain
tegmentum to the limbic system. The mesolimbocortical system is believed to
be the area in which antipsychotics have their beneficial effects.
b. Tardive dyskinesia: A serious side effect of antipsychotics; this disorder is
characterized by tremors and other involuntary movements. Tardive dyskinesia
is caused by the prolonged blockade of dopamine receptors in the basal
ganglia.
c. Second generation (atypical) antipsychotics: Drugs (e.g., clozapine) that
alleviate the symptoms of schizophrenia while seldom, if ever, producing
movement problems. These drugs have less intense effects on dopamine type
D2 receptors, but stronger effects at D4 and serotonin 5-HT2 receptors.
d. Atypical antipsychotics are more effective than typical antipsychotics at
relieving the positive symptoms and, to some extent, the negative symptoms of
schizophrenia, but they do not improve overall quality of life more than the
typical antipsychotic drugs.
3. Role of Glutamate
a. Glutamate hypothesis of schizophrenia: Idea that schizophrenia results from
deficient activity at certain glutamate synapses. Because dopamine inhibits
glutamate activity in many parts of the brain, much of the evidence supporting
the dopamine hypothesis of schizophrenia also supports the glutamate
hypothesis of schizophrenia.
b. Researchers have found that the brains of schizophrenic people release lower
than normal amounts of glutamate in the prefrontal cortex and hippocampus.
Schizophrenics also have fewer glutamate receptors.

c. Phencyclidine (PCP): A drug that blocks NMDA glutamate receptors. PCP
administration produces a type of psychosis more similar to schizophrenia than
drugs like cocaine, as PCP induces both negative and positive symptoms.
Moreover, PCP does not produce psychosis in preadolescents and PCP
produces a much more severe psychosis in people with a history of
schizophrenia.
d. Because increasing glutamate activity in the brain would be extremely risky,
there are no drugs used to treat schizophrenia that directly stimulate glutamate
activity. However, there are some experimental compounds that may someday
be used to treat schizophrenia, such as the amino acid glycine, which enhances
the effects of glutamate at NMDA synapses. Glycine is not an effective
antipsychotic by itself but it increases the effects of other antipsychotic drugs.
IV. Autism Spectrum Disorders
A. Symptoms and Characteristics
1. Autism spectrum disorder includes a range of people with varying degrees of
difficulty, and encompasses what used to be called Asperger’s Syndrome as well as
autism.
2. The primary characteristics are:
a. Deficits in social and emotional exchange
b. Deficits in gestures, facial expressions, and other nonverbal communication
c. Stereotyped behaviors, such as repetitive movements
d. Resistance to a change in routine
e. Unusually weak or strong responses to stimuli, such as indifference to pain or a
panicked reaction to sound
B. Genetics and Other Causes
1. Many genes have been linked to autism, but no one of them is found in a high
percentage of people with autism.
2. Probably most cases result from mutations or microdeletions in any number of
genes, including topoisomerase genes, which regulate the repair and replication of
DNA and the production of certain types of RNA.
3. Scientists can find mutations in genes by comparing the genes to those of the
parents.
4. Prenatal environment can play a role in the development of autism; for this reason,
nutritionists recommend that women planning to become pregnant get adequate
amounts of folic acid (vitamin B9).
C. Treatments
1. No medical treatment can help with the social and communication issues of autism,
but Risperidone (an antipsychotic drug) can help with stereotyped behavior, though
with serious side effects.
2. Behavioral treatments work on the social aspects of autism, focusing on eliciting the child’s attention and reinforcing favorable behaviors.