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FOUNDATIONS OF BEHAVIORAL NEUROSCIENCE
9TH EDITION
Prepared by Grant McLaren, Department of Psychology, Edinboro University of Pennsylvania
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Chapter 15
Schizophrenia, Affective Disorders, and Anxiety
Disorders
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Schizophrenia
Description
Heritability
Pharmacology of Schizophrenia: The Dopamine Hypothesis
Schizophrenia as a Neurological Disorder
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Major Affective Disorders
Description
Heritability
Biological Treatments
The Monoamine Hypothesis
Role of the Frontal Cortex
Role of Neurogenesis
Role of Circadian Rhythms
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Anxiety Disorders
Panic Disorder
Generalized Anxiety Disorder
Social Anxiety Disorder
Obsessive-Compulsive Disorder
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Schizophrenia, Affective Disorders, and Anxiety
Disorders
Learning Objectives
1.
2.
3.
4.
5.
Describe the symptoms of schizophrenia and discuss evidence
concerning its heritability.
Summarize the dopamine hypothesis of schizophrenia and
discuss drugs that alleviate or produce the positive symptoms of
schizophrenia.
Describe evidence that schizophrenia may result from abnormal brain
development.
Describe evidence linking both the positive and negative symptoms to
decreased activity of the prefrontal cortex.
Describe the two major affective disorders, their heritability, and their
physiological treatments.
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Schizophrenia, Affective Disorders, and Anxiety
Disorders
Learning Objectives
6.
Summarize the monoamine hypothesis of depression and review
evidence for brain abnormalities in people with affective disorders.
7.
Explain the role of circadian rhythms in affective disorders: the
effects of REM sleep deprivation and total sleep deprivation and the
symptoms and treatment of seasonal affective disorder.
8.
Describe the symptoms, possible causes, and treatments of panic
disorder, generalized anxiety disorder, and social anxiety disorder.
9.
Describe the symptoms, possible causes, and treatments of
obsessive-compulsive disorder.
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Schizophrenia
Description
Schizophrenia is a serious mental disorder that afflicts
approximately 1 percent of the world’s population.
Its monetary cost to society is enormous; in the United States this
figure exceeds that of the cost of all cancers (Thaker and
Carpenter, 2001).
Schizophrenia is probably the most misused psychological term in
existence.
The word literally means “split mind,” but it does not imply a split
or multiple personality.
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Schizophrenia
Description
schizophrenia
A serious mental disorder characterized by disordered
thoughts, delusions, hallucinations, and often bizarre
behaviors.
positive symptom
A symptom of schizophrenia evident by its presence:
delusions, hallucinations, or thought disorders.
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Schizophrenia
Description
thought disorder
Disorganized, irrational thinking.
delusion
A belief that is clearly in contradiction to reality.
hallucination
Perception of a nonexistent object or event.
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Schizophrenia
Description
negative symptom
A symptom of schizophrenia characterized by the absence
of behaviors that are normally present: social withdrawal,
lack of affect, and reduced motivation.
cognitive symptom
A symptom of schizophrenia characterized by cognitive
difficulties, such as deficits in learning and memory, poor
abstract thinking, and poor problem solving.
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Schizophrenia
Description
The symptoms of schizophrenia typically appear gradually and
insidiously, over a period of three to five years.
Negative symptoms are the first to emerge, followed by cognitive
symptoms.
The positive symptoms follow several years later.
As we will see later, this progression of symptoms provides some
hints about the nature of the brain abnormalities that are
responsible for them.
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Schizophrenia
Heritability
One of the strongest pieces of evidence that schizophrenia is a
biological disorder is that it appears to be heritable.
Both adoption studies (Kety et al., 1968, 1994) and twin studies
(Gottesman and Shields, 1982; Tsuang, Gilbertson, and Faraone,
1991) indicate that schizophrenia is a heritable trait.
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Schizophrenia
Heritability
So far, researchers have not yet located a single “schizophrenia
gene,” although researchers have found many candidate genes
that appear to increase the likelihood of this disease.
A review by Crow (2007) notes that evidence for linkage to
susceptibility for schizophrenia has been reported for 21 of the 23
pairs of chromosomes, but many of the findings have not been
replicated.
So far, no single gene has been shown to cause schizophrenia.
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Schizophrenia
Pharmacology of Schizophrenia: The Dopamine Hypothesis
Pharmacological evidence suggests that the positive symptoms of
schizophrenia are caused by abnormalities in DA neurons.
The dopamine hypothesis suggests that the positive symptoms of
schizophrenia are caused by overactivity of DA synapses.
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Schizophrenia
Pharmacology of Schizophrenia: The Dopamine Hypothesis
Since the discovery of chlorpromazine, many other drugs have
been developed that relieve the positive symptoms of
schizophrenia.
These drugs were found to have one property in common: They
block dopamine receptors (Creese, Burt, and Snyder, 1976;
Strange, 2008).
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Schizophrenia
Pharmacology of Schizophrenia: The Dopamine Hypothesis
Most researchers believe that the mesolimbic pathway, which
begins in the ventral tegmental area and ends in the nucleus
accumbens and amygdala, is likely to be involved in the
symptoms of schizophrenia.
As we saw in Chapter 12, the activity of dopaminergic synapses in
the mesolimbic system appears to be a vital link in the process of
reinforcement.
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Schizophrenia
Pharmacology of Schizophrenia: The Dopamine Hypothesis
The positive symptoms of schizophrenia also include disordered
thinking and unpleasant, often terrifying delusions.
The disordered thinking may be caused by disorganized
attentional processes; the indiscriminate activity of the
dopaminergic synapses in the nucleus accumbens makes it
difficult for the patients to follow an orderly, rational thought
sequence.
Fibiger (1991) suggests that paranoid delusions may be caused
by increased activity of the dopaminergic input to the amygdala.
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Schizophrenia
Pharmacology of Schizophrenia: The Dopamine Hypothesis
Recent years have seen the development of the atypical
antipsychotic medications, which reduce both the positive
symptoms and negative symptoms of schizophrenia—even those
of many patients who were not significantly helped by the older
antipsychotic drugs.
Clozapine, the first of the atypical antipsychotic medications, has
been joined by several others, including risperidone, olanzapine,
ziprasidone, and aripiprazole.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Compared to the positive symptoms, the negative and cognitive
symptoms of schizophrenia are very different.
Whereas the positive symptoms are unique to schizophrenia, the
negative and cognitive symptoms are similar to those produced by
brain damage caused by several different means.
Many pieces of evidence suggest that these symptoms of
schizophrenia are indeed a result of brain abnormalities in the
prefrontal cortex.
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Schizophrenia
Schizophrenia as a Neurological Disorder
There appear to be three possibilities: Predisposing factors
(genetic, environmental, or both) give rise to:
1) abnormalities in both DA transmission and in the
prefrontal cortex
2) abnormalities in DA transmission that cause
abnormalities in the prefrontal cortex
3) abnormalities in the prefrontal cortex that cause
abnormalities in DA transmission.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Evidence for Brain Abnormalities in Schizophrenia
Although schizophrenia has traditionally been labeled a
psychiatric disorder, most patients with schizophrenia exhibit
neurological symptoms that suggest the presence of brain
damage—in particular, poor control of eye movements and
unusual facial expressions (Stevens, 1982).
In addition, many studies have found evidence of loss of brain
tissue in CT and MRI scans of schizophrenic patients.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Evidence for Brain Abnormalities in Schizophrenia
In one of the earliest studies, Weinberger and Wyatt (1982)
obtained CT scans of eighty chronic schizophrenics and sixty-six
normal controls of the same mean age (twenty-nine years).
They found that the relative size of the lateral ventricles of the
schizophrenic patients was more than twice as great as that of the
normal control subjects. (See Figure 15.1.)
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Schizophrenia
Schizophrenia as a Neurological Disorder
Evidence for Brain Abnormalities in Schizophrenia
The most likely cause of the enlarged ventricles is loss of brain
tissue; thus, the CT scans provide evidence that chronic
schizophrenia is associated with brain abnormalities.
In fact, Hulshoff-Pol et al. (2002) found that although everyone
loses some cerebral gray matter as they age, the rate of tissue
loss is greater in schizophrenic patients.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Possible Causes of Brain Abnormalities
Why do fewer than half the children of parents with chronic
schizophrenia become schizophrenic?
Perhaps what is inherited is a defect that renders people
susceptible to some environmental factors that adversely affect
brain development or cause brain damage later in life.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Epidemiological Studies
epidemiology
The study of the distribution and causes of diseases in
populations.
Evidence from these studies indicates that the incidence of
schizophrenia is related to several environmental factors:, season
of birth, viral epidemics, population density, and substance abuse
(Brown and Derkits, 2010; King, St-Hilaire, and Heidkamp, 2010).
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Schizophrenia
Schizophrenia as a Neurological Disorder
Epidemiological Studies
seasonality effect
The increased incidence of schizophrenia in people born
during late winter and early spring.
Kendell and Adams (1991) studied the month of birth of over
13,000 schizophrenic patients born in Scotland between 1914 and
1960.
They found that disproportionately more patients were born in
February, March, April, and May. (See Figure 15.2.)
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Schizophrenia
Schizophrenia as a Neurological Disorder
Epidemiological Studies
In fact, Kendell and Adams (1991) found that the relative number
of schizophrenic births in late winter and early spring was
especially high if the temperature was lower than normal during
the previous autumn—a condition that keeps people indoors and
favors the transmission of viral illnesses.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Epidemiological Studies
Similarly, Eaton, Mortensen, and Frydenberg (2000) reported that
schizophrenia is approximately three times higher in people who
live in the middle of large cities than in those who live in rural
areas, presumably because the transmission of infectious
illnesses is facilitated by increased population density.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Epidemiological Studies
Although cold weather and crowding may contribute to the
seasonality effect by increasing the likelihood of infectious illness,
another variable may also play a role: a vitamin D deficiency.
Dealberto (2007) notes that Northern European researchers have
observed a threefold increase in the incidence of schizophrenia in
immigrants and the children of immigrants—especially in darkskinned people.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Epidemiological Studies
A final environmental risk factor for development of schizophrenia
is maternal substance abuse—particularly smoking. Zammit et al.
(2009) studied the effects of maternal use of tobacco, cannabis or
alcohol during pregnancy and found that tobacco use was
associated with increased risk.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Epidemiological Studies
Even paternal tobacco use increased this risk, which suggest that
second-hand smoke was sufficient to adversely affect fetal
development.
Excessive alcohol intake increased the risk of schizophrenia only
if the mother drank more than 210 ml of pure alcohol per week.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Evidence for Abnormal Brain Development
Both behavioral and anatomical evidence indicates that abnormal
prenatal development is associated with schizophrenia.
The results of these studies are consistent with the hypothesis
that although the symptoms of schizophrenia are not normally
seen in childhood, the early brain development of children who
later become schizophrenic is not entirely normal.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Evidence for Abnormal Brain Development
The concordance rate of monozygotic twins for schizophrenia is
less than 100 percent.
However, some investigators have pointed out that the prenatal
environment of monozygotic twins is not identical.
In fact, there are two types of monozygotic twins: monochorionic
and dichorionic.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Evidence for Abnormal Brain Development
The prenatal environments of monochorionic twins, who share a
single placenta, are more similar than those of dichorionic twins.
Thus, we might expect that the concordance rates for
schizophrenia of monochorionic monozygotic twins should be
higher than those of dichorionic monozygotic twins.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Evidence for Abnormal Brain Development
In fact, they are.
Davis, Phelps, and Bracha (1995) found that the concordance rate
for schizophrenia was 10.7 percent in the dichorionic twins and 60
percent in the monochorionic twins.
These results provide strong evidence for an interaction between
heredity and environment during prenatal development.
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Schizophrenia
Schizophrenia as a Neurological Disorder
Evidence for Abnormal Brain Development
Although studies have found that people who develop
schizophrenia show some abnormalities even during childhood,
the symptoms of schizophrenia itself rarely begin before late
adolescence or early adulthood.
If schizophrenia does begin during childhood, the symptoms are
likely to be more severe.
Figure 15.4 shows a graph of the ages of first signs of mental
disorder in males and females diagnosed with schizophrenia.
(See Figure 15.4.)
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Schizophrenia
Relationship between Positive and Negative Symptoms: Role of
the Prefrontal Cortex
As we saw, schizophrenia has positive, negative, and cognitive
symptoms.
The positive symptoms may be caused by hyperactivity of
dopaminergic synapses, and the negative and cognitive
symptoms may be caused by developmental or degenerative
changes in the brain.
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Schizophrenia
Relationship between Positive and Negative Symptoms: Role of
the Prefrontal Cortex
Weinberger (1988) first suggested that the negative symptoms of
schizophrenia are caused primarily by hypofrontality, decreased
activity of the frontal lobes—in particular, of the dorsolateral
prefrontal cortex (dlPFC).
In fact, schizophrenic patients do poorly on neuropsychological
tests that are sensitive to prefrontal damage.
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Schizophrenia
Relationship between Positive and Negative Symptoms: Role of
the Prefrontal Cortex
hypofrontality
Decreased activity of the prefrontal cortex; believed to
be responsible for the negative symptoms of
schizophrenia.
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Schizophrenia
Relationship between Positive and Negative Symptoms: Role of
the Prefrontal Cortex
The atypical antipsychotic drug clozapine alleviates the positive,
negative, and cognitive symptoms of schizophrenia.
In a study with monkeys, Youngren et al. (1999) found that
injections of clozapine, which cause an increase in the release of
dopamine in the prefrontal cortex, also causes a decrease in the
release of dopamine by the mesolimbic system, which apparently
reduces the negative and cognitive symptoms.
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Schizophrenia
Relationship between Positive and Negative Symptoms: Role of
the Prefrontal Cortex
A mutation of the DISC1 gene is a known genetic cause of
schizophrenia.
Niwa et al. (2010) infused a small interfering RNA (siRNA) that
targeted the DISC1 gene into progenitor cells of the ventricular
zone of fetal mice.
Abnormalities also began appearing in the mesocortical
dopaminergic system that projects to the prefrontal cortex, which
resulted in a lower level of dopamine in this region.
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Schizophrenia
Relationship between Positive and Negative Symptoms: Role of
the Prefrontal Cortex
While these changes were occurring, behavioral abnormalities
resembling those of schizophrenia began to emerge.
These findings suggest that abnormalities in the pyramidal
neurons of the prefrontal cortex constitute the primary cause of
the process that leads to schizophrenia. (See Figure 15.6.)
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Schizophrenia
Relationship between Positive and Negative Symptoms: Role of
the Prefrontal Cortex
Aripiprazole acts as a partial agonist at dopamine receptors.
partial agonist
A drug that has a very high affinity for a particular
receptor but activates that receptor less than the
normal ligand does; serves as an agonist in regions of
low concentration of the normal ligand and as an
antagonist in regions of high concentrations.
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Major Affective Disorders
major affective disorder
A serious mood disorder; includes unipolar depression
and bipolar disorder.
Affect, as a noun, refers to feelings or emotions.
Just as the primary symptom of schizophrenia is disordered
thoughts, the major affective disorders (also called mood
disorders) are characterized by disordered feelings.
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Major Affective Disorders
Description
Depression has a prevalence of approximately 3 percent in men
and 7 percent in women, which makes it the 4th leading cause of
disability (Kessler et al., 2003).
There are two principal types of major affective disorders:
1. Bipolar Disorder
2. Major Depressive Disorder
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Major Affective Disorders
Description
bipolar disorder
A serious mood disorder characterized by cyclical
periods of mania and depression.
major depressive disorder (MDD)
A serious mood disorder that consists of unremitting
depression or periods of depression that do not
alternate with periods of mania.
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Major Affective Disorders
Description
Severely depressed people usually feel unworthy and have strong
feelings of guilt.
The affective disorders are dangerous; a person who suffers from
a major affective disorder runs a considerable risk of death by
suicide.
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Major Affective Disorders
Description
Depressed people have very little energy, and they move and talk
slowly, sometimes becoming almost torpid.
At other times, they may pace around restlessly and aimlessly.
They may cry a lot.
They are unable to experience pleasure and lose their appetite for
food and sex.
Their sleep is disturbed; they usually have difficulty falling asleep
and awaken early and find it difficult to get to sleep again.
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Major Affective Disorders
Description
Episodes of mania are characterized by a sense of euphoria that
does not seem to be justified by circumstances.
The diagnosis of mania is partly a matter of degree; one would not
call exuberance and a zest for life pathological.
People with mania usually exhibit nonstop speech and motor
activity.
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Major Affective Disorders
Description
They flit from topic to topic and often have delusions, but they lack
the severe disorganization that is seen in schizophrenia.
They are usually full of their own importance and often become
angry or defensive if they are contradicted.
Frequently, they go for long periods without sleep, working
furiously on projects that are often unrealistic.
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Major Affective Disorders
Heritability
Evidence indicates that a tendency to develop an affective
disorder is a heritable characteristic.
Gershon et al. (1976) found that if one member of a set of
monozygotic twins was afflicted with an affective disorder, the
likelihood that the other twin was similarly afflicted was 69
percent.
In contrast, the concordance rate for dizygotic twins was only 13
percent.
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Major Affective Disorders
Heritability
Genetic studies have found evidence that genes on several
chromosomes may be implicated in the development of the
affective disorders, but the findings of most of the earlier linkage
studies have not been replicated (Hamet and Tremblay, 2005).
A review of genome-wide association studies (Terracciano et al.,
2010) found that the RORA gene, involved in control of circadian
rhythms, had the strongest association with the occurrence of
major depressive disorder.
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Major Affective Disorders
Heritability
Evidence suggested that another gene, GRM8, which codes for
the production of a metabolic glutamate receptor, may also be
involved. (McGrath et al., 2009) found that RORB, another clock
gene, was associated with rapid cycling bipolar disorder seen in
children.
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Major Affective Disorders
Season of Birth
A seasonality effect—but a different one—is seen in the incidence
of major depression.
Döme et al. (2010) examined the season of birth of 80,000 people
who committed suicide in Hungary in the 1930s, early-to-mid
1940s, and 1969. (Hungary has one of the highest rates of suicide
in the world.)
The incidence of suicide was significantly higher in summer, with a
peak in July. (See Figure 15.8.) So far, there is no explanation for
this phenomenon.
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Major Affective Disorders
Biological Treatments
There are several established and experimental biological
treatments for major depressive disorder: monoamine oxidase
(MAO) inhibitors, drugs that inhibit the reuptake of norepinephrine
or serotonin, electroconvulsive therapy (ECT), transcranial
magnetic stimulation, deep brain stimulation, vagus nerve
stimulation, bright-light therapy (phototherapy), and sleep
deprivation.
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Major Affective Disorders
Biological Treatments
The fact that these disorders often respond to biological treatment
provides additional evidence that they have a physiological basis.
Furthermore, the fact that lithium is effective in treating bipolar
affective disorder but not major depressive disorder suggests that
there is a fundamental difference between these two illnesses.
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Major Affective Disorders
Biological Treatments
tricyclic antidepressant
A class of drugs used to treat depression; inhibits the
reuptake of norepinephrine and serotonin but also
affects other neurotransmitters; named for the molecular
structure.
specific serotonin reuptake inhibitor (SSRI)
An antidepressant drug that specifically inhibits the
reuptake of serotonin without affecting the reuptake of
other neurotransmitters.
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Major Affective Disorders
Biological Treatments
serotonin and norepinephrine reuptake inhibitor (SNRI)
An antidepressant drug that specifically inhibits the
reuptake of norepinephrine and serotonin without affecting
the reuptake of other neurotransmitters.
electroconvulsive therapy (ECT)
A brief electrical shock, applied to the head, that results in
an electrical seizure; used therapeutically to alleviate
severe depression.
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Major Affective Disorders
Biological Treatments
Even when depressed patients respond to treatment with
antidepressant drugs, they do not do so immediately;
improvement in symptoms is not usually seen before two to three
weeks of drug treatment.
In contrast, the effects of ECT are more rapid.
A few seizures induced by ECT can often snap a person out of a
deep depression within a few days.
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Major Affective Disorders
Biological Treatments
Remission of symptoms is greater than 50%, but relapse is a
common problem (Holtzheimer and Mayberg, 2011.
Although prolonged and excessive use of ECT causes brain
damage, resulting in long-lasting impairments in memory (Squire,
1974), the judicious use of ECT during the interim period before
antidepressant drugs become effective has undoubtedly saved
the lives of some suicidal patients.
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Major Affective Disorders
Biological Treatments
Preliminary research also suggests that deep brain stimulation
(DBS) may also be a useful therapy for treatment-resistant
depression (Mayberg et al., 2005; Lozano et al., 2008).
Mayberg and her colleagues implanted electrodes just below the
subgenual anterior cingulate cortex (subgenual ACC), a region of
the medial prefrontal cortex.
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Major Affective Disorders
Biological Treatments
subgenual anterior cingulate cortex (subgenual ACC)
A region of the medial prefrontal cortex located below the
“knee” at the front of the corpus callosum; plays a role in
the symptoms of depression.
Response to the stimulation began soon, and it increased with
time.
One month after surgery, 35 percent of the patients showed an
improvement in symptoms, and 10 percent showed a complete
remission. Six months after surgery, 60 percent showed
improvement, and 35 percent showed remission.
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Major Affective Disorders
Biological Treatments
Deep brain stimulation has also been directed toward the nucleus
accumbens.
The release of dopamine in this region plays a critical role in
reinforcement and the response to pleasurable stimuli.
Bewernick et al. (2010) found that DBS of the nucleus accumbens
did indeed reduce the symptoms of depression in 50 percent of
treatment-resistant patients who had previously shown no
response to pharmacological treatment, psychotherapy, or ECT.
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Major Affective Disorders
Biological Treatments
The therapeutic effect of lithium, the drug used to treat bipolar
affective disorders, is very rapid.
lithium
A chemical element; lithium carbonate is used to treat
bipolar disorder.
This drug, which is administered in the form of lithium carbonate,
is most effective in treating the manic phase of a bipolar affective
disorder; once the mania is eliminated, depression usually does
not follow.
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Major Affective Disorders
The Monoamine Hypothesis
Depression is caused by insufficient activity of monoaminergic
neurons.
Because the symptoms of depression are not relieved by potent
dopamine agonists such as amphetamine or cocaine, most
investigators have focused their research efforts on the other two
monoamines: norepinephrine and serotonin.
monoamine hypothesis
A hypothesis that states that depression is caused by a
low level of activity of one or more monoaminergic
synapses.
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Major Affective Disorders
The Monoamine Hypothesis
The monoamine hypothesis of depression was suggest by the fact
that monoamine antagonists can produce the symptoms of
depression and monoamine agonists can reduce them.
tryptophan depletion procedure
A procedure involving a low-tryptophan diet and a
tryptophan-free amino acid “cocktail” that lowers brain
tryptophan and consequently decreases the synthesis
of 5-HT.
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Major Affective Disorders
The Monoamine Hypothesis
Although SSRIs and SNRIs change the increase the level of 5-HT
or norepinephrine in the brain very rapidly, the drugs do not
relieve the symptoms of depression until they have been taken for
several weeks.
This fact suggests that something other than a simple increase in
monoaminergic activity in responsible for the normalization of
mood.
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Major Affective Disorders
The Monoamine Hypothesis
Many investigators believe that the increased extracellular levels
of monoamines produced by administration of antidepressant
drugs begin a chain of events that eventually produce changes in
the brain that are ultimately responsible for antidepressant effect.
The nature of this chain of events is still unknown.
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Major Affective Disorders
Role of the Frontal Cortex
Figure 15.10 shows the results of functional imaging scans of the
medial frontal region of depressed patients who were successfully
treated with a variety of treatments.
Increases in activity after successful treatment are shown in red;
decreases are shown in blue.
Successful treatment led to decreased activity in the subgenual
ACC. (See Figure 15.10.)
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Major Affective Disorders
Role of the Frontal Cortex
The successful treatment of the symptoms of depression, which
decreases the activity of the subgenual ACC, may result in
decreased activity of the amygdala through direct connections
between these two structures and through indirect connections via
the prefrontal cortex.
The precise role of the subgenual ACC will be elucidated only
through further research.
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Major Affective Disorders
Role of the Neurogenesis
Neurogenesis can take place in the dentate gyrus—a region of the
hippocampal formation—in the adult brain.
Several studies with laboratory animals have shown that stressful
experiences that produce the symptoms of depression suppress
hippocampal neurogenesis, and the administration of
antidepressant treatments, including MAO inhibitors, tricyclic
antidepressants, SSRIs, ECT, and lithium, increases
neurogenesis.
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Major Affective Disorders
Role of the Neurogenesis
There is currently no way to measure the rate of neurogenesis in
the human brain.
So far, all the evidence about human neurogenesis has been by
extrapolation from studies with laboratory animals.
Histological procedures verified that increased neurogenesis in
the mouse brain correlated with the increased blood volume,
which supports the suggestion that exercise induces
neurogenesis in the human brain, as well. (See Figure 15.11.)
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Major Affective Disorders
Role of Circadian Rhythms
One of the most prominent symptoms of depression is disordered
sleep.
The sleep of people with depression tends to be shallow; slowwave delta sleep (stages 3 and 4) is reduced, and stage 1 is
increased.
Sleep is fragmented; people tend to awaken frequently, especially
toward the morning.
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Major Affective Disorders
Role of Circadian Rhythms
In addition, REM sleep occurs earlier, the first half of the night
contains a higher proportion of REM periods, and REM sleep
contains an increased number of rapid eye movements (Kupfer,
1976; Vogel et al., 1980). (See Figure 15.12.)
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Major Affective Disorders
Role of Circadian Rhythms
REM Sleep Deprivation
One of the most effective antidepressant treatments is sleep
deprivation, either total or selective.
Selective deprivation of REM sleep, accomplished by monitoring
people’s EEG and awakening them whenever they show signs of
REM sleep, alleviates depression (Vogel et al., 1975, 1990).
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Major Affective Disorders
Role of Circadian Rhythms
REM Sleep Deprivation
The therapeutic effect, like that of the antidepressant medications,
occurs slowly, over the course of several weeks.
Some patients show long-term improvement even after the
deprivation is discontinued; thus, it is a practical as well as an
effective treatment.
In addition, regardless of their specific pharmacological effects,
other treatments for depression suppress REM sleep, delaying its
onset and decreasing its duration
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Major Affective Disorders
Role of Circadian Rhythms
REM Sleep Deprivation
These results suggest that an important effect of successful
antidepressant treatment may be to suppress REM sleep, and the
changes in mood may be a result of this suppression.
However, at least one antidepressant drug has been shown in a
double-blind, placebo-controlled study not to suppress REM sleep
(Mayers and Baldwin, 2005).
Thus, suppression of REM sleep cannot be the only way in which
antidepressant drugs work.
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Major Affective Disorders
Role of Circadian Rhythms
Slow-Wave Sleep Deprivation
Another form of selective sleep deprivation, slow-wave sleep
deprivation (SWS deprivation) effectively reduces depressive
symptoms in some patients.
Whenever slow waves appeared in a person’s EEG, the
investigators presented sounds that suppressed the slow waves
without waking the person up.
The results were promising: self-rated symptoms of depression
decreased in most of the patients. (See Figure 15.13.)
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Major Affective Disorders
Role of Circadian Rhythms
Total Sleep Deprivation
Total sleep deprivation also has an antidepressant effect. Unlike
specific deprivation of REM sleep, which takes several weeks to
reduce depression, total sleep deprivation produces immediate
effects (Wu and Bunney, 1990).
Typically, the depression is lifted by the sleep deprivation but
returns the next day, after a normal night’s sleep.
Wu and Bunney suggest that during sleep, the brain produces a
chemical that has a depressogenic effect in susceptible people.
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Major Affective Disorders
Role of Circadian Rhythms
Role of Zeitgebers
Another phenomenon relates depression to sleep and waking—or,
more specifically, to the mechanisms that are responsible for
circadian rhythms.
Some people become depressed during the winter season, when
days are short and nights are long.
seasonal affective disorder
A mood disorder characterized by depression, lethargy,
sleep disturbances, and craving for carbohydrates
during the winter season when days are short.
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Major Affective Disorders
Role of Circadian Rhythms
Role of Zeitgebers
Seasonal affective disorder, like MDD and bipolar disorder,
appears to have a genetic basis. In a study of 6439 adult twins,
Madden et al. (1996) found that seasonal affective disorder ran in
families, and they estimated that at least 29 percent of the
variance in seasonal mood disorders could be attributed to
genetic factors.
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Major Affective Disorders
Role of Circadian Rhythms
Role of Zeitgebers
Seasonal affective disorder can be treated by phototherapy:
exposing people to bright light for several hours a day (Rosenthal
et al., 1985; Stinson and Thompson, 1990).
phototherapy
Treatment of seasonal affective disorder by daily
exposure to bright light.
Light serves as a zeitgeber; that is, it synchronizes the activity of
the biological clock to the day–night cycle.
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Anxiety Disorders
anxiety disorder
A psychological disorder characterized by tension,
overactivity of the autonomic nervous system, expectation
of an impending disaster, and continuous vigilance for
danger.
panic disorder
A disorder characterized by episodic periods of
symptoms such as shortness of breath, irregularities in
heartbeat, and other autonomic symptoms,
accompanied by intense fear.
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Anxiety Disorders
anticipatory anxiety
A fear of having a panic attack; may lead to the
development of agoraphobia.
agoraphobia
A fear of being away from home or other protected
places.
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Anxiety Disorders
generalized anxiety disorder
A disorder characterized by excessive anxiety and
worry serious enough to cause disruption of their lives.
social anxiety disorder
A disorder characterized by excessive fear of being
exposed to the scrutiny of other people that leads to
avoidance of social situations in which the person is
called on to perform.
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Anxiety Disorders
Possible Causes
Family studies and twin studies indicate that panic disorder,
generalized anxiety disorder, and social anxiety disorder all have
a hereditary component (Hettema, Neale, and Kendler, 2001;
Merikangas and Low, 2005).
Genetic investigations indicate that variations in the gene that
encodes production the BDNF protein may play a role in anxiety
disorders.
BDNF (brain-derived neurotrophic factor) regulates neuronal
survival and differentiation during development, plays a role in
long-term potentiation and memory, and is associated with anxiety
and depression (Yu et al., 2009).
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Anxiety Disorders
Possible Causes
Functional imaging studies suggest that the amygdala and the
cingulate, prefrontal, and insular cortices are involved in anxiety
disorders.
Monk et al. (2008) found that adolescents with generalized anxiety
disorder showed increased activation of the amygdala and
decreased activation of the ventrolateral prefrontal cortex while
looking at angry faces.
Stein et al. (2007) found that college students with a high level of
anxiety showed increased activation of the amygdala and the
insular cortex, both of which correlated positively with students’
anxiety measures.
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Anxiety Disorders
Treatment
Anxiety disorders are sometimes treated with benzodiazepines.
Increased activity of the amygdala is a common feature of the
anxiety disorders.
The amygdala contains a high concentration of GABAA receptors,
which are the target of the benzodiazepines.
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Anxiety Disorders
Treatment
Benzodiazepines are often used for emergency medical treatment
for anxiety disorders because the therapeutic effects of these
drugs have a rapid onset.
However, they are less satisfactory for long-term treatment.
They cause sedation, they induce tolerance and withdrawal
symptoms, and they have a potential for abuse.
For these reasons, researchers have been seeking other drugs to
treat anxiety disorders.
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Anxiety Disorders
Treatment
Much evidence suggests that serotonin plays a role in anxiety
disorders too.
Even though the symptoms of the anxiety disorders discussed in
this subsection are very different from those of obsessivecompulsive.
Specific serotonin reuptake inhibitors, which serve as potent
serotonin agonists (such as fluoxetine), have become the first-line
medications for treating all of these disorders—preferably in
combination with cognitive behavior therapy.
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Anxiety Disorders
Obsessive-Compulsive Disorder
The incidence of obsessive-compulsive disorder is 1–2 percent.
Females are slightly more likely than males to have this diagnosis.
OCD most commonly begins in young adulthood (Robbins et al.,
1984).
People with severe symptoms of this disorder are unlikely to
marry, perhaps because of the common obsessional fear of dirt
and contamination or because of the shame associated with the
rituals they are compelled to perform, which causes them to avoid
social contacts.
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Anxiety Disorders
Obsessive-Compulsive Disorder
obsessive-compulsive disorder (OCD)
A mental disorder characterized by obsessions and
compulsions.
obsession
An unwanted thought or idea with which a person is
preoccupied.
compulsion
The feeling that one is obliged to perform a behavior, even
if one prefers not to do so.
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Anxiety Disorders
Obsessive-Compulsive Disorder
Possible Causes
Evidence suggests that obsessive-compulsive disorder has a
genetic origin.
Several studies have found a greater concordance for obsessions
and compulsions in monozygotic twins than in dizygotic twins
(Hettema, Neale, and Kendler, 2001)
At least two studies suggest that chromosome 9 contains a region
associated with OCD (Hanna et al., 2002; Willour et al., 2004).
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Anxiety Disorders
Obsessive-Compulsive Disorder
Possible Causes
Not all cases of OCD have a genetic origin; the disorder
sometimes occurs after brain damage caused by various means,
such as birth trauma, encephalitis, and head trauma (Hollander et
al., 1990; Berthier et al., 1996).
In particular, the symptoms of OCD appear to be associated with
damage to or dysfunction of the basal ganglia, cingulate gyrus,
and prefrontal cortex (Giedd et al., 1995; Robinson et al., 1995).
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Anxiety Disorders
Obsessive-Compulsive Disorder
Possible Causes
Several functional imaging studies have found evidence of
increased activity in the frontal lobes and caudate nucleus in
patients with OCD.
A review by Whiteside, Port, and Abramowitz (2004) found that
functional imaging studies consistently found increased activity of
the caudate nucleus and the prefrontal cortex.
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Anxiety Disorders
Obsessive-Compulsive Disorder
Treatment
The prefrontal cortex and the cingulate cortex are involved in
emotional reactions, so it is not surprising to learn that they might
be implicated in OCD.
In fact, some patients with severe OCD have been successfully
treated with cingulotomy.
cingulotomy
The surgical destruction of the cingulum bundle, which
connects the prefrontal cortex with the limbic system; helps
to reduce intense anxiety and the symptoms of obsessivecompulsive disorder.
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