Consciousness, the Brain, and Behavior
of schizophrenia include hallucinations, especially “hearing”
voices, and delusions, such as the belief that one has been
chosen for a special mission or is being persecuted by oth-
ers. Schizophrenics become withdrawn, are emotionally unre-
sponsive, and experience inappropriate moods. They may also
experience abnormal motor behavior, which can include total
The symptoms vary from person
to person.
The causes of schizophrenia remain unclear. Recent stud-
ies suggest that the disease refl ects a developmental disorder
in which neurons migrate or mature abnormally during brain
formation. The abnormality may be due to a genetic predis-
position or multiple environmental factors such as viral infec-
tions and malnutrition during fetal life or early childhood. The
brain abnormalities involve diverse neural circuits and neu-
rotransmitter systems that regulate basic cognitive processes.
A widely accepted explanation for schizophrenia suggests that
certain dopamine pathways are overactive. This hypothesis
is supported by the fact that amphetamine-like drugs, which
enhance dopamine signaling, make the symptoms worse, and
by the fact that the most therapeutically benefi cial drugs used
in treating schizophrenia block dopamine receptors.
Schizophrenia affects approximately one in every 100
people and typically appears in the late teens or early twenties
just as brain development nears completion. Currently there
is no prevention or cure for the disease, although drugs can
often control the symptoms. In a small number of cases, there
has been complete recovery.
The Mood Disorders: Depressions
and Bipolar Disorders
The term
refers to a pervasive and sustained inner emo-
tion that affects a person’s perception of the world. In addi-
tion to being part of the conscious experience of the person,
others can observe it. In healthy people, moods can be nor-
mal, elated, or depressed, and people generally feel that they
have some degree of control over their moods. That sense of
control is lost, however, in the
mood disorders,
which include
depressive disorders and bipolar disorders. Along with schizo-
phrenia, the mood disorders represent the major psychiatric
illnesses today.
In the
depressive disorders
the promi-
nent features are a pervasive sadness; a loss of energy, inter-
est, or pleasure; anxiety; irritability; disturbed sleep; and
thoughts of death or suicide. Depression can occur on its
own, independent of any other illness, or it can arise second-
ary to other medical disorders. It is associated with decreased
neuronal activity and metabolism in the anterior part of the
limbic system and nearby prefrontal cortex. These same brain
regions show abnormalities, albeit inconsistent ones, in bipo-
lar disorders.
The term
bipolar disorders
describes swings between
mania and depression. Episodes of
are characterized by
an abnormally and persistently elated mood, sometimes with
euphoria (that is, an exaggerated sense of well-being), racing
thoughts, excessive energy, overconfi
dence, and irritability.
Although the major biogenic amine neurotransmitters
(norepinephrine, dopamine, and serotonin) and acetylcholine
have all been implicated, the causes of the mood disorders are
Current treatment of the mood disorders emphasizes
drugs and psychotherapy. The classical anti-depressant drugs
are of three types. The
tricyclic antidepressant drugs
as Elavil
, Norpramin
, and Sinequan
interfere with sero-
tonin and/or norepinephrine reuptake by presynaptic end-
ings. The
monoamine oxidase inhibitors
interfere with the
enzyme responsible for the breakdown of these same two
neurotransmitters. A third class of antidepressant drugs, the
c reuptake inhibitors
are the most
widely used antidepressant drugs and include Prozac
, Paxil
and Zoloft
. As their name—SSRI—suggests, these drugs
selectively inhibit serotonin reuptake by presynaptic terminals.
In all three classes, the result is an increased concentration of
serotonin and (except for the third class) norepinephrine in
the extracellular fl uid at synapses.
The biochemical effects of antidepressant medications
occur immediately but the benefi cial antidepressant effects
appear only after several weeks of treatment. Thus, the known
biochemical effect must be only an early step in a complex
sequence that leads to a therapeutic effect of these drugs.
Consistent with the long latency of the antidepressant effect
is the recent evidence that the ultimate mechanism of these
drugs may involve the growth of new neurons in the hippo-
campus. Chronic stress is a known trigger of depression in
some people, and it has also been shown to inhibit neurogene-
sis in animals. In addition, careful measurements of the hippo-
campus in chronically depressed patients show that it tends to
be smaller than in matched, nondepressed individuals. Finally,
while antidepressant drugs normally have measurable effects
on behavior in animal models of depression, it was recently
shown that those effects disappear completely when steps are
taken to prevent neurogenesis.
A major drug used in treating patients with bipolar dis-
order is the chemical element lithium, sometimes given in
combination with anticonvulsant drugs. It is highly specifi c,
normalizing both the manic and depressing moods and
slowing down thinking and motor behavior without causing
sedation. In addition, it decreases the severity of the swings
between mania and depression that occur in the bipolar disor-
ders. In some cases, lithium is even effective in depression not
associated with mania. Lithium may interfere with the forma-
tion of signaling molecules of the inositol phosphate family,
thereby decreasing the postsynaptic neurons’ response to neu-
rotransmitters that utilize this signal transduction pathway
(Chapter 5).
Psychotherapy of various kinds can also be helpful in
the treatment of depression. An alternative treatment when
drug therapy and psychotherapy are not effective is
convulsive therapy
As the name suggests, pulses of
electric current are used to activate a large number of neurons
in the brain simultaneously, thereby inducing a convulsion,
or seizure. The patient is under anesthesia and prepared with
a muscle relaxant to minimize the effects of the convulsion
on the musculoskeletal system. A series of ECT treatments
alters neurotransmitter function by causing changes in the
sensitivity of certain serotonin and adrenergic postsynaptic
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