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Psychopathology: Biological
Basis of Behavioral
Disorders
16 Psychopathology: Biological Basis of Behavioral Disorders
The Toll of Psychiatric Disorders Is Huge
Schizophrenia is the major neurobiological
challenge in psychiatry.
Mood disorders are a major psychiatric
category.
16 The Toll of Psychiatric Disorders Is Huge
Epidemiology studies patterns of disease in
a population.
About one third of the U.S. population has
reported symptoms of a psychiatric disorder.
Delusions false beliefs held in spite of
contrary evidence have been noted for
centuries.
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
Schizophrenia affects 1% to 2% of the
population.
Dissociative thinking, or impaired logical
thought, is a key symptom.
Other symptoms include auditory hallucinations,
personalized delusions, and changes in affect
(emotion).
Figure 16.1 Not So Beautiful Voices
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
Positive symptoms are abnormal
behaviors that are gained:
Hallucinations
Delusions
Excited motor behavior
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
Negative symptoms are the result of
lost functions:
Slow thought and speech
Emotional and social withdrawal
Blunted affect or emotional
expression
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
Schizophrenia is partly heritable.
Family, twin, and adoptive studies show a
higher incidence among biological relatives.
Monozygotic (identical) twins share identical
genes dizygotic (fraternal) have half of
their genes in common.

16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
If both twins suffer from schizophrenia,
they are concordant for the disease.
If only one member of a pair has it,
they are discordant.
For identical twins, the concordance
rate is 50%, pointing to a genetic
factor.
Figure 16.2 The Heritability of Schizophrenia
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
The rate of discordance suggests that other
factors also contribute to the development of
schizophrenia:
Environmental influences
Developmental difficulties, such as low birth
weight and impaired motor coordination
Figure 16.3 Eye Tracking in Patients with Schizophrenia versus Normal People
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
Brains of some schizophrenic patients show
structural changes.
Cerebral ventricles are enlarged, especially in
males.
More-enlarged ventricles predict a poorer
response to drug treatment. (antipsychotic
drugs)
Figure 16.5 Identical Genes, Different Fates
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
The hippocampus and amygdala also
differ in schizophrenics they are
smaller.
Pyramidal cells of the hippocampus
have a disorganized arrangement,
occurring during development.
A theory is that prenatal exposure to
influenza may be the cause.
Figure 16.6 Cellular Disarray of the Hippocampus in Chronic Schizophrenia (Part 1)
Figure 16.6 Cellular Disarray of the Hippocampus in Chronic Schizophrenia (Part 2)
Figure 16.6 Cellular Disarray of the Hippocampus in Chronic Schizophrenia (Part 3)
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
The cortex also shows abnormalities of structure
and function.
Some studies show a loss of gray matter in the
frontal lobes, and PET shows less metabolic
activity.
Figure 16.8 Hypofrontality in Schizophrenia (Part 1)
The hypofrontality hypothesis schizophrenia may
be caused by underactivation of the frontal lobes.
Figure 16.8 Hypofrontality in Schizophrenia (Part 2)
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
The brain may also show neurochemical
changes.
Amphetamine psychosis caused by
repeated use of amphetamines;
resembles schizophrenia with paranoia,
delusions, and auditory hallucinations.
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
Chlorpromazine a member of the
phenothiazine family can treat
amphetamine psychosis and schizophrenia.
These neuroleptic or antipsychotic drugs
work by blocking dopamine D
2
receptors.
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
Typical neuroleptic drugs are all
antagonists at dopamine D2 receptors.
The dopamine hypothesis schizophrenia
results from excess synaptic dopamine or
increased postsynaptic sensitivity to it.
Figure 16.9 Antipsychotic Drugs that Affect Dopamine Receptors (Part 1)
Figure 16.9 Antipsychotic Drugs that Affect Dopamine Receptors (Part 2)
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
Antipsychotic drugs have long-term effects,
such as dyskinesia distortion in voluntary
movement
Tardive dyskinesia shows repetitive
movements involving the face, mouth, lips,
and tongue.
Supersensitivity psychosis can emerge
when drug doses are lowered and receptors
upregulate.
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
Problems with the dopamine hypothesis:
Schizophrenics have normal DA metabolite
levels
Drugs block D
2
receptors much faster than
symptoms are reduced
Some patients show no change
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
A new class of drugs that successfully treat
schizophrenia does not support the
dopamine hypothesis.
Atypical neuroleptics, like clozapine, block
serotonin receptors as well as D
2
receptors.
Some actually increase dopamine levels in the
frontal cortex.
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
The glutamate hypothesis schizophrenia is
caused by underactivation of glutamate
receptors.
Phencyclidine (PCP) is a psychotomimetic,
producing both positive and negative
symptoms of schizophrenia.
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
PCP acts as a NMDA receptor antagonist, and
prevents glutamate from acting normally.
When NMDA receptor underactivation is
prolonged over long periods, symptoms
ranging from memory loss to acute
schizophrenia emerge.
Figure 16.10 The Effects of PCP on the NMDA Receptor (Part 1)
Figure 16.10 The Effects of PCP on the NMDA Receptor (Part 2)
16 Schizophrenia Is the Major Neurobiological Challenge in
Psychiatry
An integrative model suggests that
schizophrenia will develop if a
compromised brain is exposed to
environmental stressors.
Examples are stresses of city life, prenatal
exposure to influenza, and loss of oxygen
at birth.
Figure 16.11 A Model of the Interaction of Stress and Brain Abnormalities in Schizophrenia
16 Mood Disorders Are a Major Psychiatric Category
Depression most common mood
disorder, characterized by:
Unhappy mood
Loss of interest, energy, and appetite
Difficulty in concentration
Restless agitation
16 Mood Disorders Are a Major Psychiatric Category
Unipolar depression depression
that alternates with normal emotional
states
Depression may last for several
months.
Inheritance is a factor in depression.
16 Mood Disorders Are a Major Psychiatric Category
Brain changes with depression:
Increased blood flow to the frontal cortex
and amygdala
Decreased blood flow to areas involving
attention and language ()

Figure 16.12 Brain Activity Patterns in Depression
16 Mood Disorders Are a Major Psychiatric Category
Neurochemical theories of depression:
The monoamine hypothesis suggests
depression is caused by reduced
synaptic activity of norepinephrine and
serotonin
Monoamine oxidase (MAO) is an
enzyme that inactivates monoamines.
16 Mood Disorders Are a Major Psychiatric Category
Treatment with monoamine oxidase (MAO)
inhibitors raises the level of monoamines
at the synapse. (MAOI ~ antidepressant)
Reserpine, a drug which reduces
monoamines in the brain, can cause
depression.
16 Mood Disorders Are a Major Psychiatric Category
Electroconvulsive shock therapy
(ECT) induction of a seizure
ECT induces release of monoamines.
Transcranial magnetic stimulation
(TMS) appears to alter the
metabolism of monoamine
transmitters.
16 Mood Disorders Are a Major Psychiatric Category
Serotonin deficiency is important in
depression.
Selective serotonin reuptake inhibitors
(SSRIs) are antidepressants that block the
reuptake of serotonin at synapses.
16 Mood Disorders Are a Major Psychiatric Category
Problems with theory of serotonin
reduction as a cause of depression:
Long lag time between treatment and
reduction of symptoms
Not everyone is cured, or even
helped
SSRIs increase risk of suicide in
children and adolescents
16 Mood Disorders Are a Major Psychiatric Category
People with Cushings syndrome have
high levels of glucocorticoids and are
prone to depression.
Symptoms of depression, obesity, and
body hair suggest dysfunction of the
hypothalamicpituitaryadrenal axis.
Figure 16.13 The HypothalamicPituitaryAdrenal Axis in Depression (Part 1)
Figure 16.13 The HypothalamicPituitaryAdrenal Axis in Depression (Part 4)
16 Mood Disorders Are a Major Psychiatric Category
The dexamethasone suppression test can
show excess cortisol release seen in
suicide victims and depressed patients.
Dexamethasone, a synthetic glucocorticoid,
can suppress cortisol release in normal
people, but not in depressed patients.
Figure 16.13 The HypothalamicPituitaryAdrenal Axis in Depression (Part 2)
Figure 16.13 The HypothalamicPituitaryAdrenal Axis in Depression (Part 3)
16 Mood Disorders Are a Major Psychiatric Category
More women than men suffer from
depression.
May reflect patterns of help-seeking
May have a psychosocial explanation,
such as social discrimination
Gender differences in endocrine
physiology
16 Mood Disorders Are a Major Psychiatric Category
Sleep is altered by depression.
Stages 3 and 4 of slow-wave sleep are
reduced.
Patients enter REM sleep very quickly, with
an increase of REM sleep in the first half
of the night.
Suppressing REM sleep may help with
depression.
Figure 16.14 Sleep and Depression (Part 1)
Figure 16.14 Sleep and Depression (Part 2)
16 Mood Disorders Are a Major Psychiatric Category
Seasonal affective disorder (SAD) is
a type of depression brought on by
the shorter days of winter.
Phototherapy administered in the
morning can suppress melatonin, a
hormone that may be important in
controlling sleep.
SAD may also respond to SSRIs.
16 Mood Disorders Are a Major Psychiatric Category
Animal models can help study depression.
In learned helplessness, an animal is
exposed to a repetitive stressful stimulus.
Learned helplessness is also linked to a
decrease in serotonin function.
giving up depression
Antidepressants reverse it.
16 Mood Disorders Are a Major Psychiatric Category
Bipolar disorder is characterized by
periods of depression alternating with
expansive mood, or mania.
The rate of cycling varies rapid
cycling consists of four or more
cycles in one year.
Some individuals may cycle several
times in one day.
16 Mood Disorders Are a Major Psychiatric Category
Cyclothymia, a milder form of bipolar
disorder patients cycle between
dysthymia (mild depression) and
hypomania (increased energy).
Lithium is a mood-stabilizing drug
used to treat bipolar disorder it
seems to interact with the circadian
clock.
Figure 16.15 Functional Images of Bipolar Disorder
16 There Are Several Types of Anxiety Disorders
Phobic disorders intense irrational
fears centered on an object, activity,
or situation that a person avoids
Anxiety disorders: panic disorder
recurrent attacks of intense
fearfulness; and generalized anxiety
disorder persistent, excessive
anxiety, and worry
16 There Are Several Types of Anxiety Disorders
Benzodiazepines are anxiolytic
drugs used to treat anxiety.
They bind to GABA receptors and
enhance GABAs inhibitory actions.
Serotonin agonists and SSRIs are also
used to treat anxiety.
Figure 16.16 The Distribution of Benzodiazepine Receptors in the Human Brain
16 There Are Several Types of Anxiety Disorders
In posttraumatic stress disorder
(PTSD), unpleasant memories
repeatedly plague the victim.
PTSD victims show:
Memory changes, such as amnesia
Flashbacks
Deficits in short-term memory
16 There Are Several Types of Anxiety Disorders
PTSD victims have decreased volume
in the right hippocampus may be a
risk factor rather than a consequence.
Fear conditioning is learning in which
fear is associated with a neutral
stimulus.
16 There Are Several Types of Anxiety Disorders
Persistent memories and fears in
PTSD may be a failure to forget.
Projections to the amygdala may lose
effectiveness in suppressing fear.
PTSD victims may have an increased
response to stress hormones.

Figure 16.17 A Neural Model of Posttraumatic Stress Disorder
16 There Are Several Types of Anxiety Disorders
Obsessivecompulsive disorder
(OCD) is marked by recurring,
repetitive acts.
In OCD patients:
Routine acts become compulsions
Recurrent thoughts become
obsessions
16 There Are Several Types of Anxiety Disorders
Serotonin plays a major role in OCD,
in the orbitofrontal prefrontal cortex.
OCD is heritable, and may also be
triggered by infections.
OCD is often co-morbid with
Tourettes syndrome they occur
together.
16 There Are Several Types of Anxiety Disorders
OCD and Tourettes syndrome involve
disorders of the basal ganglia.
Drug therapy in Tourettes syndrome
has focused on dopamine rather than
serotonin.
D
2
receptors are denser in the caudate
nucleus of a Tourettes sufferer.
Box 16.3 Tics, Twitches, and Snorts: The Unusual Character of Tourettes Syndrome
16 Neurosurgery Has Been Used to Treat Psychiatric Disorders
Psychosurgery uses brain lesions
to modify severe psychiatric disorders.
Lobotomy disconnects parts of the
frontal lobe from the rest of the brain.
More localized lesions have proven
more effective.
16 Neurosurgery Has Been Used to Treat Psychiatric Disorders
Cingulotomy lesions of the cingulate
cortex to treat anxiety, depression,
and OCD
Capsulotomy lesions of the internal
capsule, to treat anxiety disorders
Deep brain stimulation through
implanted electrodes can be effective.
Figure 16.18 Neurosurgery to Treat ObsessiveCompulsive Disorder (Part 1)
Figure 16.18 Neurosurgery to Treat ObsessiveCompulsive Disorder (Part 2)
16 Abnormal Prion Proteins Destroy the Brain
Prions abnormally folded proteins
that lead to brain degeneration
Scrapie a fatal disease in sheep,
caused by prions
16 Abnormal Prion Proteins Destroy the Brain
Bovine spongiform encephalopathy
(BSE, or mad cow disease) the
bovine form of scrapie
CreutzfeldtJakob disease (CJD)
the human disorder, causing
dementia, sleep disorders,
schizophrenia-like symptoms,
and death
Figure 16.19 The Culprits of Mad Cow Disease