Psychopathology: Biological Basis of Behavioral Disorders

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Psychopathology Biological Basis of Behavioral
Disorders
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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.

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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.

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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).

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Figure 16.1 Not So Beautiful Voices
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16 Schizophrenia Is the Major Neurobiological
Challenge in Psychiatry

• Positive symptoms are abnormal behaviors that are
  gained
• Hallucinations
• Delusions
• Excited motor behavior

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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

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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.

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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.

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Figure 16.2 The Heritability of Schizophrenia
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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

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Figure 16.3 Eye Tracking in Patients with
Schizophrenia versus Normal People
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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)

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Figure 16.5 Identical Genes, Different Fates
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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.

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Figure 16.6 Cellular Disarray of the Hippocampus
in Chronic Schizophrenia (Part 1)
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Figure 16.6 Cellular Disarray of the Hippocampus
in Chronic Schizophrenia (Part 2)
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Figure 16.6 Cellular Disarray of the Hippocampus
in Chronic Schizophrenia (Part 3)
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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.

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Figure 16.8 Hypofrontality in Schizophrenia
(Part 1)
The hypofrontality hypothesis schizophrenia may
be caused by underactivation of the frontal lobes.
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Figure 16.8 Hypofrontality in Schizophrenia
(Part 2)
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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.

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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 D2 receptors.

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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.

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Figure 16.9 Antipsychotic Drugs that Affect
Dopamine Receptors (Part 1)
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Figure 16.9 Antipsychotic Drugs that Affect
Dopamine Receptors (Part 2)
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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.

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16 Schizophrenia Is the Major Neurobiological
Challenge in Psychiatry

• Problems with the dopamine hypothesis
• Schizophrenics have normal DA metabolite levels
• Drugs block D2 receptors much faster than
  symptoms are reduced
• Some patients show no change

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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 D2 receptors.
• Some actually increase dopamine levels in the
  frontal cortex.

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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.

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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.

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Figure 16.10 The Effects of PCP on the NMDA
Receptor (Part 1)
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Figure 16.10 The Effects of PCP on the NMDA
Receptor (Part 2)
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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.

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Figure 16.11 A Model of the Interaction of
Stress and Brain Abnormalities in Schizophrenia
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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

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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.

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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 (????)

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Figure 16.12 Brain Activity Patterns in
Depression
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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.

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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.

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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.

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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.

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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

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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 hypothalamicpituitary
  adrenal axis.

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Figure 16.13 The HypothalamicPituitaryAdrenal
Axis in Depression (Part 1)
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Figure 16.13 The HypothalamicPituitaryAdrenal
Axis in Depression (Part 4)
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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.

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Figure 16.13 The HypothalamicPituitaryAdrenal
Axis in Depression (Part 2)
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Figure 16.13 The HypothalamicPituitaryAdrenal
Axis in Depression (Part 3)
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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

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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.

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Figure 16.14 Sleep and Depression (Part 1)
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Figure 16.14 Sleep and Depression (Part 2)
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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.

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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.
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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.

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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.

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Figure 16.15 Functional Images of Bipolar
Disorder
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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

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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.

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Figure 16.16 The Distribution of Benzodiazepine
Receptors in the Human Brain
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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

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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.

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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.

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Figure 16.17 A Neural Model of Posttraumatic
Stress Disorder
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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

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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.

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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.
• D2 receptors are denser in the caudate nucleus of
  a Tourettes sufferer.

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Box 16.3 Tics, Twitches, and Snorts The Unusual
Character of Tourettes Syndrome
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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.

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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.

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Figure 16.18 Neurosurgery to Treat
ObsessiveCompulsive Disorder (Part 1)
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Figure 16.18 Neurosurgery to Treat
ObsessiveCompulsive Disorder (Part 2)
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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

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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

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Figure 16.19 The Culprits of Mad Cow Disease