Psychotic Disorders

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Psychotic Disorders

• DSM-IV

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Psychosis

• Psychosis is a condition characterized by a loss
  of contact with reality.
• Hallucinations false perceptions
• Delusions false beliefs

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Examples of Hallucinations and Delusions

• Hallucinations
• Hearing voices
• Seeing visions
• Experiencing odd tastes, smells
• Experiencing odd feelings

• Delusions
• Persecution
• Grandeur
• Somatic
• Jealousy
• Erotomania
• Thought control
• Behavior control
• Thought withdrawal

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Some Recent Cases

• Ted Kaczynski--the unabomber
• Mark David Chapman--killed John Lennon
• John Hinckley--shot President Reagan
• Andrea Yates--drowned her five children
• John Nashthe subject of the movie A Beautiful
  Mind
• Note most schizophrenics are not violent

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Ted Kaczynski the unabomber

• Taught mathematics at UC Berkeley

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Mark David Chapman killed John Lennon

• Diagnosed as Schizophrenic.

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Andrea Yates after she was arrested
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John Hinckley

• Still in St. Elizabeths

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Heavens Gate Cult

• Marshall Applewhite instructed his followers to
  kills themselves when the comet Hale-Bopp
  arrived. They were all dressed alike. UFO cult

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Heavens Gate Cult

• Doomsday cult centered in California. Founded in
  1975 by Marshall Applewhite Bonnie Nettles.
  They thought they were the Two Witnesses
  mentioned in the Book of Revelation. They lived
  communally in a large San Diego country home.
  Little contact with family or friends--even their
  own children. They dress in unisex clothing
  white shirts and black pants. They are required
  to be celibate. Eight of the male members along
  with Applewhite were willingly castrated. They
  believed this prepared them for the next level of
  existence, a life that would be free of gender,
  sexual identity, and sexual activity.
• They followed a syncretistic religion combining
  elements of Christianity with unusual beliefs
  about the nature of UFOs. They interpreted
  passages from the four gospels and the Book of
  Revelation as referring to UFO visitation. They
  look at earth as being in control of the evil
  forces, and the group members see themselves as
  being among the elite who would attain heaven.
• 21 women and 18 men committed suicide in 3 groups
  on 3 successive days. (He spent some time in
  Houston).

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Psychoses may be caused by

• Drugs e.g., LSD, Amphetamines, Cocaine
• Brain Diseases e.g., Alzheimers Disease
• Brain Injuries e.g., trauma, stroke
• Extreme stress e.g., war, kidnapping,
• Bipolar and major depressive disorders
• Schizophrenia--most common cause

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A few facts about schizophrenia

• Usually diagnosed in late teens/early 20s
• Means split mind Eugen Bleuler
• Affects approximately 1 of people
• Men have more severe cases
• 10-15 commit suicide 1
• More common among the poor

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Diagnosing Psychiatric Disorders

• All psychiatric disorders including schizophrenia
  are diagnosed on the basis of clusters of
  symptoms.
• There is no brain scan, no urine test, no blood
  test, no cerebral spinal fluid test that can be
  used to diagnose schizophrenia. There is no
  independent biological test at this time.

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Positive and Negative Symptoms

• Positive
• Hallucinations
• Delusions
• Disordered speech
• Bizarre behavior
• Good response to drugs, normal brain ventricles,
  limbic system abnormalities

• Negative
• Emotionally flat
• Poverty of speech
• Associality
• Apathy
• Avolition
• Frontal lobe abnormalities, enlarged ventricles,
  variable response to drugs

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Positive Symptoms Type I

• Delusions
• Persecutory
• Delusions of reference
• Grandiose delusions
• Delusions of thought insertion
• Hallucinations
• Disorganized Thought and Speech
• Disorganized or Catatonic Behavior

Painting by schizophrenic patient
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Negative Symptoms Type II

• Flattened/Blunted affect
• Severe reduction or absence of affect (mood,
  emotion)
• Alogia
• Severe reduction or absence of speech
• Avolition
• Inability to persist at common, goal-oriented
  tasks

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Diagnostic Criteria for Schizophrenia (DSM IV)

• Delusions
• Hallucinations
• Disorganized Speech
• Disorganized or catatonic behavior
• Negative Symptoms (deficits)
• Two or more of the above must be present for at
  least one month and some disturbance for six
  months
• Significant impairment in social/occupational
  functioning

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Clinical Syndromes Schizophrenia

• General symptoms
• Delusions and irrational thought
• Deterioration of adaptive behavior
• Hallucinations
• Disturbed emotions
• Disorganized speech
• Prognostic factors

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Disorganized Speech

• Disorder of thought form
• Loose Associations
• Thought derailment
• Neologisms (making up words)
• Word salad

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Subtyping of Schizophrenia

• 4 subtypes
• Paranoid type
• Catatonic type
• Disorganized type
• Undifferentiated type
• New model for classification
• Positive vs. negative symptoms

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Etiology (Causal Factors)

• No one factor can fully explain
• Very good evidence for genetic transmission of a
  predisposition
• Might be polygenic
• Suspect chromosomes 22, 6, 8, and 1
• Mutations early in development (see later slide)
• Some evidence for other biological factors

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Genetic Studies

• Family studies risk increases as number of
  shared genes increases
• Twin studies concordance rate higher in
  identical than fraternal twins
• Adoption studies biological relatives show
  increased risk

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Other suggested causal factors

• Prenatal viral infections, esp. 4 -7 month
• Rh incompatibility between mother and baby
• Early nutritional deficiencies
• Birth complications

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Etiology of Schizophrenia, cont.

• Genetic vulnerability
• Neurochemical factors
• Structural abnormalities of the brain
• The neurodevelopmental hypothesis
• Expressed emotion
• Precipitating stress

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Other Biological Aspects

• Enlarged ventricles
• 3 reduction in overall brain volume
• Amygdala, frontal lobes, temporal lobes,
  hippocampus, thalamus
• Most brains look normal
• Dopamine
• Glutamate (see below)

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Structural Brain Damage

• Enlarged ventricles suggest deterioration /
  atrophy of brain tissue
• Differences in volume, density, metabolic rate
• Especially in pre-frontal cortex
• Exist in individuals w/ family history of illness
  but no symptoms

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Neurotransmitters Role of Dopamine

• Excess number of dopamine receptors
• related to positive symptoms
• Less dopamine activity in prefrontal cortex
• associated with negative symptoms
• Receptors in mesolimbic pathway
• Atypical antipsychotics (e.g. clozapine) block
  action of dopamine in this system

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The dopamine hypothesis as one explanation for
schizophrenia
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Treatment

• Antipsychotic medications
• Thorazine (conventional, typical)
• Tardive dyskinesia serious side effect
• Clozaril (atypical)
• Case Management
• Family Therapy
• Psychotherapy usually NOT appropriate

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Expressed Emotion
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Where do schizophrenics end up?
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Very Recent Drug Research

• Worldwide sales for psychiatric drugs almost
  50 billion annually
• Most antipsychotic drugs for schizophrenia target
  dopamine side effects can include diabetes,
  acne, weight gain, impotence, etc. Efficacy
  variable.
• The newest drug research is targeting glutamate

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Glutamate

• People who use PhencyclidinePCP have
  hallucinations, delusions, etc., similar to
  schizophrenia
• In 1979, researchers found that PCP blocked the
  release of glutamate at the glutamate receptors
  NMDA AMPA
• These receptors seem to modify the amount of
  glutamate that cells released rather than simply
  turning circuits on and off (they fine- tune
  signals)

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Glutamate cont.

• Molecular biologists (1990s) discovered genes
  for 8 metabotropic glutamate receptors. Dr.
  Schoepp others tried to find chemicals that
  would either block or trigger the receptors
  selectively.
• Dr. Moghaddam, at Yale, demonstrated that
  activating metabotropic glutamate receptors in
  rats could reverse the effects of PCP--providing
  proof that altering the path of glutamate
  transmission in the brain might relieve the
  symptoms of psychosis.

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Glutamate competition begins

• Dr. Schoepp then developed a drug and tried it on
  people in a clinical trial (at Eli
  Lilly-LY404039)) with relatively good success.
  Although slightly less effective than Zyprexa it
  had fewer side effects and seemed to improve
  cognitive symptoms. The next step is a larger
  clinical trial.
• Competition among drug companies to find an
  effective drug that works on glutamate receptors
  is intensifying because this is a huge market.

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Brand new genetic research(Science, March 28,
2008)

• New gene-scanning technology detected extremely
  rare and unknown mutations that turned up 3 to 4
  times as often in schizophrenics as in those w/o
  it.
• The genetics of schizophrenia appear to be more
  complex than thought.
• The study was a collaboration of NIMH, the
  University of Washington, Seattle, and Cold
  spring Harbor Lab.

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Science, 2008 cont.

• Analyzed blood samples from 150 people with
  schizophrenia and 268 without.
• Technique scans the entire human DNA map and look
  for rare variations. Some mutations are
  inherited others occur spontaneously during or
  near conception
• 53 gene altering mutations were found and were
  concentrated in genes known to be involved in
  brain development.

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Science, cont.

• Mary-Claire King, a co-author, said the findings
  helped explain several facts about schizophrenia,
  including why genetic selection has not caused it
  to disappear. A constant influx of new mutations
  that occur purely by chance, out of the blue, can
  explain the persistence of schizophrenia in all
  parts of the world and throughout human history,
  Professor King said.

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Science, cont.

• One of the mutations identified in the study,
  for instance, distorts a protein that is involved
  in guiding neurons to their proper places during
  brain development. Another mutation that turned
  up changes the shape of a molecule that
  transports glutamate, a chemical that excites
  neurons and is heavily involved in transmitting
  signals between brain cells.

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Science, reported in NYTimes

• My dream, Dr. Sebat said, is that well do
  this kind of high-resolution analysis across tens
  of thousands of people and have full catalogs of
  variations that will tell us something not only
  about schizophrenia but about bipolar disorder,
  autism, depression, all of these disorders.
• NYTimes, Friday, March 28, 2008

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Conclusions

• Schizophrenia affects about 1 of the worlds
  population and disables more people than any
  other physical or mental disorder.
• The cost to society is enormous. Direct medical
  care in the U. S. is estimated to be 20 billion
  dollars per year (Torrey, 1995). Loss of
  productivity is incalculable.
• There is excellent research going on in many
  areas-- neuroscience, genetics, molecular
  biology, psychology, pharmacology, and other
  areas. This is a challenging disorder, but we
  have every reason to be encouraged by the newest
  research findings.

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DSM-IV-TR Psychotic Disorders

• Schizophrenia 6 mos. of symptoms
• 1-2 lifetime prevalence
• Schizophreniform Disorder (1
• Brief Psychotic Disorder (1 day -
• Schizoaffective Disorder (schizo mood)
• Delusional Disorder just delusion
• islands of craziness
• Shared Psychotic Disorder (folie a deux)