Discussion Preview 6 Biology of Psychopathology

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Discussion Preview 6Biology of Psychopathology
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Decoding Schizophrenia

• This study was a research study.
• Originally, it was hypothesized that excess
  dopamine in certain brain areas caused
  schizophrenic behavior.
• Since then, some researchers modified the
  hypothesis stating that negative and cognitive
  dysfunction may be caused by too little dopamine
  in certain areas (frontal lobes) and too much in
  other areas (limbic system).
• Drug experimentation has given rise to the
  question whether the NMDA receptor for glutamate,
  the main excitatory neurotransmitter in the
  brain, is blocked and if glutamate dysfunction
  could be the underlying cause of schizophrenia.

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Decoding Schizophrenia / Summary

• Approximately 1 of the worlds population has
  schizophrenia and have below average
  intelligence.
• Inheritance can predispose individuals to
  schizophrenia and environmental factors (prenatal
  infections, malnutrition, birth complications,
  and brain injuries) can increase the risk.
• Individuals with schizophrenia have smaller
  brains than those unaffected of the same age and
  sex.

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Decoding Schizophrenia / Summary, cont

• Symptoms of schizophrenia are
• positive include agitation, paranoid
  delusions, hallucinations (spoken voices), and
  command hallucinations (voices that tell them to
  hurt themselves or others),
• negative and cognitive include autism (loss of
  interest in people or environment), ambivalence
  (lack of emotion), blunted affect (lack of facial
  expression), and loose association (jumbling
  words and thoughts into a word salad).

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Decoding Schizophrenia / Summary, cont

• Antipsychotics stop all symptoms in about 20 of
  patients. One-third of patients show no
  significant improvement from this medication.
• 1950s, the theory that schizophrenia was
  dopamine-related surfaced
• Drugs, known as phenothiazines, were beneficial
  in the control of positive symptoms but were
  inadequate in treating those patients with a slow
  onset of symptoms, where negative symptoms were
  more prominently expressed.

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Decoding Schizophrenia / Summary, cont

• So why do some individuals respond completely to
  dopamine treatment and others do not?
• Hypothesis modified stating negative and
  cognitive dysfunction may be caused by too little
  dopamine in certain areas (frontal) and too much
  in other areas (limbic).
• More research1960s
• PCP (angel dust) and ketamine (an anesthetic with
  similar effects of PCP) used during controlled
  drug-challenge trials, manifest symptoms of
  schizophrenia. These drugs block the NMDA
  receptor for glutamate, the main excitatory
  neurotransmitter in the brain.

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Decoding Schizophrenia / Summary, cont

• 1980s, researchers found new drugs that were
  more effective in the treatment of negative and
  positive symptoms clozapine (clozaril) that
  inhibits dopamine receptors and the activity of
  other neurotransmitters in the brain
• The new drug finding led to the discovery that
  other neurotransmitters were involved in
  schizophrenia.

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Decoding Schizophrenia / Conclusion

• Most important finding
• No one area of the brain is responsible for
  schizophrenia.
• In normal brain function, the brain, as a whole,
  coordinates its action harmoniously in and
  between the different regions however,
  schizophrenic patients have abnormal levels of
  brain function in and between several brain
  regions (frontal, temporal, and occipital lobes,
  etc.).

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Dysfunction in the glutamate receptor, NMDA,
critical for brain development, learning, memory,
neural processing, that participates in
regulating dopamine release, may prompt
schizophrenic symptoms.
Decoding Schizophrenia / Conclusion cont

• In laboratory animals, the drug clozapine has
  shown to reverse the behavioral effects of PCP.
• Long-term clinical trials have begun for a new
  class of medicine that activates NMDA receptors
  to treat both negative and cognitive symptoms.
• Drug therapy seems to be the most hopeful
  treatment for schizophrenia.

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Decoding Schizophrenia / Implications

• This study aides researchers in their
  understanding of schizophrenia, which brain areas
  are affected, and which neurotransmitters are
  involved.
• This study also supplies better understanding of
  drugs that may greatly reduce the effects of
  schizophrenia.

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A Man Who Borrowed Cars
This case study is about a 51 year old man who at
the age of 33 had a subarachnoid hemmorhage due
to a ruptured aneurysm of the anterior
communicating artery. He had an operation to
repair the aneurysm and during the operation it
ruptured again and the right pericallosal artery
had to be clipped. Since the aneurysm he has
suffered from abnormal, destructive behavior. He
was evaluated to determine if a mesial
orbitofrontal cerebral lesion caused his
behavioral differences.
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A Man Who Borrowed Cars / Summary

• Prior to aneurysm, up to age 33 years
• Married
• Father
• Dependable
• Punctual
• Worked for 10 years at a car factory test driving
  cars
• After the aneurysm, behavioral changes addressed
• Idleness
• Depression
• Compulsive stealing of employers cars
• Tardiness
• Failure to hold a job
• Incarceration

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A Man Who Borrowed Cars / Summary, cont

• Hypothesis the mesial orbitofrontal cerebral
  lesion caused the patients behavioral
  differences.

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A Man Who Borrowed Cars / Conclusion

• Testing, affected brain areas, and diagnosis
• Clinical examination was normal.
• Neuropsychological screening was normal for
  language, attention, calculation, motor
  coordination, visuospatial processing, and
  reasoning.
• Tests of prefrontal function were normal
  Wisconsin card-sorting test, Stroop test, trail
  making test, semantic and phonemic word
  generation, serial subtraction, and subtests of
  the WAIS-R.
• CT-scan revealed a small lesion in the right
  orbitofrontal paramesial region.

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A Man Who Borrowed Cars / Conclusion, cont

• Single-photon emission CT (SPECT) showed a
  drastic reduction of blood flow in the right
  orbitofrontal paramesial region.
• Mesial orbitofrontal cerebral lesion had caused
  behavioral changes that were contrary to what had
  been observed prior to the aneurysm.

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A Man Who Borrowed Cars / Implications

• From this case study, we can conclude that lesion
  disorders may manifest symptoms without positive
  confirmation on neuropsychological tests
  therefore, a wide variety of testing (including
  SPECT) should be performed to ensure a proper
  diagnosis.
• After the diagnosis, records of such lesion
  damage should be made available to aide in
  proper treatment and to protect patients legally,
  from improper prosecution.

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Questions for discussion

• Which neurotransmitter has been recognized that
  could explain the wide range of symptoms in
  schizophrenia and what are the functions of this
  neurotransmitter?
• Describe the brain pathways affected from the
  mesial orbitofrontal cerebral lesion and the
  abnormal behaviors experienced by the patient in
  A man who borrowed cars.

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References

• Angladette, L., Benoit, N., Cohen, L.,
  Pierrot-Deseilligny, C. A man who borrowed cars.
  The Lancet. London January 2, 1999. Vol 353.
• Coyle, J., Javitt, D. Decoding schizophrenia.
  Scientific American. Jan. 2004. Vol. 290, Iss. 1
  p. 48, 8p, 5c.