Schizophrenia

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Schizophrenia

• Medicinal Chemistry
• Spring 2008
• Julie Kornder

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Schizophrenia

• Definition a brain disorder resulting in a
  skewed perception of reality and the inability to
  differentiate between real vs. unreal experiences
  and normal vs. abnormal emotional responses and
  social behavior.
• Image by Louis Wain

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Common Schizophrenic Symptoms

• Delusions
• Disorganized Thinking
• Suspicious Behavior
• Antagonistic Behavior
• Auditory Hallucinations
• Feeling Unfairly Victimized
• Feeling Strange Things are Happening

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4 Main Types of Schizophrenia

• The Paranoid
• The Hebephrenic
• The Catatonic
• The Simple

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Proposed Causes of Schizophrenia

• Environmental
• Childhood Development
• Drug Use Related
• Genetic
• Parasite Toxoplasma gondii from Cats
• Neurodevelopment
• Dopamine Hypothesis
• NMDA Receptor Hypothesis
• Pre-Pulse Inhibition (Sensory Filtering)
• Single-carbon Hypothesis
• Membrane Hypothesis

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Bio-Psycho-Social Model
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Diagnosis

• Psychiatrists correct interpretation of abnormal
  behaviors
• Exclusion of other illnesses with similar
  symptoms
• Abnormalities in dopamine concentration and
  density of dopamine binding sites examined
  post-mortem
• Twin Studies (MRI showing enlarged ventricles)
• Future Techniques
• Positron Emission Tomographic (PET) Screening
• Electroencephalograph (EEG)

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Other Facts

• Affects 1 worlds population
• Onset
• Males Late Teens
• Females Late Twenties

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Neurochemistry of Schizophrenia

• Successful treatments lead to understanding of
  underlying process.
• 5 subtypes of Dopamine receptors (D1-D5)
• Antipsychotic agents antagonize the dopaminergic
  receptors D2 and D3.
• Blocking D2 receptors may have side effects.
• D3 antagonists may have better properties as
  antipsychotics.

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Treatment

• Rehabilitation
• Self Help
• Individual Psychotherapy
• Family Education Therapy
• Antipsychotic Medications
• Reduce Anxiety
• Reduce Hallucinations and Delusions
• Reduce Risk of Suicide
• Antidepressants
• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Tricyclic Antidepressants

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Drug Therapy

• Alkaloids from Roots of Rauwolfia (antipsychotic
  plant from India)
• Group Phenothiazines
• e.g. Chlorpromazine
• Discovery 1952 Henry Laborit
• Antihistamine (relax during surgery)
• Later found that it blocked dopamine
• Livestock antihelminthic (anti-worm)
• Urinary Antiseptic
• Discontinued use due to Toxicity
• Clozaril
• Seroquel
• Haloperidol

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Further Investigations for Paper

• Interview
• History of Schizophrenia
• 1st identified by Dr. Emile Kraepelin (1887)
  "dementia praecox"
• Swiss psychiatrist, Eugen Bleuler - coined term
  "schizophrenia" (1911)
• Neural Degradation
• Drug Development
• Comparison of Drugs

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References

• Micromedex-Drugs.com. Schizophrenia. Jan 2008.
  Feb 2008. lthttp//www.drugs.com/condition/schizoph
  renia.htmlgt.
• Deth, Richard C. (1999) What happens to the body
  and brain of individuals with schizophrenia?
  Scientific American.
• Bebbington, Paul and Peter McGuffin.
  Schizophrenia The Major Issues. London 1988,
  Heinemann Professional Publishing.
• Arieti, Silvano, M.D. Interpretation of
  Scizophrenia, 2nd Ed. New Jersey 1994, Jason
  Aronson Inc.
• Patrick, Graham L. An Introduction to Medicinal
  Chemistry, 3rd Ed. New York 2005, Oxford
  University Press.

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The End

• Thanks!