Schizophrenia

1. Schizophrenia Medicinal Chemistry Spring 2008 Julie Kornder

2. 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

3. Common Schizophrenic Symptoms Delusions Disorganized Thinking Suspicious Behavior Antagonistic Behavior Auditory Hallucinations Feeling Unfairly Victimized Feeling Strange Things are Happening

4. 4 Main Types of Schizophrenia The Paranoid The Hebephrenic The Catatonic The Simple

5. 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

6. Bio-Psycho-Social Model

7. Diagnosis Psychiatrist�s 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)

8. Other Facts Affects 1% world�s population Onset Males � Late Teens Females � Late Twenties

9. 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.

11. 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

12. 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

13. 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

15. References Micromedex-Drugs.com. �Schizophrenia.� Jan 2008. Feb 2008. <http://www.drugs.com/condition/schizophrenia.html>. 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.

16. The End Thanks!