1. Schizophrenia Famous schizophrenics: Hölderlin Maupassant Lenz Walser, Robert Proust Strindberg Lenau

2. Prevalence 1 % throughout the world

3. Time course Begins during young adulthood: in males 21-25 years in females 28-32 years Generally progressive (if untreated) Begins with Positive symptoms after years negative symptoms dominate

4. Positive symptoms Disordered thoughts Delusions (f.e. the belief that one is being persecuted or that one‘s feelings, thoughts and actions are controlled by an outside force Hallucinations, usually auditory hearing voices commenting on one‘s actions Negative symptoms Loss of normal association between ideas, incoherence of ideas Poverty of speech Flattening, loss, or iadequate affect Social withdrawal

6. Causes Genetic disposition/vulnerability Two hit hypothesis: 50% genetic 50 % second hit ??? Second hit: Birth hypoxia Stress Cannabis use Psychostimulant use

7. Morphological findings Enlargement of the 3rd ventricle Reduced volume of the corpus callosum ??? Disturbed layerd arrangement of Hippocampus??? prefront. Cortex???

8. Neurochemical findings Dopamine hypothesis: A Dopamine hyperactivity underlies the disease Regional selectivity hypothesis: Dopamine hyperactivity in the meso-accumbal/limbic system Dopamine hypoactivity in the prefrontal cortex Glutamate hypothesis: A Glutamate hypoactivity underlies the disease

9. Behavioural pharmacology Animal models of Schizophrenia: Pharmacological induction of dopamine hyperactivity Pharmacological induction of glutamate hypoactivity Developmental models Genetic models (breeding the endophenotype)

10. Typical antipsychotics Chlorpromazine, Haloperidol Effect:block DA receptors; counteract mainly positive symptoms Sideeffects: Parkinsonism Atypical antipsychotics Clozapine, Olanzapine, Sertindole, Effect: Receptor? counteract positive and negative symptoms/depression Side effects: No parkinsonism New generation Aripiprazol Partial Dopamine agonists: Anatgonists in n. accumbens Agonists in prefront. cortex

11. Psychostimulant-induced psychosis …the psychosis that arises from repeated administration of cocaine or amphetamine results from sensitization… (Robinson and Becker 1986) A role for sensitization in psychostimulant-induced Paranoia and psychosis (Kalivas et al. Mojacar meeting 1998) 1.The development of psychostimulant psychosis requires a prolonged period of abuse in nonschizophrenic individuals. 2. Relapse psychosis can occur following reexposure to a lower dose of drug than that associated with initial psychosis. 3. Sensitivity to drug-induced psychosis persists even after years of abstinence, indicating enduring psychostimulant-induced changes in neural function.

12. Schizophrenia and sensitization Dysregulated dopamine/glutamate balance Attribution of aberrant salience to stimuli, Aberrant sense of novelty Delusions to explain the aberrant salience Antipsychotics block dopamine receptors within hours Dampening of salience of encountered stimuli by way of desensitization/unlearning salience within some weeks