1. Schizophrenia Lesson 26

2. n Disordered thoughts & bizarre behavior l 1 percent of population l equal among sexes n Progressive? l can only manage symptoms n Symptoms > 6 mo l 2 classes of symptoms l Positive l Negative ~ Schizophrenia

3. Positive Symptoms n Thought disorders l incoherence l loose associations n Delusions l bizarre beliefs l persecution, grandeur n Hallucinations l sensory experiences l no external stimuli ~

4. Negative Symptoms n Poverty of speech l little spontaneous speech n Poverty of emotion l Flattened, inappropriate affect n Social withdrawal l lack of personal hygiene ~

5. Positive Symptoms n Thought disorders l incoherence l loose associations n Delusions l bizarre beliefs l persecution, grandeur n Hallucinations l sensory experiences l no external stimuli ~

6. Negative Symptoms n Poverty of speech l little spontaneous speech n Poverty of emotion l Flattened, inappropriate affect n Social withdrawal l lack of personal hygiene ~

7. Anatomical Indicators n Increased ventricle size l 67% of cases n brain atrophy l HC l thalamus (Nancy Andresen, UI) l general atrophy ~ N S S

8. Heritability n General Population 1% l One parent schiz. 17% l DZ twins 17% l MZ twins 50% n Strong genetic component l predisposition + stressor n Adoption Studies l risks more like biological parents n Evidence of gene(s) elusive ~

9. The Dopamine Hypothesis n Positive symptoms l too much DA activity l Not excessive DA levels l Maybe overabundance of receptors n 2 major DA systems l Mesolimbic l Nigrostriatal ~

10. Nucleus Accumbens Limbic System Striatum VTASN Nigrostriatal pathway Mesolimbic pathway Major DA Pathways Ventral Tegmental Area Substantia Nigra

11. DA Hypothesis: Evidence n Therapeutic Drugs l Neuroleptics (Antipsychotics) l DA antagonists n DA agonists l amphetamines, cocaine, etc. l induce symptoms n Problem: delay in effects ~

12. 1 st Generation Neuroleptics n Relieve only positive symptoms n Chlorpromazine (Thorazine) l phenothiazines l primarily blocks D 1 & D 2 n Haloperidol (Haldol) l butyrophenones l primarily blocks D 2 n D 2 -R affinity and clinical potency ~

13. Strength of D2 binding Therapeutic effects Hi Lo Chlorpromazine Haloperidol Spiroperidol

14. 1 st Generation: Side Effects n Motor l Nigrostriatal pathway l Tardive Dyskinesia l Parkinson-like symptoms n Sedation l low compliance ~

15. 2 nd Generation Neuroleptics n Block DA and 5-HT receptors l Relieve positive & negative symptoms l Lower Parkinson’s-like side effects n Clozapine (Clozaril) l high risk agranulocytosis n Risperidone (Risperidal) l low risk of agranulocytosis ~