1.  incidence  characteristics  causes?  treatments?

3. Copyright © Allyn & Bacon 2007

4.  Schizophrenia is clearly a disease of the brain. ◦ Enlarged ventricles ◦ Prefrontal cortex

5.  Hypofunctionality of the prefrontal cortex ◦ Reduced activity in this region  concentration and focused attention

6. Copyright © Allyn & Bacon 2007

7.  positive and negative symptoms  positive symptoms – ◦ things that you can see; hallucinations, delusions, etc  negative symptoms – things that are absent ◦ social withdrawal

8.  Schizophrenia is clearly a brain disease with a genetic basis

9.  twin studies ◦ look at monozygotic (1 egg) twins – 99% genes in common vs dyzgotic twins – 50% genes in common ◦ look at concordance rates – proportion of cases in which both twins have the disorder

12.  family studies ◦ allows you to look at increased concordance rates (particularly in first-degree relatives)

14.  Adoption studies ◦ allows you to look at role of environment vs genes

15.  role of stress? ◦ stress does not cause schizophrenia BUT  viral exposure?

17.  role of stress? ◦ stress does not cause schizophrenia BUT  viral exposure?  fetal insult? ◦ hypoxia, etc

18.  positive symptoms – could be treated medically  negative symptoms – would not respond to drugs but rather was brain damage as a consequence of whatever schizophrenia did to the brain

19.  1950’s - first drugs to treat schizophrenia appeared  called traditional neuroleptics, antipsychotics ◦ treat the positive symptoms  Now – atypical neuroleptics – 1989 – 1999 ◦ treat positive and negative symptoms

20.  1950’s – chlorpromazine (Thorazine) and haloperidol (Haldol) ◦ cheapest way to treat positive symptoms, still widely used  many other uses for chlorpromazine ◦ nausea and vomiting, chronic hiccups, severe itching, manage psychotic component in acute mania, to treat alcohol hallucinosis

21.  Blocking DA receptors  Resulted in the DA theory for schizophrenia  D2 receptor subtype important ◦ how well the drug binds to D2 receptor is clearly linked to reduction in positive symptoms

22.  drugs that block DA;  drugs that increase DA activity  l-dopa ◦ used to treat Parkinsons Disease ◦ potential side effect:  amphetamine and cocaine ◦ acute psychosis  ephedrine

23.  mesolimbic DA pathway – emotion  nigrostriatal DA pathway –movement  mesocortical DA pathway – ◦ higher cognitive function  tuberofundibular DA pathway – ◦ within the hypothalamus – controls the release of certain hormones

24.  a lot of problems related to movement ◦ parkinson like symptoms ◦ spastic muscle contractions in head and neck ◦ restlessness, constant movement ◦ tardive dyskinesia

25.  NO! – these drugs have effects on multiple other neurotransmitters that also have significant side effects  block ACh as one ◦ memory deficits, dry mouth, urinary retention,

26.  first atypical neuroleptic was clozapine ◦ effective in proportion of patients that were unresponsive to previous medication

27.  first atypical neuroleptic was clozapine  people who had not been able to leave hospital for 25 years were suddenly better!

28.  first atypical neuroleptic was clozapine ◦ effective in proportion of patients that were unresponsive to previous medication ◦ reduced negative symptoms ◦ reduced tardive dyskinesias ◦ risky side effects – agranulocytosis (potentially lethal drop in white blood cells ~ 1% of people on drug)

29.  Initially, clozapine cost 36,000/year. ◦ required contract with nurses that would take weekly blood tests ◦ subsequent costs ~ 12,000/year  now off patent ◦ reduced requirements by the FDA

30.  at least 7 new atypicals on the market – the most recent in 2003; one still in clinical trials  none are as effective as clozapine for treating tardive dyskinesias but none associated with the potentially lethal side effect  all expensive

31.  clozapine – Clozaril –  risperidone – Risperdal -  olanzapine – Zyprexa -  quetiapine – Seroquel -  ziprasidone – Geodon -  aripiprazole Abilify-

32.  good question – some say the drugs bind to D2 receptors but also to a certain type of 5HT receptors  some say these drugs do not bind quite as well to D2 receptors as the more traditional ones; but binds to other types of DA receptors  this is a huge step forward for treating schizophrenia

33.  From the basic research phase to completion of clinical trials.