PSYC 415 -- Dr. King -- Study Points for schizophrenia

I. Positive vs. Negative Symptoms
   A. positive symptoms - hallucinations, delusions, thought disorder, mannerisms
   B. negative symptoms - flattened affect, apathy, anhedonia, poverty of speech,
                          stupor, catatonia, social withdrawal, deterioration
II. Cognitive Symptoms - difficulty in sustaining attention, low psychomotor speed,
                         learning and memory deficits, poor abstract thinking,
                         poor problem solving
III. Statistics
   A. 1% of people will be diagnosed at some time during their lives (lifetime risk)
   B. about 100,000 newly diagnosed cases per year (incidnece)
   C. 2.2 million people are currently diagnosed in U.S. (prevalence)
IV. First Diagnosis
   A. most commonly during adolescence
   B. a little earlier in men than women
   C. tends to be a little more severe in men as well
V. Course
   A. negative symptoms first (prodromal)
   B. followed by cognitive symptoms
   C. followed sometimes years later by positive symptoms
VI. Rule of Quarters
   A. about 1/4 of people diagnosed will improve to the point where they are
      considered cured (or "in remission")
   B. about 1/4 will show some improvement
   C. about 1/4 will show no improvement
   D. about 1/4 will continue to deteriorate (esp. likely in those with
      prominent negative symptoms
VII. Schizophrenia and Public Health - a very serious public health problem, esp.
     because it tends to be chronic
VIII. Heritability
   A. twin studies - MZ twins are more likely to be concordant (50%)
      than DZ twins (<20%)
   B. adoption studies - more likely correlated with biological than adoptive 
      family
   C. morbid risk - Gottesman & Bertelsen (1989); be sure you understand this
IX. Congenital Factors
   A. birth complications
   B. maternal viral infections
X. Methylation Theory - no longer really considered seriously
XI. Dopamine Theory
   A. drugs that alleviate symptoms of schizophrenia are DA receptor blockers
      1. chlorpromazine (Thorazine) - introduced in 1956
      2. dozens of others introduced since
      3. they are not a cure for schizophrenia (just like insulin isn't a cure
         for diabetes or aspirin for a headache)
      4. side effects - Parkinsonism and tardive dyskinesia
   B. amphetamine-induced stereotypy
   C. atypical antipsychotics - e.g., clozapine
   D. dopamine pathways
      1. nigrostriatal system - substantia nigra to basal ganglia
      2. mesolimbic system - ventral tegmental area to nucleus accumbens, 
         amygdala, and prefrontal cortex
   E. potency of drugs is strongly correlated with drug's ability to block
      DA receptors (Snyder et al., 1978)
   F. more suggestions that DA is involved
      1. amphetamine psychosis - LSD does not produce psychosis
      2. DA receptor studies - at autopsy and by PET scanning
      3. functional imaging studies
   G. Dopamine Theory: Problems
      1. about 1/3 of patients who get DA receptors blockers are nonresponders
      2. onset of drug response is delayed by 2-3 weeks
      3. tardive dyskinesia is not accompanied by tardive schizophrenia - or is it?
XII. Schizophrenia as a Neurological Disorder
   A. soft neurological signs - strange eye movements, unusual reflexes, etc.
   B. general brain atrophy shows up as enlarged ventricles
   C. loss of cortical gray matter
   D. cell loss and disorganization in the hippocampus
   E. hypofrontality - Wisconsin Card Sort Test
   F. possibility of a viral infection causing brain damage
      1. there are viral related psychoses
      2. but the evidence for a viral infection in schizophrenia is slim
      3. NO evidence that schizophrenia is in any way contagious
XII. Epidemiology
   A. seasonality effect - those born in late winter and early spring are
      slightly more likely to get it
   B. population density - living in a densely populated area increases risk
      about 3 time
   C. prenatal malnutrition
   D. prenatal maternal stress
   E. obstetric complication
XIII. The Emerging Story - abnormal brain development is strongly implicated
   A. esp. in the dorsolateral prefrontal cortex (DLPFCx)
      1. hypofrontality
      2. esp. important in development of negative symptoms
      3. working memory impairment - deficient activation of DLPFCx)
      4. associated with changes in DA activity in the nuc. accumbens
      5. PCP and ketamine
          a. decrease metabolic activity in frontal lobes
          b. chronic use can result in negative- and cognitive-like symptoms
          c. eventually positive symptoms as appear
XIV. So Here's What Happens
   A. a developmental brain disorder becomes esp. severe during adolescence
      and results in degeneration in the DLPFCx
   B. results in a loss of glutamine neurotransmission into the VTA
   C. decreased activation of DA neurons that project back to the frontal lobe
      and a decreased release of DA there - negative symptoms
   D. decreased activation of GABA interneurons
   E. which results in increased activity of DA neurons projecting to nuc.
      accumbens - positive symptoms
   F. clozapine, etc., increases DA activity in frontal cortex but decreases it
      in the nuc. accumbens
      1. partial agonist
      2. binds to receptors but activates them less than natural ligand (DA)
      3. alleviate both positive and negative symptoms