1. Neurological Disorders

2. Alzheimer's Disease chromosomes 1, 14, 19, and 21
general brain atrophy
neuronal degeneration
decreased cerebral metabolism
general decay of ACh system
beta-amyloid plaques
neurofibrillary tangles
Alzheimer's
Normal

3. Beta-Amyloid Plaques Beta-Amyloid Plaques Tau Filaments Pathology:
Interferes with Ca2+ regulation
Increases free radicals
Stimulates microglia aggregation
Increases inflammation

4. Neurofibrillary Tangles
Microtubules:
Provide structural support
Are pathways for:
Nutrients
Waste products
Neurotransmitters
Made of Tubulin
In Alzheimer’s Disease:
Excess Tau protein binds builds up
Tau binds with Tubulin and tangles the microtubules preventing them from properly functioning

5. Schizophrenia Onset can be slow or sudden Typically exists chronically
Affects ~1% of population
Diagnosis must have at least two symptoms for more that 1 month

6. Schizophrenia Symptoms
Positive Symptoms (abnormal states)
hallucinations (auditory, visual)
delusions (grandeur, persecution)
Negative Symptoms (insufficient functioning)
avolition (inability to initiate/persist in activities)
alogia (absence of speech)
anhedonia (inability to experience pleasure)
affective flattening (flat emotional response)
Disorganized Symptoms
inappropriate affect (laughing/crying at the wrong times)
disorganized speech (illogical, rambling, tangential)
disorganized behavior (catatonia, agitation/immobility)

7. Schizophreni Genetic Risk by Relatedness
The Evidence:
Family History
Twin Studies
monozygotic (50%)
same handed (92%)
dizygotic (15%)
both are carriers
Adopted Children
more like bioparents
Single Gene?
Probably not

8. Brain Structure Abnormalities Increased Lateral Ventricles

9. Brain Structure Abnormalities Reduced Hippocampus and Amygdala
Affected
Affected
Normal

10. Schizophrenia Abnormality Hippocampal Pyramidal Cell Disorganization

11. Neurobehavioral Hypothesis
Maternal/Fetal Evidence:
extensive maternal bleeding
prolonged labor
delivery complications
low birth weight
low head circumference
body length:body weight
multiparity
Anectodal Evidence
Dutch births during WWII
Season of birth effect
higher for winter pregnancies
parallel with virus exposure

12. Dopamine Hypothesis of Schizophrenia
Abnormal levels of Dopamine lead to the schizophrenic symptoms
1. Amphetamine Psychosis
Chronic users develop schizophrenic symptoms
paranoia, delusions of persecution, auditory hallucinations
Amphetamine exacerbates schizophrenic symptoms
Amphetamines promote the release of catelcholamines
particularly dopamine
2. Antipsychotic Drugs
chlorapromazine is a dopamine antagonist and antipsychotic
block specifically D2 and D4 receptors in the limbic system
effectiveness is related to magnitude of blockade
3. Parkinson’s Disease
some patients receiving L-dopa become psychotic
some schizophrenic patients on antipsychotics develop Parkinson’s symptoms

13. Correlation between Antipsychotic Drug Binding to D2 Receptors and Clinical Effectiveness
Greater Clinical Effectiveness
Chlorpromazine (Thorazine) first drug to find positive effects
Strong Correlation with DA 2 receptor blockers
Psychopharmacology2e-Fig R.jpg
Greater Binding to D2 receptors