Schizophrenia Flashcards
Eugen Bleuler is associated with what?
Terming the condition
What are the three categories of symptoms?
- Negative
- Cognitive
- Positive
Name the three types of positive symptoms
Hallucinations, delusions and thought disorders
How are negative symptoms defined?
Absence of normal behaviours
Give 2 examples of negative symptoms
Speech poverty, anhedonia, flattened emotional response, lack of initiative, persistence, social withdrawal
What cognitive symptoms are there?
Lower performance on IQ tests, planning and info processing deficits, working mem deficits, sensory-motor gating and anti-saccade task deficits, poor oculomotor function
What area of the frontal lobe specifically causes dysfunction?
Dorso-lateral PFC
What are the 2 tests that patients are slower at?
Stroop test and wisconsin card sort task
What are sensory motor gating deficits?
Difficulty screening out irrelevant stimuli
The event related potential that occurs approx 50 ms after the presentation of a stimulus is called what?
P50 wave
In the P50 signal task what % of the wave is diminished to the second click in healthy vs schiz ppts?
H = 80%, S = no change
What type of eye movements do patients show in the oculomotor task?
Catch up saccades
Who found that ventricle size of patients was more than twice as big as that of normal control subjects?
Weinburger and Wyatt, 82
There was less grey matter in what three brain regions? (82- Weinburger and Wyatt study)
Temporal, frontal and hippocampus
What gene is involved in the regulation of neurogenesis, neuronal migration, postsynaptic density and mitochondria function?
DISC1 gene
The presence of the DISC1 gene increases the chance o schizophrenia by a factor of what?
50
The DISC1 gene also increases the incidence of 2 other conditions, what are these?
Bipolar and autism
How does paternal age affect incidence rates?
After puberty they rapidly dividing (every 16 days), mutations in the spermatocytes which are the cells that produce sperm
What is a dichorionic MZ twin?
When the blastocyst division occurs before day 4 of development
What is the physical difference between di and monochorionic twins?
Di do not share a placenta
David and Phelps found the concordance rate for di versus monochorionic twins was what %?
D = 32%
M = 60%
What are examples of early events that cause schiz in the early model?
Infections, nutritional deficiencies
What early evidence suggests deviations in brain development? (Walker et al)
Children with schiz showed more negative affect in their facial expressions, and more abnormal movements
What study did Schiffman et al 2004 do?
Videotaped children eating lunch, blind raters found that the children who later developed schizophrenia displayed less sociability and less psychomotor function
Name the three models of schiz
Early model, late development model and two-hit model
What neurotransmitter hypothesis explains schiz?
Dopamine hypothesis
Overactivity in what area causes the positive symptoms and underactivity in what area causes the negative and cognitive symptoms?
Mesolimbic and mesocoritcal
What do these drugs: amphetamines, cocaine, methylphenidate and L-DOPA show about the DA hypothesis?
They are all dopamine agonists, and they all produce symptoms that resemble the positive symptoms of schiz
What type of drugs block dopamine receptors and alleviate symptoms?
Antipsychotics
Who discovered the drug chlorpromazine as the first antipsychotic?
Henri Laborit
What type of DA receptors do these antagonists block?
D2 type family
If a drug has low affinity what does this mean?
It binds loosly to the receptor and therefore a higher dose is needed
What radioactive tracer is used in SPECT studies?
Iodobenzamine (IBZM)
What is a reversible ligand?
It will compete with DA for binding to that receptor
What did Dargham et al, 1998 measure in their study?
Dopamine displacement after treatment with amphetamines
The study showed that patients with schiz had higher levels of displacement. What does this mean in terms of dopamine?
That they were releasing more dopamine in response to amphetamine compared to controls
The study also showed that higher displacement correlated with what type of symptoms?
Positive symptoms
Long-term treatment with typical antipsychotic drugs leads to what sort of symptoms?
Those resembling Parkinsons - slowness in movement, lack of facial expression and general weakness
What happens to patients with tardive dyskinesia?
They are unable to stop moving
Name 2 differences between A-typical and typical antiphsychotics.
- A-typ improves both positive and negative symptoms
- A-typ have lower affinity and therefore don’t produce the parkinsonian side-effects
Name the first a-typical antipsychotic
Clozapine
Give positives and negatives of clozapine
P = reduces suicide rate
N = side neffects such as weight gain, sedation, tachycardia
What role do NMDA receptors have during early development?
Neural migration, survival, pruning, plasticity and apoptosis
What is the glutamate hypo-functioning hypothesis and what does it explain?
NMDA hypofunction on GABA-ergic interneurons in the PFC
Explains treatment resistant symptoms, why the onset is early adulthood and why the disorder is associated with structural change
Blocking the NMDA receptor has what affect?
Leads to the excessive release of glutamate
PCP and ketamine are examples of what type of drug?
NMDA antagonists
What do glutamate agonists do to symptoms of schiz?
Improves both positive and negative symptoms
Describe the task used in the Jentsch 1997 study
Monkeys were given PCP for 2 weeks and tested a week later on a task that involved reaching around a barrier for a piece of food
What does it mean if an NMDA receptor is hypoactive
The activity of the NMDA receptor is inhibited
What were the results of the Jentsch 1997 study?
Performance on the task depends on the function of the PFC, whether animals had lesions here, and control monkeys performed well but depended on PCP treatment
What causes the lack of inhibition of glutamate?
Hypofunctioning NMDA receptors at the GABA ergic interneuron in the prefrontal cortex, disinhibits the GABA ergic interneuron, which leads to increased glutamate release
What does increased glutamate lead to?
Over excitation into the mesolimbic system (VTA) which causes the release of dopamine
In the mesocortical system, how are dopamine levels low?
Increased glutamate caused by the hypo-functioning NMDA receptor, leads to high excitation at the additional GABA receptor in the PFC, which leads to high levels of inhibition and lower dopamine release
What is the role of microglial cells and what is different in patients?
The brains immune cells and they are hyperactive
What have animal studies shown about pro-inflammatory agents and schiz symptoms?
They increase symptoms
GWAS studies showed what genes are involved in the heritability of schiz?
DRD2, GLU receptor subunits
Where is the most significant association found and what region of genes does it include?
Chromosome 6 which includes a region of genes involved in acquired immunity - MHC
What does it mean if a microglia is amoeboid?
It has swollen up and is releasing chemicals
What other role does microglia have in early brain development?
Neuronal cell death and survival, synaptogenesis and pruning
How might early infection lead to schiz according to the microglial theory?
Early infection primes the microglia, which may interact with the developing cells in the nervous system, leading to rearrangements of the sympathetic circuitry
How does oestrogen play a protective role?
17B-estradiol is the mos potent form, the second peak of onset for women may be linked to the decrease in oestrogen following menopause
Name the environmental factors that are related to spread of disease and infection
Season of birth, population density and viral epidemics
What are the other environmental factors that increase schiz?
Vitamin D deficiencies, substance abuse and prenatal malnutrition
What factors would affect vitamin D levels?
Urban areas, those in more extreme latitudes, and those with more melanin
