Lecture 10- Schizophrenia Flashcards
1
Q
Schizophrenia affects
A
1% of the worlds population
2
Q
What is schizophrenia known as
A
A break from reality
3
Q
Three categories of symptoms
A
- Positive
- Negative
- Cognitive
4
Q
Symptom onset is usually in
A
Early adulthood but can happen earlier or later
5
Q
Which type of symptoms are the first to emerge
A
- Negative
- Then cognitive
- Then positive
6
Q
What do positive symptoms include
A
- Thought disorders
- Delusions
- Hallucinations
7
Q
What are positive symptoms
A
Extra to life (hallucinations)
8
Q
What do thought disorders contain
A
- Disorganised, irrational thinking
- Difficulty arranging thoughts logically
- Jump from topic to topic
- Sometimes choose meaningless or rhyming words
9
Q
Types of delusions
A
- Persecution, false beliefs of threats
- Grandeur, power or importance
- Control, related to persecution, being controlled by others
10
Q
Most common type of hallucinations
A
-Auditory
11
Q
What are olfactory hallucinations
A
- Think they experience something others can’t detect
- Contribute to the delusion that others are trying to kill them
12
Q
Why are they described as negative symptoms
A
Absence of normal behaviours
13
Q
Examples of negative symptoms
A
- Poverty of speech
- Social withdrawal
- Lack of initiative
- Persistence
- Flattened emotional response
14
Q
Cognitive symptoms include
A
- Difficulty in sustaining attention
- Poor abstract thinking
- Poor problem solving
- Low psychomotor speed
15
Q
All neurocognitive deficits are associated with
A
Frontal lobe hypofunction
16
Q
Weinberger (1988) suggested that the negative symptoms of schiz are caused primarily by
A
Hypofrontality (decreased activity)
17
Q
What’s the stroop task
A
- Incongruent task:
- Trying to name the colour of the ink not the word (which would be a colour)
- Schizophrenia patients are slower and less accurate
18
Q
What’s the Wisconsin card sort task
A
- Sorting cards and trying to work out the rule
- Normally there is an increase in blood flow to dIPFC
- Schizophrenia reduced blood flow there
19
Q
What are sensory motor gating deficits
A
- Difficulties screening out irrelevant stimuli
- Schizophrenia seem to not be good at screening
20
Q
What’s the P50 signal in event related potentials
A
- 2 auditory stimuli 500ms apart
- Healthy people have a P50 wave on the 2nd click which is 80% diminished
- Schizophrenia there is no change in response to 2nd click
21
Q
Difference in Pre-Pulse Inhibition between normal and schizophrenia
A
- Weak stimulus precedes a startle compared to just startle
- Normal response inhibits startle if there’s a initial weak stimulus
- Schizophrenia no change
22
Q
What’s smooth pursuit
A
Tracking a moving stimulus
23
Q
How do normal and schizophrenia differ in smooth persuit
A
Eye movements not as smooth, distracted and catching up with stimulus
24
Q
Ventricle sizes difference
A
- Schizophrenia twice as big
- Reduced brain volume, less grey matter
- Reduced size in temporal, frontal lobes and hippocampus
25
While schizophrenia is heritable
It is not due to a single dominant or recessive gene
26
One rare mutation involves the gene
DISC1
27
What is DISC1 involved in
- Regulation of Neurogenesis
- Neuronal migration
- Postsynaptic density in excitatory neurons
- Mitochondria function
28
DISC1 presence increases chance of schizophrenia by a factor of
50
29
Children of what fathers are more likely to develop schizophrenia
- Older fathers
| - Likely due to mutations in spermatocytes
30
Percentage of developing schizophrenia if both parents are schizophrenic
46%
31
Percentage of developing schizophrenia if MZ twin is schizophrenic
48%
32
What biological reason might there be for differences in MZ twins
- two organisms form their own placenta before day 4
- if after day 4 organisms become monochorionic, one placenta
- monochoronic twins found 60% concordance rate
33
‘Early’ neurodevelopmemtal model
- Events in early life cause deviations from norm
| - Infections, nutritional deficiency support this theory
34
Evidence suggesting abnormal brain development
-Blind raters found that children with later schizophrenia development were less social
35
Late neurodevelopmental model
Schizophrenia may result from an abnormality when synaptic pruning occurs
36
Two hit model
- Early developmental insults may lead to dysfunction of specific neural networks
- Adolescence has excessive synaptic pruning
37
How does cannabis use relate to schizophrenia
In adolescence it can cause 6x risk
38
Dopamine (DA) hypothesis
- Schizophrenia is due to abnormalities in DA functioning
- Overactivity of DA, Results in positive symptoms
- Underactivity in DA, results in negative and cognitive symptoms
39
What does the DA pathway look like in positive symptoms
-Excess levels of DA in the mesolymbic pathway
40
What does the DA pathway look like in negative, cognitive symptoms
Lower levels of DA in the prefrontal cortex
41
DA agonist produce symptoms that resemble
Positive symptoms of schizophrenia
42
Drugs that mimic positive DA symptoms
- Amphetamine
- Cocaine
- L-DOPA
- Methylphenidate
43
Positive symptoms can be alleviated with
- Antipsychotic drugs
| - CPZ, DA antagonist
44
Typical antipsychotics target
Block D2 receptors
45
What percentage of patients do not respond to typical antipsychotics
20-30%
46
Long term treatment of typical antipsychotics leads to symptoms resembling
- Parkinson’s disease
- Lack of facial expression, slowness in movement
- Help with positive not really negative symptoms
47
Atypical antipsychotics work in
Treatment resistant patients
48
Atypical antipsychotics do not have
- Parkinson’s side effects
- Have a lower affinity for the D2 receptors
- Improve negative and positive symptoms of schizophrenia
49
Clozapine
- First atypical antipsychotic drug
- Lower affinity for D2, higher affinity for other DA receptors
- Not widely used
- Reduces suicide rates
50
Problem with DA hypothesis
- Only explains part of schizophrenia
| - Atypical antipsychotics are better yet they target dopamine less
51
Nearly 50% of the neurons in the brain are believed to use
Glutamate as their neurotransmitter
52
NDMA receptors are connected to
Schizophrenia when NMDA hypofunction
53
NMDA receptors are a critical component of
Developmental processes
| E.g. neural plasticity, neural pruning of cortical connections
54
Glutamate agonist seem to improve
Both positive and negative symptoms of schizophrenia
55
Negative and cognitive symptoms produced by ketamine and PCP caused by
Decrease in the metabolic activity of the frontal lobes
56
Positive symptoms associated with NMDA receptors that
Are hypofunctional in the prefrontal cortex
57
Glutamate hypothesis in relation to the dopamine hypothesis with positive symptoms
In healthy brains GABA neuron will inhibit the glutamatergic neuron, allowing normal level of dopamine release
58
Disinhibited glutamate results in
Higher levels of dopamine
59
Hypo-functioning NMDA Receptors theory accounts for
Both excess DA release in the mesolymbic DA system as well as reduced release of DA in the prefrontal cortex
60
People who are at risk of schizophrenia’s brain immune cells are
Hyperactive
61
Antibiotics that reduce microglial activation cause
Symptoms to be reversed
62
Most significant association of chromosome with schizophrenia is
Chromosome 6 with a region of the genes involved in acquired immunity
63
Microglia
- Survey the brain for pathogens
- Identification of a threat causes them to become activated
- Involved in neuronal cell death, synaptic pruning
64
Microglial activation is not
Instantaneous
65
In women there is
A 2nd peak onset of schizophrenia at age 45-50 yrs (menopause)
