Lecture 10- Schizophrenia Flashcards
Schizophrenia affects
1% of the worlds population
What is schizophrenia known as
A break from reality
Three categories of symptoms
- Positive
- Negative
- Cognitive
Symptom onset is usually in
Early adulthood but can happen earlier or later
Which type of symptoms are the first to emerge
- Negative
- Then cognitive
- Then positive
What do positive symptoms include
- Thought disorders
- Delusions
- Hallucinations
What are positive symptoms
Extra to life (hallucinations)
What do thought disorders contain
- Disorganised, irrational thinking
- Difficulty arranging thoughts logically
- Jump from topic to topic
- Sometimes choose meaningless or rhyming words
Types of delusions
- Persecution, false beliefs of threats
- Grandeur, power or importance
- Control, related to persecution, being controlled by others
Most common type of hallucinations
-Auditory
What are olfactory hallucinations
- Think they experience something others can’t detect
- Contribute to the delusion that others are trying to kill them
Why are they described as negative symptoms
Absence of normal behaviours
Examples of negative symptoms
- Poverty of speech
- Social withdrawal
- Lack of initiative
- Persistence
- Flattened emotional response
Cognitive symptoms include
- Difficulty in sustaining attention
- Poor abstract thinking
- Poor problem solving
- Low psychomotor speed
All neurocognitive deficits are associated with
Frontal lobe hypofunction
Weinberger (1988) suggested that the negative symptoms of schiz are caused primarily by
Hypofrontality (decreased activity)
What’s the stroop task
- 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
What’s the Wisconsin card sort task
- Sorting cards and trying to work out the rule
- Normally there is an increase in blood flow to dIPFC
- Schizophrenia reduced blood flow there
What are sensory motor gating deficits
- Difficulties screening out irrelevant stimuli
- Schizophrenia seem to not be good at screening
What’s the P50 signal in event related potentials
- 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
Difference in Pre-Pulse Inhibition between normal and schizophrenia
- Weak stimulus precedes a startle compared to just startle
- Normal response inhibits startle if there’s a initial weak stimulus
- Schizophrenia no change
What’s smooth pursuit
Tracking a moving stimulus
How do normal and schizophrenia differ in smooth persuit
Eye movements not as smooth, distracted and catching up with stimulus
Ventricle sizes difference
- Schizophrenia twice as big
- Reduced brain volume, less grey matter
- Reduced size in temporal, frontal lobes and hippocampus
While schizophrenia is heritable
It is not due to a single dominant or recessive gene
One rare mutation involves the gene
DISC1
What is DISC1 involved in
- Regulation of Neurogenesis
- Neuronal migration
- Postsynaptic density in excitatory neurons
- Mitochondria function
DISC1 presence increases chance of schizophrenia by a factor of
50
Children of what fathers are more likely to develop schizophrenia
- Older fathers
- Likely due to mutations in spermatocytes
Percentage of developing schizophrenia if both parents are schizophrenic
46%
Percentage of developing schizophrenia if MZ twin is schizophrenic
48%
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
‘Early’ neurodevelopmemtal model
- Events in early life cause deviations from norm
- Infections, nutritional deficiency support this theory
Evidence suggesting abnormal brain development
-Blind raters found that children with later schizophrenia development were less social
Late neurodevelopmental model
Schizophrenia may result from an abnormality when synaptic pruning occurs
Two hit model
- Early developmental insults may lead to dysfunction of specific neural networks
- Adolescence has excessive synaptic pruning
How does cannabis use relate to schizophrenia
In adolescence it can cause 6x risk
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
What does the DA pathway look like in positive symptoms
-Excess levels of DA in the mesolymbic pathway
What does the DA pathway look like in negative, cognitive symptoms
Lower levels of DA in the prefrontal cortex
DA agonist produce symptoms that resemble
Positive symptoms of schizophrenia
Drugs that mimic positive DA symptoms
- Amphetamine
- Cocaine
- L-DOPA
- Methylphenidate
Positive symptoms can be alleviated with
- Antipsychotic drugs
- CPZ, DA antagonist
Typical antipsychotics target
Block D2 receptors
What percentage of patients do not respond to typical antipsychotics
20-30%
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
Atypical antipsychotics work in
Treatment resistant patients
Atypical antipsychotics do not have
- Parkinson’s side effects
- Have a lower affinity for the D2 receptors
- Improve negative and positive symptoms of schizophrenia
Clozapine
- First atypical antipsychotic drug
- Lower affinity for D2, higher affinity for other DA receptors
- Not widely used
- Reduces suicide rates
Problem with DA hypothesis
- Only explains part of schizophrenia
- Atypical antipsychotics are better yet they target dopamine less
Nearly 50% of the neurons in the brain are believed to use
Glutamate as their neurotransmitter
NDMA receptors are connected to
Schizophrenia when NMDA hypofunction
NMDA receptors are a critical component of
Developmental processes
E.g. neural plasticity, neural pruning of cortical connections
Glutamate agonist seem to improve
Both positive and negative symptoms of schizophrenia
Negative and cognitive symptoms produced by ketamine and PCP caused by
Decrease in the metabolic activity of the frontal lobes
Positive symptoms associated with NMDA receptors that
Are hypofunctional in the prefrontal cortex
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
Disinhibited glutamate results in
Higher levels of dopamine
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
People who are at risk of schizophrenia’s brain immune cells are
Hyperactive
Antibiotics that reduce microglial activation cause
Symptoms to be reversed
Most significant association of chromosome with schizophrenia is
Chromosome 6 with a region of the genes involved in acquired immunity
Microglia
- Survey the brain for pathogens
- Identification of a threat causes them to become activated
- Involved in neuronal cell death, synaptic pruning
Microglial activation is not
Instantaneous
In women there is
A 2nd peak onset of schizophrenia at age 45-50 yrs (menopause)
