Week 14 - Biology and treatment of psychosis Flashcards
What are the lateral ventricles and what do they contain?
They are spaces in the brain that are filled with CSF
Where is CSF produced and what is its function?
- Produced by the choroid plexus
- Provides physical protection and physiological maintenance to the brain
What area of the brain shows a difference in size in people with schizophrenia?
The lateral ventricles
What type of brain drug could explain the larger lateral ventricles seen in some individuals with schizophrenia?
It’s possible that the amount of brain tissue surrounding the lateral ventricles has decreased - the ‘shrinkage’ would then allow more space for the ventricles to fill with CSF
What is the name of the top branch of the lateral ventricles?
The anterior horn
What is the name for the bottom branch of the lateral ventricles?
The inferior or temporal horn
What change in the ventricles has been noted in some individuals with SSDs?
They are found to be enlarged
What information does the amygdala process?
Information regarding emotions, learning and memory
What change in the amygdala has been found in some individuals with SSDs?
It has been found to be overactive
What is the hippocampus important for?
Learning and memory
What changes are noted in the hippocampus in some individuals with SSDs?
It may be reduced in size
What type of projcetions does the hippocampus send to the nucleus accumbens?
Glutaminergic projections
What does the nucleus accumbens play an important role in?
Reward-related learning
What does the ventral palladium play a critical role in?
Processing and execution of motivated behaviour
What type are many of the neurons in the ventral palladium?
GABAergic
What is meant by the term projection neuron?
A neuron whose axon extends from one region or structure of the CNS to another (sometimes distant) region or structure
What are medium spiny neurons (MSNs)?
A type of GABAergic inhibitory projection neuron
What type of interneurons and projection neurons are in the amygdala?
- GABAergic interneurons
- Glutamatergic projection neurons
What effect do the GABAergic interneurons in the amygdala have?
They modulate (decrease) glutamatergic projection neuron activity
In SSDs, what is thought to be the the effect that glutamatergic projections from the PFC have on the activity of the GABAergic interneurons of the amygdala?
They might fail to properly modulate (increase)
If GABAergic interneurons in the amygdala fail to modulate the glutamatergic projection neurons, what will happen to the glutamatergic projection neurons of the amygdala?
They will become overactive
What can happen to the projection from the amygdala to the hippocampus in people with SSDs?
It cam become overactive
If the projection from the amygdala to the hippocampus becomes overactive, what can the resulting effect be?
It will contribute to damage of GABAergic interneurons in the hippocampus
What is the effect on the hippocampus if its GABAergic interneurons are damaged?
It can lead to a reduction in the size of the hippocampus
If GABAergic interneurons in the hippocampus are damaged, what effect can this have on the nucleus accumbens?
The excitability of glutamatergic projections to the NAc cannot be controlled
If excitability of glutamatergic projections to the NAc cannot be controlled, what is the effect on the nucleus accumbens?
It leads to hyperactivity of the NAc
What is the name of the GABAergic neurons in the nucleus accumbens?
Medium spiny neurons (MSNs)
Is the GABAergic pathway of medium spiny neurons which projects from the nucleus accumbens to the ventral palladium inhibitory or excitatory?
Inhibitory
In SSDs, is the nucleus accumbens likely to be hypo- or hyperactive?
Hyperactive
Which type of neurons are found in the ventral tegmental area?
Dopamine neurons?
Where do some of the dopaminergic neurons of the ventral tegmental area project to?
The nucleus accumbens
Via which pathway do some of the dopaminergic neurons of the ventral tegmental area project to the ventral tegmental area?
Via the mesolimbic dopamine pathway
Via which pathway do some of the dopaminergic neurons of the ventral tegmental area project to the prefrontal cortex?
The mesocortical dopamine pathway
In SSDs, hyperactivity of the hippocampus could lead to what type of activity in the mesolimbic and mesocortical dopaminergic pathways?
Enhanced
Which structures are found to be enlarged in some people with SSDs?
The lateral ventricles
Which brain structure is reduced in size in some people with SSDs?
The hippocampus
Which neurotransmitter pathway connects the amygdala with the hippocampus?
Glutamatergic
Which neurotransmitter is released by the medium spiny neurons located in the nucleus accumbens which project into the ventral palladium?
GABA
In studies of twins, if one twin has SSD-associated reduction in the size of their hippocampus, is it likely that the other twin will also have a reduction in the volume of their hippocampus?
No
In people with an SSD, what is the effect on the activity level of neurons in their hippocampus?
Activity levels are higher, especially during hallucinations
What effect on the density of GABAergic interneurons in the hippocampus has been noted in some people with schizophrenia?
A mared reduction in the density
What is meant by the term disinhibited?
When an excitatory neuron becomes more active because it is no longer inhibited by another neuron
In people with SSDs, what are three effects of dysregulated hippocampal function?
- As the hippocampus is vital to the formation of new memories, people with SSDs may have difficulty in remembering words which are presented to them
- Spatial memory is processed in the hippocampus and so also disrupted in those with SSDs
- Individuals with SSDs are slower at becoming familiar with, or habituated to, stimuli that are repeatedly shown to them
What is meant by the term habituation?
The gradual decrease in response to a stimulus that is constantly present or frequently encountered
What is the hypothalmic-pituitary-adrenal axis (HPA axis)?
A pathway connecting the hypothalamus, pituitary gland and adrenal glands
What activates the HPA axis (hypothalamic-pituitary-adrenal axis)?
Stress
If stress activates the HPA axis (hypothalmic-pituitary-adrenal axis) what hormone is released into the body?
Cortisol
What is a potential negative consequence of high cortisol levels?
Damage to the hippocampus
What type of projections does the amygdala send to the hippocampus?
Glutamatergic projections
In animal experiments, what consequence was found in response to overactivity of the glutamatergic projections from the amygdala to the hippocampus?
Damage to GABAergic interneurons in the hippocampus
Will the activity of glutamatergic projection neurons from the hippocampus be altered if GABAergic interneurons are damaged in this region?
Yes - the hippocampus may become overly excited because the GABAergic neurons can no longer inhibit the glutamatergic neurons
How may the brain help alleviate some of the damage to hippocampal GABAergic neurons caused by an overactive amygdala?
Certain areas of the PFC send glutamatergic axons to the amygdala which results in inhibition of parts of the amygdala
Is overactivity or underactivity of the hippocampus associated with psychosis?
Overactivity
If you can prevent damage to GABAergic interneurons of the hippocampus by decreasing glutamatergic input from the amygdala to the hippocampus, would this increase or decrease the excitation of the glutamatergic neurons that project from the hippocampus?
Decrease
Excitatory glutamatergic neurons of the hippocampus are thought to be over- or underactive in people with an SSD?
Overactive
Excessive excitation of the glutamatergic neurons of the hippocampus may have what indirect effect?
Exaggerated dopamine neurotransmission in the brain
Which region in the brain has cell bodies of dopaminergic neurons which send projections to the nucleus accumbens and the prefrontal cortex?
Ventral tegmental area
As well as receiving dopamine input from the ventral tegmental area, what other input does the nucleus accumbens receive?
Glutamate input from the hippocampus
Would glutamate release from the hippocampus increase or inhibit the activity of neurons in the nucleus accumbens?
Increase, as glutamate is an excitatory neurotransmitter
What is the name for the GABAergic neurons in the nucleus accumbens which receive dopamine and glutamate input?
Medium spiny neurons
Where do the medium spiny neurons in the nucleus accumbens project to?
The ventral pallidum
Would the GABAergic neurons of the nucleus accumbens known as medium spiny neurons excite or inhibit the neurons of the ventral pallidum?
Inhibit, as GABA is an inhibitory neurotransmitter
If active neurons of the ventral pallidum are active and thus inhibiting the ventral tegmental area, what impact might there be on dopamine release in the nucleus accumbens and prefrontal cortex?
Inhibiting the dopamine neurons may reduce dopamine release in the target regions
In SSDs the hippocampus may be overactive. How might this affect dopamine release in the nucleus accumbens and the prefrontal cortex?
If dopamine neurons in the ventral tegmental area are disinhibited they are more likely to be active and release dopamine in the nucleus accumbens and prefrontal cortex
In people with SSDs, what effect may amphetamine have?
As it increases dopamine neurotransmission, it may induce symptoms of psychosis
What and when was the first antipsychotic drug to be discovered?
- Chlorpromazine
- 1950s
What was chlorpromazine originally developed for?
To reduce pre-operative anxiety
How are D1 and D2 receptors similar?
They both metabotropic receptors that bind dopamine in the brain
How are D1 and D2 receptors different?
- D1 receptors are located on the postsynaptic membrane and are considered stimulatory
- D2 receptors are located on both the postsynaptic and presynaptic membranes and are considered inhibitory
How would a drug function if it is considered to be an agonist at D2 receptors?
The drug would bind to the receptors and prevent dopamine from binding and having its usual physiological effects
What are first-generation antipsychotics most effective at doing?
Eliminating (or at least reducing) positive symptoms of psychosis such as hallucinations and delusions
What are second-generation antipsychotics most effective at doing?
They may decrease positive, negative and cognitive symptoms of SSDs
What was the original second-line antipsychotic drug?
Clozapine
Is clozapine or chlorpromazine more effective at reducing aspects of psychosis?
Clozapine
As well as targetting D2 receptors, how else does clozapine work?
It can decrease dopamine function in mesolimbic areas such as the nucleus accumbens, while increasing dopamine transmisison in the prefrontal cortex
What effect may clozapine have on D1 receptors in the prefrontal cortex?
It may be an agonist
What is the effect on the neuron when dopamine binds to D1 receptors?
It has a stimulatory effect on the neuron
What theory underlies CBT?
It focuses on a person’s goals and what is currently impacting their life and considers that how a person thinks can influence feelings and behaviour
In individuals with schizophrenia, what effect may exercise have in the brain?
It may increase hippocampal size
