Week 11 - psychotic disorders Flashcards
What are some clinical manifestations of schizophrenia?
Major disturbances in thought, emotion and behaviour
- Disordered thinking
- Lack of emotional expressiveness
- Disturbances in movement or behaviour
Can disrupt interpersonal relationships, diminish the capacity to work or live independently
What is the lifetime prevalence of schizophrenia?
1%
When does onset of schizophrenia typically occur?
Late adolescence or early adulthood
What are the positive symptoms of schizophrenia?
Delusions
Hallucinations
What are the negative symptoms of schizophrenia?
Avolition
Alogia
Anhedonia
Blunted affect
Asociality
What are the disorganised symptoms of schizophrenia?
disorganised behaviour
disorganised speech
What are the different types of delusions?
Persecutory
Thought insertion
Thought broadcasting
Outside control
Grandiose delusions
Ideas of reference
What are the different types of hallucinations?
Auditory
Visual
Hearing voices
What are the two domains of the negative symptoms of schizophrenia?
Experience domain
- Motivation
- Emotional experience
- Sociality
Expression domain
- Expression of emotion
- Vocalisations
What is thought to cause the positive symptoms of schizophrenia?
An excess of dopamine in the mesolimbic pathway, although the reasons for this increase are not known
What may be therapeutic to the positive symptoms of schizophrenia?
Decreasing the dopamine in the mesolimbic pathway
What is thought to cause the negative and cognitive symptoms of schizophrenia?
A shortage of dopamine in the mesocortical pathway
What may be therapeutic for the negative and cortical symptoms of schizophrenia?
Increasing dopamine in the mesocortical pathway
What happens when you treat schizophrenia with a D2 antagonist antipsychotic?
Can successfully treat positive symptoms by reducing dopamine signalling in the mesolimbic pathway
However, the dopamine antagonist also reduces signalling in the mesocortical pathway meaning that the negative and cognitive symptoms are not addressed, and in some cases, can be worsened
What happens when you treat schizophrenia with an atypical D2 partial agnoist antipsychotic?
Works to reduce the excess dopamine in the mesolimbic pathway, treating the positive symptoms
Simultaneously, within the mesocortical pathway a dopamine partial agonist will act to enhance dopamine signalling, meaning that the negative and cognitive symptoms of schizophrenia could be improved as well
What is the glutamate hypothesis?
Glutamate is the predominant ‘go’ neurotransmitter in the brain
There are many lines of evidence implicating glutamate NMDA receptors in schizophrenia
What does the evidence implicate regarding glutamate NMDA receptors in schizophrenia?
Post mortem changes in NMDA receptors in the brains of patients with schizophrenia
NMDA-receptor antagonists can cause psychotic symptoms in humans
Some glutamatergic drugs have shown promise in treating schizophrenia
Describe the interactions between glutamate and dopaminergic pathways.
Reduced NMDA receptor availability/functioning on GABAergic interneurons >
Disinhibition of glutamatergic projections onto midbrain dopamine neurons >
Increased glutamate release >
Increase activation of dopaminergic neurons
What is ventricular enlargement correlated with?
Poor performance on cognitive tests
Poor premorbid adjustment
Poor response to treatment
Describe schizophrenia vs treatment-resistance schizophrenia (TRS)
TRS may represent a distinct pathophysiological entity
What differences have brain imaging techniques highlighted regarding the brain structures of TRS and treatment-responsive schizophrenia?
Widespread grey matter volume reductions in several lobes of the brain
How does brain connectivity differ for patients with treatment-resistant schizophrenia?
Reduced connectivity in certain key brain regions and a reduced total density of dopaminergic synapses, compared to treatment-responsive schizophrenia and the control population
When does psychosis emerge?
Late adolescence or early adulthood with a peak between the ages of 18 and 25, when the prefrontal cortex is still developing
In the neurodevelopmental model of schizophrenia, what is observed with longitudinal neuroimaging?
A progressive reduction of grey-matter volume with age
The combined effects of pruning of the neuronal arbour and myelin deposition are thought to account for this
What does normal cortical development involve?
Proliferation
Migration of cells
Dendritic aborisation
Myelination
The first two processes occurring mostly during prenatal life and the latter two continuing through the first two post-natal decades
What is the evidence that the immune system is linked to the pathology of schizophrenia?
Elevated cytokines and microglial activation
How has PET imaging been used?
To examine immune system activity in patients with schizophrenia
In comparison of 16 patients with schizophrenia and 16 controls, what differences were found in oropharynx flora?
Patients with schizophrenia were dominated by a greater number of microbiome species
Patients with schizophrenia had greater abundance of lactic acid bacteria
There were difference in the metabolic pathways controlling glutamate and B12 transport (increase in schizophrenia) and carbohydrate and lipid metabolism (decreased in schizophrenia
What have epidemiological studies and twin studies identified about environmental factors and schizophrenia?
Prenatal exposure to viral infections
Poor pre-natal nutrition
Adverse obstetric events
Cannabis smoking during adolescence
What have numerous studies found about the genetic factors of schizophrenia?
Developing schizophrenia is greater in the relatives of patients with schizophrenia
Susceptibility genes may result in an increased risk of schizophrenia
