Schizophrenia (Yvonne Mbaki) Flashcards
Men are more susceptible to schizophrenia than women, what is one theory as to why?
Oestrogen has a regulatory role in dopamine receptor sensitivity
When does schizophrenia typically present?
In late adolescence or early adulthood, (acute onset over 2-3 weeks)
What are some of the environmental factors that can increase the risk of development?
Urban areas, men are more prone
Countries further from the equator with a colder climate, more common cases
Perinatal complications; severe malnutrition, exposure to stressful events, birth complications, altered brain development in early life predisposes people to schizophrenia in later life
Early cannabis use (other drugs?)
Advancing parental age (germ cell mutations increase risk of schizophrenia development in the child.)
Is the risk of schizophrenia genetic?
Yes, increased risk in people with a family history
Amplification of risks in twin studies confirms this genetic contribution
Neuregulin and Dysbindin play a role in development and so are susceptibility genes as they influence neurodevelopment and synaptic function.
What are positive and negative symptoms in schizophrenia?
Acute positive, chronic negative
What is an example of positive symptoms?
Characteristic symptoms: thought insertion, 3rd person auditory hallucinations
Symptoms persistent for > 1 month
Exclusion of organic disease or a mood disorder such as bipolar already established
What is an example of negative symptoms?
Characteristic symptoms: flattened mood, indifference and loss of drive, social isolation, poor self-care, poverty of speech
What are other symptoms of schizophrenia not designated to positive and negative?
Cognitive impairment; affecting attention, working and semantic memory.
What is working memory?
Temporary storage and manipulation of information, needed for learning, reasoning and language comprehension
What is semantic memory?
Long term memory that processes ideas and concepts, inclusive of common knowledge such as colours, sounds of letters etc
What are sub syndromes in schizophrenia?
Paranoid schizophrenia - auditory delusions and hallucinations
Disorganised schizophrenia - thought disorder, odd behaviour, inappropriate mood
Catatonic schizophrenia - rare form due to the treatment of condition (taking anti-psychotics), symptoms include not being able to move or speak, person stares, holds body in a rigid position, unaware of surroundings
How is schizophrenia diagnosed?
Patients must have one or more of the following: 1. delusions 2. hallucinations Two of the following 1. delusions 2. hallucinations 3. disorganised speech 4. catatonic behaviour 5. negative symptoms i.e. flattened mood, inability to speak, general lack of drive
What is the dopamine theory behind the cause of schizophrenia?
Excess dopamine
Excess dopamine receptors
What is the evidence for the dopamine theory of schizophrenia?
Antipsychotic drugs = D2 receptors antagonists
Dopamine agonists such as amphetamines, levodopa = paranoid psychosis
CSF and brain studies from patients = abnormal levels of dopamine, its metabolites, enzymes or receptors.
Is dopamine excess the sole contributor to schizophrenia?
No, there is evidence that dopamine changes glutamate transmission downstream, signalling via the NMDA receptor is implicated.
NMDA antagonists ketamine and phenycylidine (PCP) prodce schizophrenia-like syndromes.
Other theories;
Abnormalities in cerebral blood flow and metabolism (impairment of neuronal circuits)
Specific impairment in frontal cortex, hippocampus, thalamus and cerebellum
In schizophrenic patients there are structural brain changes. What are these?
Enlargement of the lateral ventricles, slight decrease in the size of the brain, altered neuronal and synaptic organisation, affected white matter and no gliosis (no glial cell damage).
Neurodevelopmental (not neurodegenerative).
What kind of management strategy is employed for schizophrenia?
Depending on the stage of the illness;
Intervention includes physical, psychological and social.
Initial assessment requires compulsory admission, drug free if possible. Medication such as benzodiazepines may be needed to calm an acutely psychotic patient.
Aside from the management strategy, how are symptoms and treatment managed?
Antipsychotic medication effective against positive symptoms with gradual onset of therapeutic effect (2-3 weeks).
Investigate the context of positive symptoms i.e. drug misuse that may contravene treatment i.e. cannabis.
Family support is key, early intervention, CBT.
Similar treatment for chronic schizophrenia with regular monitoring.
What is the mechanism of action for pharmacological treatment?
Inhibit D2 receptors
Reverse excess dopamine activity in mesolimbic system (site for psychosis symptoms)
When treating a single schizophrenic episode how should treatment be carried out?
Maintained for 12-24 months after the episode
If improvement is noted then tail off medication because tardive dyskinesia is just one of many side effects
What is Tardive Dyskinesia?
Tardive dyskinesia (TD) is a medical term that describes the involuntary sudden, jerky or slow twisting movements of the face and/or body. Parkinsonian like side effect
What are the two main pros to using antipsychotics?
Effective against positive symptoms in around 70% of patients in the first 6 weeks
Useful in the prevention of psychosis relapse in delirium or severe depression
What determines the choice of antipsychotic?
Informed by the presentation of the patient
Patient’s choice
Side effect profile
Patient’s treatment history
What is recommended as treatment in the first instance?
6 weeks trial at adequate dosage to assess treatment response
What is it important to avoid in treatment?
Co-administration with anticholinergic agents, combinations of antipsychotics
Why might other treatment be needed alongside antipsychotics?
They have minor effects on negative and cognitive symptoms but are used mainly to exclude positive symptoms.
What is a key benefit to atypical antipsychotics?
Do not produce extrapyramidal side-effects at clinical doses (tardive dyskinesia)
What are the atypical antipsychotics? How do they work
Risperidone Olanzapine Amisulpride Quetiapine All D2 antagonists Aripiprazole (partial agonist)
Which novel formulation of risperidone is available?
Depot injection
Which useful side effect is found in olanzapine?
Sedative effects useful
What syndrome can be caused in olazapine use?
Metabolic syndrome; diabetes, obesity, high BP
What is a benefit of using amisulpride?
Some efficacy against negative symptoms
Which other mental health disorder can quetiapine be useful in?
Bipolar disorder (very sedating)
What is different about aripipazole compared to the other atypical antipsychotics?
It is a partial agonist, stabilises dopamine and antagonises when dopamine levels are too high
Mimics dopamine when levels are low
Acts depending on environment
What are some of the side effects in using atypical antipsychotics?
Weight gain
Hyperglycaemia and type 2 diabetes
Metabolic syndrome
What can make patients more susceptible to weight gain when they are taking atypical antipsychotics?
Genetic polymorphism 5-HT2C receptor
What kind of monitoring is needed when patients take an antipsychotic?
Monitoring of metabolic syndrome development i.e. dyslipidaemia and hypertension
What is used in patients that are resistant to atypical antipsychotics?
Clozapine
When is clozapine given?
Once the 6 weeks trials of two atypicals has been unsuccessful
What are the benefits to using clozapine?
Reduces the suicide risk in patients
Mechanism of greater efficacy but mechanism unknown
What are the drawbacks to clozapine?
Weekly blood tests are mandatory
What are the side effects of clozapine?
Also weight gain, metabolic syndrome but also hypersalivation, sedation and seizures at high doses
Which drugs are typical antipsychotics?
Chlorpromazine and haloperidol
What side effects do chlorpromazine and haloperidol have?
Extrapyramidal - motor abnormalities related to receptor blockade at basal ganglia
What is acute dystonia?
Painful contraction of muscles in the neck, jaw or eyes
Treated with anticholinergic agents
It is a side effect of typical antipsychotics and young men on high doses are particularly vulnerable
What is Parkinsonism and when can it occur?
Again, can occur in typical antipsychotic uses
Decreased facial movements, shuffling gait, stiffness and sometimes tremor
Common in early weeks of treatment
Treated by reducing dose or administering an anticholinergic agent
What is akathisia?
A feeling of restlessness and a need to walk around, very unpleasant
Treatment to lower dose or give propanolol
Again a side effect of typical antispychotics
What is tardive dyskinesia?
Avoided in atypical antipsychotics but a side effect of typical
Uncontrollable grimacing movement of face, tongue and upper body
Can be irreversible
What is neuroleptic malignant syndrome?
1 in 500, less common
Fatal in 10% of cases
Pyrexia, stiffness, autonomic instability (tachy and BP fluctuates)
Raised serum creatine kinase, metabolic acidosis
Stop the drug and monitor if patient develops fever without clear cause after the episode
What can happen to the QTRS of heart on ECG?
Prolongation of the QT interval on ECG
Predisposes to serious arrhythmia and probably related to the inhibition of K+ cardiac channels
What other drugs can be used in schizophrenia to treat symptoms?
Benzodiazepines: short term
Anti-depressants: administered as recommended by NICE
Electroconvulsive therapy can only be used in catatonic schizophrenia
Which non-pharmacological treatment can be used to help patients?
Family therapy
Focus: educate the family about the illness and changing their behaviour
Effectiveness is modest
Challenges are that it is difficult to implement widely due to financial constraints
How is CBT effective?
Effective against auditory hallucinations and delusions
Adopted as an integral part of management
Use of ear plugs and personal stereos also help re auditory hallucinations
