Schizophrenia Flashcards
When is the common onset of Schizophrenia?
- Late adolescence
- Early adulthood
(acute onset over 2 - 3 weeks)
What is the median age of onset?
Median age of onset:
M: 23 years
F: 28 years
Is there a greater prevalence of Schizophrenia in one gender? Why could this be so?
- More prevalent in males than females
- Oestrogen has a role in regulating dopamine receptor sensitivity, hence increased prevalence in males.
What is the environmental aetiology (cause) of Schizophrenia?
- Males in urban areas are prone to schizophrenia
- More prevalent in countries further from equator (cold weather; affects mothers e.g. viral infection, affects foetus)
- Perinatal complications: severe malnutrition, exposure to stressful events, birth complications, altered brain development in early life
- Early cannabis use
- Advancing paternal age; germ cell (sperm) mutations increase risk of Schizophrenia in child.
What is the genetic aetiology of Schizophrenia?
- Family history
- Twin studies validates a genetic contribution; 50% chance other monozygotic twin has it if the other does
Susceptibility genes
- Neuregulin & Dysbindin
- Influence neurodevelopment and synaptic functioning
- Can lead to Schizophrenia
What are the positive symptoms of Schizophrenia? How do they present?
Acute presentation:
- Thought insertion
- 3rd person auditory hallucinations
- Thought disorder (e.g. cutting out mid-sentence, not knowing what’s happened after)
- Delusional perception
Duration criteria:
- Symptoms persist for > 1 month
What are the exclusion criterion for positive symptom presentation of Schizophrenia?
- Not secondary to mood disorder (exclude bipolar disorder e.g. ramblings)
- No organic disease
What are the negative symptoms of Schizophrenia? How do they present?
Chronic presentation: - Flattened mood - Indifference and loss of drive - Social isolation >>> (Similar to depression) - Poor self-care - Poverty of speech
Negative symptoms are relatively nonspecific; could be passed off as ‘teenage years’ etc.
What else presents for Schizophrenia apart from positive and negative symptoms?
Cognitive impairment:
- Affects attention, working and semantic memory (long-term memory not drawn from personal experience)
- Link to dementia in elderly schizophrenic patients?
Define: working memory.
Working memory (can affect academia):
- Temporary storage and manipulation of information
- Necessary for tasks such as language comprehension, learning and reasoning
Define: semantic memory.
- Long term memory that processes ideas and concepts
- Inclusive of common knowledge: colours, sounds of letters etc.
What sub syndromes of Schizophrenia are there?
- Paranoid schizophrenia
- Disorganised schizophrenia
- Catatonic schizophrenia
What is paranoid schizophrenia?
Auditory delusions and hallucinations
What is disorganised schizophrenia?
- Thought disorder
- Odd behaviour
- Inappropriate mood
What is catatonic schizophrenia?
- Due to treatment of the condition (schizophrenia)
- Rare form
- Debilitating condition
Symptoms:
- Unable to move or speak
- Person stares
- Holds body rigidly
- Unaware of surroundings
How is schizophrenia diagnosed?
One or more of (if clear cut:
- Delusions
- Hallucinations
Two of:
- Delusions
- Hallucinations
- Disorganised speech
- Catatonic behaviour
- Negative symptoms; flattened mood, inability to speak, general lack of drive
What is the dopamine theory of schizophrenia origin?
- Excess dopamine
- Excess dopamine receptors
(Parkinson’s = opposite; depletion of DA)
What is the evidence to support the dopamine theory of schizophrenia?
- Antipsychotic drugs = D2 receptor antagonists (too much DA)
- DA agonists such as amphetamines, levodopa cause paranoid psychosis
- CSF and brain studies of patients; abnormal levels of DA, its metabolites, enzymes or receptors
What is the evidence that DA is not the sole contributor to schizophrenia?
- DA changes Glu transmission downstream
- Signalling via NMDA is implicated
- NMDA receptor antagonists e.g. ketamine, phencyclidine (PCP) produce schizophrenia-like syndrome
- Thus depletion of Glu = schizophrenia symptoms
What other theories aside from the DA/Glu theory are there for the cause of schizophrenia?
Functional imaging studies:
- Abnormalities in cerebral blood flow and metabolism - impairment of neuronal circuits
- Specific impairment in frontal cortex, hippocampus, thalamus and cerebellum (hence delusions)
Structural brain changes:
- Enlargement of lateral ventricles
- Slight decrease in size of brain
- Histology; altered neuronal and synaptic organisation, affected white matter, no gliosis (absence of neurodegenerative process) THUS
»> schizophrenia = neurodevelopmental, not neurodegenerative.
What is the management strategy for schizophrenia?
Based on stage of illness: Intervention: - Physical (pharmacological therapy) - Psychological - Social (family, care home)
Initial assessment:
- Compulsory admission required (upon initial psychiatric event)
- Drug free if possible; might have to give benzodiazepine to calm them down
How is schizophrenia managed? How long do antipsychotics take to take effect? What do they combat?
- Antipsychotics effective against most positive symptoms
- Gradual onset of therapeutic effect (2-3 weeks(
- Investigate context; substance misuse (cannabis) may contravene treatment
- Family support is key
»> Early intervention; CBT, antipsychotics
What is the mechanism of action for antipsychotics?
- Inhibit D2 receptors
- Reverse excess DA activity in mesolimbic system; site for psychosis symptoms
How long is antipsychotic treatment continued for after initial psychosis? How does treatment change over time?
- 12-24 months; after ONE single episode.
- Tail off medication if improvement noted; tardive dyskinesia and other S/Es.
What is tardive dyskinesia?
Involuntary movement of the tongue, lips, face, tongue and extremities.
Do antipsychotics have effect against positive symptoms?
- Yes; within 6 weeks in 70% of patients
- Useful in prevention of psychosis relapse in delirium (mental confusion) and severe depression
How is antipsychotic drug therapy chosen?
- Informed by patient presentation
- Patient’s choice (in conjunction w/HCP, carer)
- S/E profile
- Treatment history
> > > 6 week trial at adequate dosage to assess treatment response (switch to another after 2 weeks if not even minimal improvement)
What should be avoided when receiving antipsychotic drug therapy?
- Co-administration w/anticholinergic/antimuscarinic agents
- Combinations of antipsychotics; exacerbate antimuscarinic S/Es
Which symptoms do antipsychotics treat the best?
- Positive symptoms
- Antipsychotics have minor effects on negative and cognitive symptoms
Why are atypical (second generation) antipsychotics generally preferred to typical (first generation) antipsychotics?
- Atypicals do not produce extrapyramidal S/Es (Parkinson’s-like tremors) at clinical doses
- Similar profile to typicals otherwise
What is the hierarchy of atypical antipsychotics, and their advs/disadvs?
1) Risperidone; availible as depot too
2) Olanzapine; sedative effects useful, BUT may cause metabolic syndrome (HBP, diabetes, obesity)
3) Amisulpride; some efficacy against negative symptoms
4) Quetiapine; quite sedating, beneficial in treating bipolar depression
5) Aripiprazole; acts as DA partial agonist, ‘stabilises’ DA, antagonises DA when levels are high, mimics DA when levels are low.
What are the S/Es w/atypical antipsychotics?
Weight gain:
- Mean weight gain of 5kg over 6 months
- Genetic polymorphism of 5-HT2C receptor?
Hyperglycaemia and Type 2 DM:
- Increased incidence of Type 2 DM
- Occurs from drug-induced hyperglycaemia and insulin resistance
Metabolic syndrome:
- Screening required prior to and during treatment.
What is Metabolic syndrome?
Dyslipidemia and hypertension make up metabolic syndrome, in addition to Type 2 DM and hyperglycaemia
How effective is the atypical, clozapine?
- Effective in 30% of patients resistant to other drugs
- Used when failure to respond to two 6 week trials
- Reduces suicide risk in schizophrenia
- Mechanism of greater efficacy not known
Why is clozapine reserved as a 3rd line agent, given its efficacy? What precautions must be taken as a result?
Agranulocytosis: bone marrow suppression (suppressing WBCs inc. neutrophils = prone to infection)
- Thus reserved for treatment-resistant patients
»> Weekly blood tests mandatory
Other S/Es:
- Weight gain
- Metabolic syndrome
- Hypersalivation
- Sedation
- Seizures (at high doses)
What are some typical (first generation) antipsychotics? What advantages do they have?
- Chlorpromazine
- Haloperidol
»> Cheap and efficacious BUT S/E profile
What is the characteristic side effect of typical antipsychotics?
Extrapyramidal symptoms; motor abnormalities related to receptor blockade in basal ganglia (normally coordinates movement, filters out unnecessary movements etc..
List the side effects associated w/typical antipsychotics.
- Acute dystonia
- Parkinsonism
- Akathisia
- Tardive dyskinesia
- Neuroleptic malignant syndrome
- Prolongation of the QT interval (ECG)
What is Acute dystonia? Treatment?
- Painful contractions of muscles in the neck, jaw or eyes (spasms set of by ACh)
- Young men given high doses of typical antipsychotics particularly vulnerable; onset within hours or days
»> Treatment: IM or IV anticholinergic agents
What does Parkinsonism entail? Treatment?
- Decreased facial movements, shuffling gait, stiffness, sometimes tremor
- Common in early weeks of treatment
»> Treatment: reduce dose (too little DA = symptoms), or administer anticholinergic agent
What does Akathisia entail? Treatment?
- Feeling of restlessness and need to walk around
- Very unpleasant, occurs in first few months
»> Treatment: lower dose, or propanolol
What does Tardive Dyskinesia (TD) entail? Treatment?
- Uncontrollable grimacing movements of face, tongue, upper body
- Distressing and disabling
- Occurs in 5% of patients taking long-term typicals
- No way of predicting
- Can be irreversible
»> Treatment: no reliable treatment availible; titrate down dose after patient presents w/TK
What is Neuroleptic malignant syndrome? Treatment?
- 1 in 500 (Fatal in 10%)
- Pyrexia, stiffness, autonomic instability (tachycardia, fluctuating BP) and seizures; leading to coma.
- Characteristics: raised serum creatine kinase (byproduct of muscle damage), metabolic acidosis (low pH), leucocytosis (elevated leukocytes)
»> Treatment: just stop the drug, monitor if patient develops fever w/o a clear cause - After an episode; restart treatment gradually, switch to atypical, careful monitoring
What does prolongation of the QT interval mean?
- Predisposes to serious arrhythmia
- Inhibition of specific cardiac K+ channels
What other drugs are involved in the pharmacological management of schizophrenia?
Benzodiazepines:
- Short term treatment (target negative symptoms)
Antidepressants:
- Treatment administered as recommended by NICE
Electroconvulsive treatment
- Not effective unless in catatonic schizophrenia (treatment-induced)
What does psychological treatment entail for schizophrenia?
Family therapy:
- Focus; educate family, changing their behaviour
- Effectiveness; modest
- Challenges; difficult to implement widely due to financial constraints
CBT:
- Some efficacy against auditory hallucinations and delusions
- Adopted as integral component of schizophrenia management
- Hallucinations can also benefit from simple practical manoeuvres; use of ear plugs or personal stereos “drown out noise”
»> But can be counter-productive; voices saying “Why are you trying to get rid of me?” etc.
