PBL Topic 3 Case 8 Flashcards
Outline the epidemiology of schizophrenia
- Affects 1% of population
- More common in makes
- Onset is usually between 16 and 25
Identify 3 genes implicated in the pathogenesis of schizophrenia
- Neuregulin (synaptic development and plasticity)
- Dysbindin (NMDA tethering)
- DISC-1 (Receptor trafficking)
Outline 2 environmental factors implicated in the pathogenesis of schizophrenia
- Maternal virus infections during pregnancy
- Cannabis consumption in adolescence and early adulthood
- Childhood sexual abuse
- Urban living
Which dopaminergic pathway is implicated in positive symptoms?
- Nigrostriatal pathway
- From substantia nigra pars compacta
- To association striatum
- Excess dopamine acting on D2 receptors
Which dopaminergic pathway is implicated in negative symptoms?
- Mesocortical pathway
- From ventral tegmental area of midbrain
- To prefrontal cortex
- Lack of dopamine acting on D1 receptors
Outline the role of glutamate in the pathogenesis of schizophrenia
- NMDA hypofunction reduces activity in mesocortical pathway and increased activity in mesolimbic pathway
- Reduce dopamine acting on inhibitory D1 receptors and increase dopamine acting on excitatory D2 receptors
What is the cause of neurodegeneration in schizophrenia?
- Glutamate induced excitotoxicity
Outline 5 positive symptoms of schizophrenia
- Paranoid delusions
- Hallucinations
- Thought disorder
- Disorganised behaviour
- Catatonia (immobility, purposeless motor activity)
Outline 4 negative symptoms of schizophrenia
- Withdrawal from social contact
- Flattening of emotional responses
- Anhedonia
- Reluctance to perform everyday tasks
What percentage of schizophrenia cases lead to suicidal attempts and successful suicide attempts respectively?
- 50%
- 10%
What is selective attention and how is it impaired in schizophrenia?
- Ability to focus on important information
- Schizophrenic patients fail to discriminate between significant and irrelevant stimuli
Outline 4 differential diagnoses of schizophrenia
- Organic mental disorders e.g. partial complex epilepsy
- Affective disorders e.g. mania
- Drug psychosis e.g. amphetamine psychosis
- Personality disorders e.g. schizotypal
Identify two first general antipsychotic drugs
- Chlorpromazine
- Haloperidol
Identify two atypical antipsychotic drugs
- Risperidone
- Clozapine
Explain how antipsychotics act on dopamine receptors and which type of symptom they reduce
- Antagonism of D2 receptors in nigrostriatal pathway, resulting in increased firing in nigrostriatal pathway
- Reduces positive symptoms
What side effects occur as a result of D2 antagonism and why do they occur?
- Systemic antipsychotics do not discriminate between D2 receptors in distinct brain regions
- Unwanted motor affects due to block of D2 receptors in nigrostriatal pathway (dorsal striatum)
- Enhanced prolactin secretion due to block of D2 receptors in tuberohypophyseal pathway
- Reduced pleasure due to block of D2 receptors in mesolimbic pathway
Why are 5-HT2a receptor antagonists important in the control of extrapyramidal side effects of antipsychotics?
- 5-HT2a receptors cause inhibition of dopaminergic nigrostriatal neurons
- Antagonism of these receptors enhances dopamine release into striatum
- So blocks unwanted motor affects of D2 blockage
Why are muscarinic acetylcholine receptor antagonists important in the control of extrapyramidal side effects of antipsychotics?
- D2 blockage in striatum results in enhanced ACh release on muscarinic receptors
- Which further inhibits D2 receptors??
What is acute dystonia?
- Reversible extrapyramidal motor side-effect of antipsychotics
- Beginning within the first few weeks
- Characterised by fixed upward gaze, torticollis (involuntary spasm of neck muscles) and restlessness
What is tardive dyskinesia?
- Irreversible extrapyramidal motor side-effect of antipsychotics
- Beginning after months or years in a fifth of patients
- Characterised by athetosis (writhing movements of the face, neck and limbs), chorea
- Resembles effects of levodopa in Parkinson’s
What are the effects of enhanced prolactin concentration?
- Dopamine acts on D2 receptors in tuberohypophyseal pathway to inhibit prolactin secretion
- Blockage of receptors results in breast swelling, and lactation
What are the effects of blockage of histamine receptors by antipsychotics?
- Drowsiness
- Sedation
What are the effects of blockage of muscarinic receptors by antipsychotics?
- Blurred vision
- Increased intraocular pressure
- Dry mouth
- Dry eyes
What are the effects of blockage of alpha adrenoreceptors receptors by antipsychotics?
- Orthostatic hypotension
What are the effects of blockage of 5-HT receptors by antipsychotics?
- Weight gain
- Increased risk of diabetes and cardiovascular disease
What is antipsychotic malignant syndrome?
- Muscle rigidity and rapid rise in body temperature
What does psychological treatment of schizophrenia involve?
- Reassurance and support
- CBT to reduce intensity of delusions
- Psychotherapy is contraindicated
What does social treatment of schizophrenia involve?
- Attention paid to patient’s environment and social functioning
- Family education on optimal amount of emotional and social stimulation
- Sheltered employment
- Assertive outreach mental health teams for poor adherence to medication
Outline the prognosis for schizophrenia
- 25% have good outcome
- 33% develop chronic schizophrenia
- Most will not work or live independently
- 1 in 10 take their own lives
What is the role of the early intervention service?
- Address needs of patients during period of untreated psychosis (between first episode and receiving of effective treatment)
- To improve symptom severity, admission rates, relapse rates and prognosis
What is the role of the care-coordinator in the EIS and who typically carries out this role?
- Ensure everyone is working together to identify patients needs
- Community psychiatric nurse/occupational therapist/social worker
What is the role of Approved Mental Health Practitioners in the EIS?
- Make decisions about whether a person should be admitted to hospital for assessment or treatment
What is the role of the psychiatrists in the EIS?
- Specialise in diagnosis and treatment
What is the active principle of cannabis?
- Cannabinoids
- The most abundent of which is delta 9 tetrahydrocannabinol (THC)
What is cannabidiol?
- Precursor of THC
What is cannabinol?
- Breakdown product from THC
What is meant by a psychotomimetic effect?
- Produces hallucinations and delusions
How do the effects of cannabis differ to ethanol?
- Cannabis does not produce reckless and aggressive behaviour
Outline subjective effects of cannabis
- Relaxation
- Wellbeing
- Sharpened sensory awareness
- Time passes extremely slowly
Outline six adverse central effects of cannabis
- Impairment of short-term memory and simple learning tasks
- Impairment of motor co-ordination
- Catalepsy
- Hypothermia
- Analgesia
- Increased appetite
Outline five peripheral adverse effects of cannabis
- Tachycardia
- Vasodilation (scleral and conjunctival vessels producing bloodshot eyes)
- Reduction in intraocular pressure
- Bronchodilation
What is the time frame of the effects of cannabis?
- Takes 1 hour to develop
- Lasts between 2 and 3 hours
Outline the distribution of CB1 receptors and how these relate to their central effects
- Hippocampus (impaired memory)
- Cerebellum (impaired co-ordination)
- Hypothalamus (increased appetite and hypothermia)
- Substantia nigra (impaired motor control)
Where are CB2 receptors located?
- Lymphoid tissue including
- Spleen, tonsils, thymus,
- Lymphocytes, monocytes, mast cells, microglia
Describe CB1 receptors
- G protein coupled receptors located presynaptically
- Activation of inward-rectifying potassium channels causing hyperpolarisation
- Also influences gene expression by acting on mitogen activating protein kinase
What are endocannabinoids?
- Endogenous ligands for CB receptors
- Made on demand (eicosanoid)
- Their role is retrograde mediations passing information from postsynaptic neurons
Identify two endocannabinoids
- Anandamide
- 2-AG
What is the role of fatty acid amide hydrolase (FAAH)?
- Inactivated anandamide
- Converting it to arachidonic acid and ethanolamine
Identify a stimuli that causes release of endocannabinoids
- Increased intracellular Ca2+
What is meant by depolarisation induced suppression of inhibition (DSI)?
- Depolarisation of hippocampal pyramidal cells
- Causing suppression of GABA mediated inhibition input to these cells
- Implying a retrograde flow of information by activation of CB receptors
- Inhibited by CB1 antagonists e.g. rimonabant
How does NMDA hypofunction cause positive symptoms?
- NMDA hypofunction on GABAergic neurons
- Resulting in disinhibition of glutamatergic neurons in the PcSN
- Increased dopamine release from PcSN acting on D2 receptors in associative striatum
How does NMDA hypofunction cause negative symptoms?
- NMDA hypofunction on GABAergic neurons
- Resulting in disinhibition of glutamatergic neurons on GABA neurons
- Inhibiting ventral tegmental area
- Reduce D1 in mesocortical pathway
Outline the diagnostic criteria for schizophrenia
- At least 1 symptom for at least 1 month:
- Hallucination
- Delusions
- Withdrawal
How long should antipsychotics be taken to be maximally effective?
- 2-4 weeks
In patients with a first psychotic episode, how long should antipsychotic treatment be continued for in order to prevent relapse
- 1-2 years
What is the dose of risperidone?
- Orally up to 4 mg
Explain the relationship between FAAH and pain threshold?
- Endocannabinoids have analgesic and anxiolytic properties
- Capable of reducing anxiety and increased pain threshold
- FAAH inhibition increases endocannabinoids concentration
What is rimonabant and what are its clinical effects?
- CB1 receptor antagonist
- Increased weight loss
- Reduced tobacco dependence and drug addiction
What percentage block of D2 receptors is required for therapeutic effects of antipsychotics?
-65% to 80%
What is meant by sectioning?
- Person is kept in hospital under Mental Health Act 1983
Identify three criteria for sectioning
- Patients needs assessment and treatment
- Patients health would otherwise deteriorate
- Their own safety or safety of others is impaired
Outline Section 2 of the MHA
- Patient can be detained if they have a mental disorder that poses risks to their own safety or safety of others
- And they need to be detained for a short time for assessment (up to 28 days)
Outline Section 3 of the MHA
- Patient can be detained if they have a mental disorder that poses risks to their own safety or safety of others
- Treatment can only be given in hospital
- Can be detained for up to 6 months
Who is able to extent or renew sectioning under Section 3?
- Responsible clinician
For how many months can Section 3 be extended:
[A] The first time
[B] The second time
[C] The third time
- [A] 6 months
- [B] 6 months
- [C] 12 months
Who is responsible for discharging the patient?
- Responsible clinician
What is the role of the Approved Mental Health Professional?
- Co-ordination of assessment and admission to hospital
Aside from the AMHP, identify two other roles involved in assessment and admission
- Registered GP, ideally one who knows the patient
- Section 12 approved doctor e.g. psychiatrist
What right’s does the nearest relative have?
- They can tell the AMHP their concerns which may lead to sectioning
- They should be consulted if the AMHP wants to section the patient
- They have the right to object to sectioning
What is the role of the independent mental health advocate?
- Help patient express patients views if they refuse sectioning
What is escorted leave and who grants permission?
- Patient can leave ward for good reason
- Permission clinician
- Hospital is not under legal obligation to do this
Can patients be given treatment against their will?
- Yes
What happens when a patient refuses sectioning?
- AMHP can use reasonable force or can involve the police
What is meant by recovery?
- A way of living a satisfying, hopeful and contributing life even with the limitations caused by illness
What is a Wood Shedding Model or recovery?
- Following an initial improvement, the individual’s condition may ‘plateau’ for long periods
- And then suddenly improve in a discontinuous manner.
Identify internal and external conditions of recovery
- Internal: Hope
- External: Human rights
