Schizophrenia and its causes symposium Flashcards
List the features of psychosis
Positive symptoms - Delusions, hallucinations, disorganized speech, catatonia
Negative symptoms - Affective flattening, Alogia, Avolition, Anhedonia
Cognitive symptoms - attention, memory, executive functions
Mood symptoms - dysphoria, suicidality, helplessness
Affects social, work, family and self care
Describe the genetics of schizophrenia
Relatives of affected subject with psychosis have an increased risk of psychosis themself
Effects shown in monozygotic twins 50% chance
In adoption there is an increase risk if biological parents have schizophrenia
Major histocompatibility complex on chromosome 6 gene encoding micro RNA mi147 associated with neuronal development. TCF4 CSMD1 Region of chromosome 10 NGRN In joint with bipolar disorder - ZNF804A, CACNA1C and ANK3 Copy note variants identified Likely multiple genes of small effect
List some environmental/biological stresses causing schizophrenia
Obstetric complications - Premature birth, low birth weight, perinatal hypoxia
Intrauterine infection 1st/2nd trimester
Antepartum bleeding
Immune activation
List some environmental/psychological stresses causing schizophrenia
Life events Migration Social isolation urban living Upbringing - high emotional expression in families - critical comments, hostility, overinvolvement Early experience of trauma
List some macro neurological abnormalities reported in schizophrenia
Enlargement of ventricles Widening of cortical sulci Cortical grey matter loss Loss of asymmetry Decrease limbic structure and thalamic volume Progressive deficits in some and not all
List some micro abnormalities reported in schizophrenia
Cortical glial loss Increased neuron density Aberrant neuron migration Synaptic loss Decreased dendritic complexity
Neuropsychology abnormalities
Deficits in : Arousal Working memory Executive function Eye movements Social cognition Theory of mind Loss of functional asymmetry Receptive language function Subtle motor function, speech and IQ
What happens to striatal dopamine synthesis and storage in schizophrenia?
Increases
What is associated with increased dopamine secretion in the striatum?
Reduced glutamate function in the frontal lobes
What symptoms is reduced frontal glutamate associated with?
Negative symptoms
What symptoms is increased striatal dopamine associated with?
Positive symptoms
What does hypoactivity in the PFC lead to?
Increased dopamine release in nucleus accumbens
Which symptoms in particular is glutamate associated with?
Cognitive
List some drugs associated with psychosis
L-Dopa Amphetamine LSD Cannabis Cocaine Ketamine MDMA PCP other novel psychoactives
List affective psychosis disorders
Bipolar disorder
Depressive psychosis
Schizoaffective disorder
List organic psychosis
Epilepsy (temporal lobe)
Infections: encephalitis, subacute sclerosing panencephalitis, neurosyphillis, HIV
Cerebral trauma
Cerebrovascular disease
Demyelination: MS, Schilder’s disease, metachromatic dystrophy
Neurodevelopmental disorders: velocardiofacial syndrome
Endocrine: thyroid disorders (hyper and hypo), Cushing’s syndrome,
Metabolic: hepatic failure, uraemia
Immunological: SLE, Autoantibodies to brain receptors NMDA
Drugs
Toxins eg. lead
Dementias
What is the differential diagnosis of psychosis?
Affective psychosis
Organic psychosis
Personality disorder
What do antipsychotic drugs treat?
Dopamine dysregualtion
What does CBT treat?
Cognitive salience errors
Which classes of drugs are used to treat psychosis?
Typical and Atypical antipsychotics
Compare the efficacy of typical vs atypical antipsychotics
Appears equal in first psychotic episode however atypical antipsychotics may be more useful in chronic illness
Which drug has greatest efficacy in resistant cases?
Clozapine
How long does it take till clinical evidence of efficacy can be seen in patients?
2 Weeks
How are side effects predicted?
By receptor affinity of the drug
List the adverse effects of drugs which bind to D2 Dopamine receptors
Parkinsonism, tardive dyskinesia, raised prolactin
List the adverse effects of drugs which bind to 5FT2 serotonin receptors
Sedation, metabolic weight gain, glucose intolerance, increased triglycerides, raised prolactin, hypotension, arrhythmia, neutropenia
List the adverse effects of drugs which bind to H1 histamine receptors
Sedation
Weight gain
List the adverse effects of drugs which bind to M1 cholinergic receptors
Antagonism - constipation, urinary retention, blurred vision
Agonism (clozapine only) - saliva overproduction
List the adverse effect of drugs which bind to alpha 1 norepinephrine receptors
Postural hypotension
List some typical antipsychotics
HALOPERIDOL
CHLORPROMAZINE
List some typical antipsychotics
AMISULPRIDE ARIPIPRAZOLE CLOZAPINE RISPERIDONE OLANZAPINE QUETIAPINE LURASIDONE
List some long acting injections
DEPIXOL PALOPERIDONE (RISPERIDONE
CLOPIXOL (OLANZAPINE)
PIPORTIL ARIPIPRAZOLE
How do the typical (old) antipsychotics work?
Potently block dopamine D2 receptors
List the side effects of typical antipsychotics
Sedation
Extrapyramidal symptoms Parkinsonian symptoms
Dystonia
Akithisia
Tardive dyskinesia
Cardiac: Hypotension, Arrhythmias
Temperature dysregulation
Neuroleptic malignant syndrome
Anticholinergic side effects (affect many different organs)
Weight gain (less than atypicicals)
Raised prolactin (galactorrhoea, ↓sexual fn, osteoporosis)
Less frequently jaundice, lens opacities, skin discolouration, blood dyscrasias
Describe the action of atypical (new) antipsychotics
Primary action not at D2 receptors, often more potent at 5HT2 receptors
List the side effects of atypical antipsychotics
Sedation (olanzapine, clozapine, quetiapine) (least for aripiprazole)
Metabolic weight gain, glucose intolerance, ↑triglycerides (olanzapine / clozapine more than others; least for aripiprazole)
Raised prolactin :galactorrhoea, ↓sexual fn, osteoporosis (risperidone, amisulpride)
Cardiac: Hypotension (quetiapine) Arrhythmias (less than typicals)
Neutropaenia with clozapine in 1% hence requires regular blood monitoring
Describe the NICE standards for antipsychotic use
Joint choice of drug with patient / carer / Dr
Use Clozapine if no response to 2 others (including 1 atypical)
Log acting (depot) injections useful in those who prefer them or to help covert non adherence
Develop advance directives
Avoid high dose or prescription of two antipsychotics together
Describe clozapine
Oral medication taken daily.
Clear benefit in treatment resistant schizophrenia.
Little Parkinsonian effects or tardive dyskinesia.
Sedation, weight gain, dribbling common.
What monitoring is required in clozapine use?
Licensed with regular neutrophil monitoring.
Neutropenia in approximately 1% of cases but progression slow so ceasing medication significantly reduces risk.
Slow titration to optimal dose with monitoring of pulse, BP and neutrophil count necessary.
Describe the use of electroconvulsive treatment
Not a primary treatment of psychosis
Very effective in psychosis associated with depression or with catatonia
What is metabolic syndrome and how does it relate to schizophrenia?
Exacerbated by atypical antipsychotic drugs
Appears more prevalent in schizophrenia pre treatment
than the general population
Associated with higher rates of coronary heart disease,
cerebrovascular pathology and earlier death
Hence routine screening, appropriate treatment
and giving routine advice about diet & exercise in
psychiatric practice
Why not just medication?
Treatment resistant symptoms
Partially resistant symptoms
Where side effects limit doses of medication
Service user choice
Comorbidity….anxiety, depression, PTSD
psychologically informed case management.- relapse prevention
What is the ethos of early interventional service?
Hopeful
Collaborative
Empowering
Social recovery prioritised….achieving work, relationships
Describe CBT informed case management
Timeline of events leading to psychosis
Relapse signature
Early warning signs
Crisis plan
Problem solving
Psychoeducation about illness and possible treatment options
Self management , advance directives
List some NICE recommended psychological treatments in schizophrenia
Offer Cognitive behavioural therapy for psychosis CBTp
Offer Family interventions for families
Consider Art therapy
Assess for PTSD and follow PTSD guidelines
List some treatments for the comorbidities of schizophrenia
Depression... behavioural activation Bipolar……mood management Trauma…..trauma related work. EMDR Anger management Anxiety….relaxation, graded exposure work
Medication concordance
Describe CBT for psychosis
12-20 sessions
Treatment resistant symptoms
Alternative to medication for distressing symptoms
Aim is to relieve distress and increase function rather than “treat” delusions or “get rid” of hallucinations.
What is the CBT model
Thoughts
Feelings
Behaviour
What does CBT work on?
Appraisal of a situation Jumping to conclusions Working on delusional belief Changing appraisal of experiences Work on reasonable biasness Work on self esteem Work on appraisal of meaning of having psychosis
Describe family interventions
Psychoeducation for families
Support for families, friends and family groups.
Specific coping strategies
Specific psychosis based family intervention
What is behavioural family therapy?
Highly structured therapy
Based on work of Vaughn and Leff 1976 on expressed emotion and risk of relapse.
12-16 sessions
2 therapists
Ideally patients who have relapsed and are in close contact with family
What does behavioural family therapy involve?
Sharing Information about mental health problems and treatment
Problem solving
Crisis management
Managing medication compliance
Demonstrating and working on good communication between family members
Encouraging family members to refocus on own lives rather than the individual with the psychosis.
List some family therapy techniques
Sculpting
Reframing
Circular questions
Reflecting teams
What is art therapy useful for?
Negative symptoms
Concentration
Isolation
Self confidence
Creative medium to help explore and articulate feelings rather than speaking about them. safe space and relationship with therapists.
