Schizophrenia and its causes symposium

Question 1

List the features of psychosis

Answer 1

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

Question 2

Describe the genetics of schizophrenia

Answer 2

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

Question 3

List some environmental/biological stresses causing schizophrenia

Answer 3

Obstetric complications - Premature birth, low birth weight, perinatal hypoxia
Intrauterine infection 1st/2nd trimester
Antepartum bleeding
Immune activation

Question 4

List some environmental/psychological stresses causing schizophrenia

Answer 4

Life events
Migration
Social isolation
urban living
Upbringing - high emotional expression in families - critical comments, hostility, overinvolvement
Early experience of trauma

Question 5

List some macro neurological abnormalities reported in schizophrenia

Answer 5

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

Question 6

List some micro abnormalities reported in schizophrenia

Answer 6

Cortical glial loss
Increased neuron density 
Aberrant neuron migration
Synaptic loss
Decreased dendritic complexity

Question 7

Neuropsychology abnormalities

Answer 7

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

Question 8

What happens to striatal dopamine synthesis and storage in schizophrenia?

Answer 8

Increases

Question 9

What is associated with increased dopamine secretion in the striatum?

Answer 9

Reduced glutamate function in the frontal lobes

Question 10

What symptoms is reduced frontal glutamate associated with?

Answer 10

Negative symptoms

Question 11

What symptoms is increased striatal dopamine associated with?

Answer 11

Positive symptoms

Question 12

What does hypoactivity in the PFC lead to?

Answer 12

Increased dopamine release in nucleus accumbens

Question 13

Which symptoms in particular is glutamate associated with?

Answer 13

Cognitive

Question 14

List some drugs associated with psychosis

Answer 14

L-Dopa				
Amphetamine			
LSD
Cannabis 
Cocaine
Ketamine
MDMA         
PCP  
other novel psychoactives

Question 15

List affective psychosis disorders

Answer 15

Bipolar disorder
Depressive psychosis
Schizoaffective disorder

Question 16

List organic psychosis

Answer 16

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

Question 17

What is the differential diagnosis of psychosis?

Answer 17

Affective psychosis
Organic psychosis
Personality disorder

Question 18

What do antipsychotic drugs treat?

Answer 18

Dopamine dysregualtion

Question 19

What does CBT treat?

Answer 19

Cognitive salience errors

Question 20

Which classes of drugs are used to treat psychosis?

Answer 20

Typical and Atypical antipsychotics

Question 21

Compare the efficacy of typical vs atypical antipsychotics

Answer 21

Appears equal in first psychotic episode however atypical antipsychotics may be more useful in chronic illness

Question 22

Which drug has greatest efficacy in resistant cases?

Answer 22

Clozapine

Question 23

How long does it take till clinical evidence of efficacy can be seen in patients?

Answer 23

2 Weeks

Question 24

How are side effects predicted?

Answer 24

By receptor affinity of the drug

Question 25

List the adverse effects of drugs which bind to D2 Dopamine receptors

Answer 25

Parkinsonism, tardive dyskinesia, raised prolactin

Question 26

List the adverse effects of drugs which bind to 5FT2 serotonin receptors

Answer 26

Sedation, metabolic weight gain, glucose intolerance, increased triglycerides, raised prolactin, hypotension, arrhythmia, neutropenia

Question 27

List the adverse effects of drugs which bind to H1 histamine receptors

Answer 27

Sedation | Weight gain

Question 28

List the adverse effects of drugs which bind to M1 cholinergic receptors

Answer 28

Antagonism - constipation, urinary retention, blurred vision Agonism (clozapine only) - saliva overproduction

Question 29

List the adverse effect of drugs which bind to alpha 1 norepinephrine receptors

Answer 29

Postural hypotension

Question 30

List some typical antipsychotics

Answer 30

HALOPERIDOL | CHLORPROMAZINE

Question 31

List some typical antipsychotics

Answer 31

``` AMISULPRIDE ARIPIPRAZOLE CLOZAPINE RISPERIDONE OLANZAPINE QUETIAPINE LURASIDONE ```

Question 32

List some long acting injections

Answer 32

DEPIXOL PALOPERIDONE (RISPERIDONE CLOPIXOL (OLANZAPINE) PIPORTIL ARIPIPRAZOLE

Question 33

How do the typical (old) antipsychotics work?

Answer 33

Potently block dopamine D2 receptors

Question 34

List the side effects of typical antipsychotics

Answer 34

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

Question 35

Describe the action of atypical (new) antipsychotics

Answer 35

Primary action not at D2 receptors, often more potent at 5HT2 receptors

Question 36

List the side effects of atypical antipsychotics

Answer 36

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

Question 37

Describe the NICE standards for antipsychotic use

Answer 37

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

Question 38

Describe clozapine

Answer 38

Oral medication taken daily. Clear benefit in treatment resistant schizophrenia. Little Parkinsonian effects or tardive dyskinesia. Sedation, weight gain, dribbling common.

Question 39

What monitoring is required in clozapine use?

Answer 39

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.

Question 40

Describe the use of electroconvulsive treatment

Answer 40

Not a primary treatment of psychosis | Very effective in psychosis associated with depression or with catatonia

Question 41

What is metabolic syndrome and how does it relate to schizophrenia?

Answer 41

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

Question 42

Why not just medication?

Answer 42

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

Question 43

What is the ethos of early interventional service?

Answer 43

Hopeful Collaborative Empowering Social recovery prioritised….achieving work, relationships

Question 44

Describe CBT informed case management

Answer 44

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

Question 45

List some NICE recommended psychological treatments in schizophrenia

Answer 45

Offer Cognitive behavioural therapy for psychosis CBTp Offer Family interventions for families Consider Art therapy Assess for PTSD and follow PTSD guidelines

Question 46

List some treatments for the comorbidities of schizophrenia

Answer 46

``` Depression... behavioural activation Bipolar……mood management Trauma…..trauma related work. EMDR Anger management Anxiety….relaxation, graded exposure work ``` Medication concordance

Question 47

Describe CBT for psychosis

Answer 47

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.

Question 48

What is the CBT model

Answer 48

Thoughts Feelings Behaviour

Question 49

What does CBT work on?

Answer 49

``` 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 ```

Question 50

Describe family interventions

Answer 50

Psychoeducation for families Support for families, friends and family groups. Specific coping strategies Specific psychosis based family intervention

Question 51

What is behavioural family therapy?

Answer 51

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

Question 52

What does behavioural family therapy involve?

Answer 52

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.

Question 53

List some family therapy techniques

Answer 53

Sculpting Reframing Circular questions Reflecting teams

Question 54

What is art therapy useful for?

Answer 54

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.