Schizophrenia and its causes symposium Flashcards by yeswanth AKULA

Symptoms of psychosis

Delusions
Hallucinations
Disorganised speech
Catatonia

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Cognitive effects of schizophrenia

Attention
Memory
Executive functions(eg abstraction)

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Negative symptoms of schizophrenia

Affective flatterning
Alogia
Avolition
Anhedonia

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Mood symptoms of schizophrenia

Dysphoria
Suicidality
Helplessness

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How are relatives of schizophrenic patients affected

Increased risk of psychosis

- Increase in rate of schizotypal relatives

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%risk - parent

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%risk - sibling

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%risk child

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%risk child of 2 affected parents

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Obstetric complications that increase risk

Premature birth
Low birth weight
Perinatal hypoxia

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Effect of migration on risk

Increases risk of psychosis

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Macro neurodevelopmental abnormalities reported in schizophrenia

Ventricular enlargement

widening cortical sulci

cortical grey matter loss

loss of asymmetry

↓limbic structure and thalamic volume

Progressive deficits in some, not all

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Micro neurodevelopmental abnormalities reported in schizophrenia

Cortical glial loss 
Increase in neurone density
Aberrant neurone migration 
Synaptic loss 
Decrease in dendritic complexity

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Neuropsychology abnormalities in schizophrenia

Deficits in     
Attention
Arousal (too much)
Working memory 
Executive function
Eye movement (saccadic, smooth pursuit) 
Social cognition (recognising facial emotions / social cues)
Theory of mind 
Loss of functional asymmetry
Receptive language function          
Subtle motor function, Speech, IQ

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Where is dopamine synthesis and storage increased in schizophrenia

Striatal dopamine synthesis and storage increased in schizophrenia

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What is associated with the increased dopamine secretion in the striatum in schizophrenia

Reduced glutamate function in frontal lobes

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What symptoms are reduced frontal glutamate levels associated with

Negative symptoms

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What symptoms are increased striatal dopamine levels associated with

Positive symptoms

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What is glutamate dysfunction particularly associated with in schizophrenia

Cognitive symptoms

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What does hypoactivity in PFC in schizophrenia lead to

Increased DA release in Nacc

look at pathway diagram in notes

Drugs associated with psychosis influence via dopamine, serotonin and glutamate function

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

Most likely environmental determinant of transition to psychosis in 2018

Cannabis

Affective psychosis

Bipolar disorder
Depressive psychosis
Schizoaffective disorder

‘Organic’ psychosis(just know a few examples)

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
Personality disorder

Target of antipsychotic drugs in psychosis treatment

- Dopamine dysregulation

Alternative treatment for psychosis

- CBT

Which drug has the greatest efficacy in resistant cases of psychosis

- Clozapine | - Treatment benefit usually clinically evident by 2 weeks

D2 dopamine antagonist effects

- Parkinsonism - Tardive dyskinesia - Raised prolactin

Alpha-1 norepinephrine antagonist effect

- Postural hypotension

H1 histamine antagonist effect

- Sedation | - Weight gain

M1 cholinergic antagonism

Constipation, Urinary retention, Blurred vision, Confusion etc (clozapine only): Saliva overproduction Also cardiac conduction delay in some

Typical antipsychotics

- Haloperidol | - Chlopromazine

Atypical antipsychotics

``` · Amisulpride · Aripiprazole · Clozapine · Risperidone · Olanzapine · Quetiapine · Lurasidone ```

Long acting injections(up to monthly administration) - antipsychotics

· Depixol · Clopixol · Piportil · Paloperidone(risperidone) · Olanzapine · Aripiprazole

Extrapyramidal side effects of typical antipsychotics

Parkinsonian symptoms Dystonia Akithisia Tardive dyskinesia

Cardiac side effects of typical antipsychotics

- Hypotension - Arrhythmias - Temperature dysregulation - Neuroleptic malignant syndrome

Anticholinergic side effects of typical antipsychotics

- Weight gain(less than atypicals) | - Raised prolactin(galactorrhoea, decrease in sexual function, osteoporosis)

Less frequent effects of typical(old) antipsychotics

Less frequently - Jaundice - Lens opacities - Skin discolouration - Blood dyscrasias

Primary receptors affected by atypical(new) antipsychotics

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

Atypical(new) antipsychotics that cause sedation

- Olanzapine - Clozapine - Quetiapine (least for aripiprazole)

Atypical(new) antipsychotics that cause metabolic effects

- Weight gain, glucose intolerance, increase in triglycerides caused by olanzapine/clozapine more than othersl least for aripiprazole

Atypical(new) antipsychotics that cause raised prolactin effects

- Galactorrhoea, decrease in sexual function, osteoporosis(risperidone, amisulpride)

Cardiac effects of atypical(new) antipsychotics

- Hypotension(quetiapine) arrhythmias(less than typicals), neutropaenia with clozapine in 1% hence requires regular blood monitoring

Nice regulations 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

How is clozapine administered

- Oral medication taken daily

What is monitored in clozapine administration

- Neutrophil count - Neutropaenia in approximately 1% of cases but progression slow so ceasing medication significantly reduces risk - Slow titration to optimal dose with mintoring of pulse, BP and neutrophil count

Common side effects of clozapine

- Sedation, weight gain, dribbling common | - Little parkinsonian effects or tardive dyskinesia

Features of electroconvulsive treatment

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

Features of metabolic syndrome

• 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