(PM3B) Psychosis & Schizophrenia Flashcards
What is psychosis?
Syndrome (a set of symptoms)
- Delusions/ hallucination/ disorganised speech or behaviour/ distortion of reality
Can be associated with Alzheimer’s disease, depression, cognitive disorders + mania
Define syndrome.
A set of symptoms
What is the principle symptom of schizophrenia?
Psychosis
What is split personality a symptom of?
NOT schizophrenia
Multiple personality disorder
Very rare
Describe the aetiology of schizophrenia.
Onset – adolescence/ early adulthood
~1% lifetime risk
Higher incidence in lower socioeconomic groups
What role do genetics play in schizophrenia?
No single gene responsible (multiple which can increase risk)
Tends to be genetic
How is it known that schizophrenia is partly inherited?
Studies on identical twins
If identical twins are raised separately and one of them develops schizophrenia, what is the likelihood the other isolated twin will also develop this?
50%
1 in 2
If fraternal twins are raised separately and one of them develops schizophrenia, what is the likelihood the other isolated twin will also develop this?
12.5%
1 in 8
What neuropathological changes can be observed?
(1) Enlarged ventricles
(2) Reduced temporal lobe volume – post-mortem
(3) Reduce cerebral blood flow -> reduced frontal function
(4) Non-progressive
Which area(s) of the brain is/ are responsible for aggressive symptoms of schizophrenia?
(1) Orbitofrontal cortex
(2) Amygdala
Which area(s) of the brain is/ are responsible for affective symptoms of schizophrenia?
Ventromedial prefrontal cortex
Which area(s) of the brain is/ are responsible for positive symptoms of schizophrenia?
Mesolimbic pathway
Which area(s) of the brain is/ are responsible for negative symptoms of schizophrenia?
(1) Mesocortical
(2) Prefrontal cortex
(3) Nucleus accumbens (rewards circuits)
Which area(s) of the brain is/ are responsible for cognitive symptoms of schizophrenia?
Dorsolateral prefrontal cortex
What are some positive symptoms of schizophrenia?
(1) Delusions
(2) Hallucinations
What are some negative symptoms of schizophrenia?
(1) Apathy
(2) Anhedonia – inability to feel pleasure in normally pleasurable activities
(3) Cognitive blunting
(4) Neuroleptic dysphoria – unpleasant changes of thinking
What are some inherited genetic factors of schizophrenia?
(1) Increased risk in families when 1 member is affected
(2) Susceptibility with certain genes – e.g. neuregelin 1
What is the significance of the neuregelin 1 gene?
Increases susceptibility of schizophrenia development
What are some environmental factors which may increase the susceptibility of developing schizophrenia?
(1) Birth complications
(2) Viral infection
(3) Immigration
(4) Drug misuse
(5) Inner cities
With regard to schizophrenia, what is the neurodevelopmental model?
Poor environment/ genetic factors
Lead to changes in brain development
Contribute to risk
What is the dopamine hypothesis?
Role of onset of schizophrenia
How is dopamine produced?
In dopaminergic neurones
What does dopamine bind to?
Dopamine receptors
D1-D5
What is the role of COMT in the synaptic cleft?
Breakdown of dopamine
What is the function of dopamine autoreceptors (D2)?
Is a presynaptic autoreceptor
Prevents the release of further dopamine
Negative feedback mechanism
Where can dopamine autoreceptors (D2) be found?
(1) Presynaptic membrane
(2) Somatodendritic
What is the mesolimbic pathway?
Reward/ dopaminergic pathway
Begins with ventral tegmental area (VTA) + ends with nucleus accumbens
In schizophrenia, what is the effect of the mesolimbic pathway?
Dopamine pathways are hyperactive
Release too much dopamine
Leads to positive symptoms
In schizophrenia, what is the effect of the mesocortical dopaminergic pathway?
Hypoactivity
Releasing too little dopamine
Selective neural degeneration of mesocortical dopaminergic production
Leads to negative symptoms
What is the cause of positive symptoms in schizophrenia?
Mesolimbic dopamine pathway
Dopamine (reward) pathway
Too much dopamine
What is the cause of negative symptoms in schizophrenia?
Mesocortical dopamine pathway
Dopamine (reward) pathway
Too little dopamine
With regard to schizophrenia, what is the glutamine hypothesis?
A novel hypothesis
Based the first psychopharmacological agents on it
Revision of glutamatergic transmission
What are some of the key glutamatergic pathways in the brain?
(1) Cortico-brainstem glutamatergic projection
(2) Cortico-striatal glutamatergic pathway
(3) Thalami-cortical glutamatergic pathway
(4) Ventral hippocampus to nucleus accumbens
(5) Cortico-thalamic glutamatergic pathway
(6) Cortico-cortical glutamatergic pathway
(7) Intracortical with GABAergic coordination
What is PCP?
Phencyclinide
Drug that induces psychosis
What are the effects of ketamine or PCP binding to NMDA-R?
Prevention of glutamate-mediated excitation
Hypofunction of this receptor is a possible mechanism for schizophrenia pathogenesis
What types of symptoms can NMDA-R inhibition (hypofunction) lead to?
Both positive + negative
Depending on whether those NMDA-R receptors are in excitatory or inhibitory neurones
What is the serotonin hypothesis?
Increased cortical seratoninergic tone
Leads to reduced dopamine secretion downstream
What is the another term for the negative symptoms of schizophrenia?
Inhibited/ withdrawn
What is another term for the positive symptoms of schizophrenia?
Disinhibited
How are symptoms of schizophrenia diagnosed?
Purely psychiatric
No biomarkers/ clinical signs
What may some observations of schizophrenia symptoms be?
(1) Reduced speech
(2) Poor grooming
(3) Limited eye-contact
What may some consultations regarding schizophrenia highlight?
(1) Reduced emotional responsiveness
(2) Reduced interest
(3) Reduced social drive
How may symptoms of schizophrenia change with time?
Progressively more negative symptoms compared to positive symptoms
When do the positive symptoms of schizophrenia begin?
Acute phase of schizophrenia
What is the prodromal phase of schizophrenia?
Beginning of initial symptoms
Some negative symptoms present
No positive symptoms present
What type of schizophrenia symptoms are predominantly present in the chronic phase?
Negative symptoms (increasing)
Positive symptoms less common + decreasing
What are some prognostic signs for an isolated episode of schizophrenia?
(1) No family history
(2) Stable personality (prior to episode)
(3) Acute onset
(4) Emotional responses preserved
(5) Early diagnosis + treatment
What are some prognostic signs for a chronic (persistent) schizophrenia diagnosis?
(1) Family history
(2) Disturbed personality (prior to episode)
(3) Inability to form relationships
(4) Poor social adjustment
(5) Insidious onset (gradual + subtle)
(6) Loss of initiative/ drive
(7) Delayed diagnosis + treatment
What does delayed diagnosis and treatment of a schizophrenic episode increase likelihood of?
Persistent/ chronic schizophrenia
What are the key aims of treatment in schizophrenia?
(1) Control acute attacks
(2) Resolution of social/ domestic factors
(3) Rehabilitate the patient
(4) Begin long-term maintenance therapy (if required)
What are some examples of D2 antagonists?
(1) Antipsychotics
- Haloperidol
- Chlorpromazine
What is the role of D2 antagonists in schizophrenia?
Treatment of positive symptoms
How do D2 antagonists work in reducing positive symptoms of schizophrenia?
Reduce mesolimbic hyperactivity
What is a downside of D2 antagonists for schizophrenia treatment?
Although they reduce positive symptoms
Can increase negative symptoms
- Reduces mesocortical dopaminergic tone
What are extrapyramidal symptoms of schizophrenia?
Most common category of side effects
Associated with antipsychotic use
Manifestation of movement disorders
What is acute dystonia?
Neck/ spine spasm
Neck/ jaw/ larynx rigidity
Oculogyric crisis – spasmodic movement of the eyeballs
What is pseudo-parkinsonism?
Dyskinesia
Dystonia
Rigidity/ tremor/ bradykinesia
What is akathisia?
Psychomotor restlessness
Agitation
Inability to sit still
What is tardive dyskinesia?
Abnormal face/ mouth/ jaw movement
Lipsmacking/ grimacing/ tongue protrusion
Body writhing
What is prolactinaemia?
Side effect of schizophrenia
Due to blocking of D2 receptors on prolactin producing cells
Leads to increased production of prolactin
What can happen to the patient before the optimal level (plateau) of antipsychotic effect has been reached?
(1) Extrapyramidal effects
(2) Prolactinaemia
What are some common side effects of blockage of M1 receptors?
(1) Dry mouth
(2) Increased risk of mouth ulcers
What effect does reducing the mesolimbic dopamine pathway hyperactivity have on schizophrenia?
Reduces positive symptoms
Better control with fewer extrapyramidal side effects
What effect, on schizophrenia, does blockage of serotonin (5HT2A) receptors in the cortex have?
(1) Increased dopamine secretion downstream
(2) Reduces extrapyramidal symptoms
(3) Reduces prolactinaemia prevalence
What is the purpose of blockage of serotonin (5HT2A) receptors, with regard to schizophrenia?
Reduces effective antipsychotic threshold
To reduce prevalence of extrapyramidal symptoms + prolactinaemia
Which drugs bind to the 5HT1B receptor?
(1) Olanzapine
(2) Clozapine
(3) Asenapine
What are some side effects of D2 antagonists specifically?
(1) Weight gain
(2) Diabetes
(3) Increased smoking – as with schizophrenia
(4) Metabolic syndrome
What is metabolic syndrome?
Combination of diabetes, high blood pressure (hypertension) and obesity
What general types of antipsychotics are there?
(1) 1st generation – typical
(2) 2nd generation –atypical
What type of antipsychotic are D2 receptor antagonists, 5HT antagonists and dopamine partial agonists?
Atypical
2nd generation
Following an acute attack of schizophrenia, what is the treatment?
12-24 months follow-up treatment
~75% relapse
Is schizophrenia the same as psychosis?
No
Psychosis is a symptom of schizophrenia
Schizophrenia is NOT psychosis
What association is there between cannabis use and schizophrenia or psychosis?
No association with schizophrenia
Association with psychosis (acute episodes)
