(PM3B) Psychosis & Schizophrenia Flashcards by Nikki Gurung

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

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What is split personality a symptom of?

NOT schizophrenia

Multiple personality disorder

Very rare

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Describe the aetiology of schizophrenia.

Onset – adolescence/ early adulthood

~1% lifetime risk

Higher incidence in lower socioeconomic groups

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What role do genetics play in schizophrenia?

No single gene responsible (multiple which can increase risk)

Tends to be genetic

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How is it known that schizophrenia is partly inherited?

Studies on identical twins

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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

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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

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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

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Which area(s) of the brain is/ are responsible for aggressive symptoms of schizophrenia?

(1) Orbitofrontal cortex

(2) Amygdala

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Which area(s) of the brain is/ are responsible for affective symptoms of schizophrenia?

Ventromedial prefrontal cortex

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Which area(s) of the brain is/ are responsible for positive symptoms of schizophrenia?

Mesolimbic pathway

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Which area(s) of the brain is/ are responsible for negative symptoms of schizophrenia?

(1) Mesocortical

(2) Prefrontal cortex

(3) Nucleus accumbens (rewards circuits)

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Which area(s) of the brain is/ are responsible for cognitive symptoms of schizophrenia?

Dorsolateral prefrontal cortex

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What are some positive symptoms of schizophrenia?

(1) Delusions

(2) Hallucinations

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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

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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

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What is the significance of the neuregelin 1 gene?

Increases susceptibility of schizophrenia development

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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

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With regard to schizophrenia, what is the neurodevelopmental model?

Poor environment/ genetic factors

Lead to changes in brain development

Contribute to risk

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What is the dopamine hypothesis?

Role of onset of schizophrenia

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How is dopamine produced?

In dopaminergic neurones

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What does dopamine bind to?

Dopamine receptors

D1-D5

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What is the role of COMT in the synaptic cleft?

Breakdown of dopamine

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What is the function of dopamine autoreceptors (D2)?

Is a presynaptic autoreceptor

Prevents the release of further dopamine

Negative feedback mechanism

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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

What association is there between cannabis use and schizophrenia or psychosis?

No association with schizophrenia Association with psychosis (acute episodes)