(PM3B) Psychosis & Schizophrenia Flashcards

1
Q

What is psychosis?

A

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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2
Q

What is split personality a symptom of?

A

NOT schizophrenia

Multiple personality disorder

Very rare

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3
Q

Describe the aetiology of schizophrenia.

A

Onset – adolescence/ early adulthood

~1% lifetime risk

Higher incidence in lower socioeconomic groups

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4
Q

What role do genetics play in schizophrenia?

A

No single gene responsible (multiple which can increase risk)

Tends to be genetic

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5
Q

How is it known that schizophrenia is partly inherited?

A

Studies on identical twins

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6
Q

If identical twins are raised separately and one of them develops schizophrenia, what is the likelihood the other isolated twin will also develop this?

A

50%

1 in 2

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7
Q

If fraternal twins are raised separately and one of them develops schizophrenia, what is the likelihood the other isolated twin will also develop this?

A

12.5%

1 in 8

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8
Q

What neuropathological changes can be observed?

A

(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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9
Q

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

A

(1) Orbitofrontal cortex

(2) Amygdala

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10
Q

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

A

Ventromedial prefrontal cortex

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11
Q

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

A

Mesolimbic pathway

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12
Q

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

A

(1) Mesocortical

(2) Prefrontal cortex

(3) Nucleus accumbens (rewards circuits)

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13
Q

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

A

Dorsolateral prefrontal cortex

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14
Q

What are some positive symptoms of schizophrenia?

A

(1) Delusions

(2) Hallucinations

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15
Q

What are some negative symptoms of schizophrenia?

A

(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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16
Q

What are some inherited genetic factors of schizophrenia?

A

(1) Increased risk in families when 1 member is affected

(2) Susceptibility with certain genes – e.g. neuregelin 1

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17
Q

What is the significance of the neuregelin 1 gene?

A

Increases susceptibility of schizophrenia development

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18
Q

What are some environmental factors which may increase the susceptibility of developing schizophrenia?

A

(1) Birth complications

(2) Viral infection

(3) Immigration

(4) Drug misuse

(5) Inner cities

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19
Q

With regard to schizophrenia, what is the neurodevelopmental model?

A

Poor environment/ genetic factors

Lead to changes in brain development

Contribute to risk

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20
Q

What is the dopamine hypothesis?

A

Role of onset of schizophrenia

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21
Q

How is dopamine produced?

A

In dopaminergic neurones

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22
Q

What does dopamine bind to?

A

Dopamine receptors

D1-D5

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23
Q

What is the role of COMT in the synaptic cleft?

A

Breakdown of dopamine

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24
Q

What is the function of dopamine autoreceptors (D2)?

A

Is a presynaptic autoreceptor

Prevents the release of further dopamine

Negative feedback mechanism

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25
Q

Where can dopamine autoreceptors (D2) be found?

A

(1) Presynaptic membrane

(2) Somatodendritic

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26
Q

What is the mesolimbic pathway?

A

Reward/ dopaminergic pathway

Begins with ventral tegmental area (VTA) + ends with nucleus accumbens

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27
Q

In schizophrenia, what is the effect of the mesolimbic pathway?

A

Dopamine pathways are hyperactive

Release too much dopamine

Leads to positive symptoms

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28
Q

In schizophrenia, what is the effect of the mesocortical dopaminergic pathway?

A

Hypoactivity

Releasing too little dopamine

Selective neural degeneration of mesocortical dopaminergic production

Leads to negative symptoms

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29
Q

What is the cause of positive symptoms in schizophrenia?

A

Mesolimbic dopamine pathway

Dopamine (reward) pathway

Too much dopamine

30
Q

What is the cause of negative symptoms in schizophrenia?

A

Mesocortical dopamine pathway

Dopamine (reward) pathway

Too little dopamine

31
Q

With regard to schizophrenia, what is the glutamine hypothesis?

A

A novel hypothesis

Based the first psychopharmacological agents on it

Revision of glutamatergic transmission

32
Q

What are some of the key glutamatergic pathways in the brain?

A

(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

33
Q

What is PCP?

A

Phencyclinide

Drug that induces psychosis

34
Q

What are the effects of ketamine or PCP binding to NMDA-R?

A

Prevention of glutamate-mediated excitation

Hypofunction of this receptor is a possible mechanism for schizophrenia pathogenesis

35
Q

What types of symptoms can NMDA-R inhibition (hypofunction) lead to?

A

Both positive + negative

Depending on whether those NMDA-R receptors are in excitatory or inhibitory neurones

36
Q

What is the serotonin hypothesis?

A

Increased cortical seratoninergic tone

Leads to reduced dopamine secretion downstream

37
Q

What is the another term for the negative symptoms of schizophrenia?

A

Inhibited/ withdrawn

38
Q

What is another term for the positive symptoms of schizophrenia?

A

Disinhibited

39
Q

How are symptoms of schizophrenia diagnosed?

A

Purely psychiatric

No biomarkers/ clinical signs

40
Q

What may some observations of schizophrenia symptoms be?

A

(1) Reduced speech

(2) Poor grooming

(3) Limited eye-contact

41
Q

What may some consultations regarding schizophrenia highlight?

A

(1) Reduced emotional responsiveness

(2) Reduced interest

(3) Reduced social drive

42
Q

How may symptoms of schizophrenia change with time?

A

Progressively more negative symptoms compared to positive symptoms

43
Q

When do the positive symptoms of schizophrenia begin?

A

Acute phase of schizophrenia

44
Q

What is the prodromal phase of schizophrenia?

A

Beginning of initial symptoms

Some negative symptoms present

No positive symptoms present

45
Q

What type of schizophrenia symptoms are predominantly present in the chronic phase?

A

Negative symptoms (increasing)

Positive symptoms less common + decreasing

46
Q

What are some prognostic signs for an isolated episode of schizophrenia?

A

(1) No family history

(2) Stable personality (prior to episode)

(3) Acute onset

(4) Emotional responses preserved

(5) Early diagnosis + treatment

47
Q

What are some prognostic signs for a chronic (persistent) schizophrenia diagnosis?

A

(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

48
Q

What does delayed diagnosis and treatment of a schizophrenic episode increase likelihood of?

A

Persistent/ chronic schizophrenia

49
Q

What are the key aims of treatment in schizophrenia?

A

(1) Control acute attacks

(2) Resolution of social/ domestic factors

(3) Rehabilitate the patient

(4) Begin long-term maintenance therapy (if required)

50
Q

What are some examples of D2 antagonists?

A

(1) Antipsychotics
- Haloperidol
- Chlorpromazine

51
Q

What is the role of D2 antagonists in schizophrenia?

A

Treatment of positive symptoms

52
Q

How do D2 antagonists work in reducing positive symptoms of schizophrenia?

A

Reduce mesolimbic hyperactivity

53
Q

What is a downside of D2 antagonists for schizophrenia treatment?

A

Although they reduce positive symptoms

Can increase negative symptoms
- Reduces mesocortical dopaminergic tone

54
Q

What are extrapyramidal symptoms of schizophrenia?

A

Most common category of side effects

Associated with antipsychotic use

Manifestation of movement disorders

55
Q

What is acute dystonia?

A

Neck/ spine spasm

Neck/ jaw/ larynx rigidity

Oculogyric crisis – spasmodic movement of the eyeballs

56
Q

What is pseudo-parkinsonism?

A

Dyskinesia

Dystonia

Rigidity/ tremor/ bradykinesia

57
Q

What is akathisia?

A

Psychomotor restlessness

Agitation

Inability to sit still

58
Q

What is tardive dyskinesia?

A

Abnormal face/ mouth/ jaw movement

Lipsmacking/ grimacing/ tongue protrusion

Body writhing

59
Q

What is prolactinaemia?

A

Side effect of schizophrenia

Due to blocking of D2 receptors on prolactin producing cells

Leads to increased production of prolactin

60
Q

What can happen to the patient before the optimal level (plateau) of antipsychotic effect has been reached?

A

(1) Extrapyramidal effects

(2) Prolactinaemia

61
Q

What are some common side effects of blockage of M1 receptors?

A

(1) Dry mouth
(2) Increased risk of mouth ulcers

62
Q

What effect does reducing the mesolimbic dopamine pathway hyperactivity have on schizophrenia?

A

Reduces positive symptoms

Better control with fewer extrapyramidal side effects

63
Q

What effect, on schizophrenia, does blockage of serotonin (5HT2A) receptors in the cortex have?

A

(1) Increased dopamine secretion downstream

(2) Reduces extrapyramidal symptoms

(3) Reduces prolactinaemia prevalence

64
Q

What is the purpose of blockage of serotonin (5HT2A) receptors, with regard to schizophrenia?

A

Reduces effective antipsychotic threshold

To reduce prevalence of extrapyramidal symptoms + prolactinaemia

65
Q

Which drugs bind to the 5HT1B receptor?

A

(1) Olanzapine

(2) Clozapine

(3) Asenapine

66
Q

What are some side effects of D2 antagonists specifically?

A

(1) Weight gain

(2) Diabetes

(3) Increased smoking – as with schizophrenia

(4) Metabolic syndrome

67
Q

What is metabolic syndrome?

A

Combination of diabetes, high blood pressure (hypertension) and obesity

68
Q

What general types of antipsychotics are there?

A

(1) 1st generation – typical

(2) 2nd generation –atypical

69
Q

What type of antipsychotic are D2 receptor antagonists, 5HT antagonists and dopamine partial agonists?

A

Atypical

2nd generation

70
Q

Following an acute attack of schizophrenia, what is the treatment?

A

12-24 months follow-up treatment

~75% relapse

71
Q

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

A

No association with schizophrenia

Association with psychosis (acute episodes)