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Psychiatry > Neurobiology of Schizophrenia > Flashcards

Neurobiology of Schizophrenia Flashcards

1
Q

What is the genetic influence of schizophrenia?

A

Shows 78% heritability and polygenetic inheritance

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2
Q

What are the risk factors for schizophrenia?

A

2nd trimester viral illness, pre-eclampsia, foetal hypoxia, emergency Caesarian
Risk of schizophrenia increased 50% by childhood viral CNS infection

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3
Q

What drugs are associated with schizophrenia?

A

Psychosis risk increased by amphetamines, cocaine, cannabis and novel psychoactive substances

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4
Q

How may certain drugs cause schizophrenia?

A

In predisposed individuals, drug use may precipitate an episode and worsen overall prognosis

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5
Q

What are some brain features in schizophrenic patients with poor prognosis?

A

Reduced frontal lobe volume, reduced frontal lobe grey matter and enlarged lateral ventricle volume

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6
Q

What areas of the brain have subtle grey matter reduction in schizophrenic patients?

A

Temporal cortex = especially superior temporal cortex
Medial temporal lobe = especially hippocampus
Less so in orbitofrontal cortex, parietal cortex and basal ganglia

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7
Q

What are some features of brain abnormalities that occur in patients with schizophrenia?

A

Abnormalities present early in illness and likely premorbid

Some evidence from DTI for white matter abnormalities

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8
Q

What causes grey matter abnormalities in schizophrenia?

A

Due to reduced arborisation = likely progressive in the initial years of illness

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9
Q

When do environmental risk factors act in patients with schizophrenia?

A

When in utero or early childhood

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10
Q

What is present in children who go on to develop schizophrenia?

A

Have identifiable impaired behaviour, motor and intellectual development from infancy

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11
Q

What are some features of the ventricular enlargement that can occur in schizophrenia?

A

Often present at diagnosis and only progresses early in presentation

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12
Q

What is the dopamine hypothesis?

A

Drugs which release dopamine in the brain or D2 receptor agonists produce a psychotic state in man

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13
Q

What is an example of a drug which makes schizophrenia worse?

A

Amphetamine

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14
Q

What are dopamine receptor antagonists used for?

A

To treat the symptoms of schizophrenia

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15
Q

What are the different dopamine pathways?

A 
Tuberoinfundibular = controls prolactin release 
Mesolimbic/cortical = motivation and reward system
Nigrostriatal = extrapyramidal motor system
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16
Q

What are some features of the D1 receptor?

A

Most abundant receptor type

Found in neostriatum, cerebral cortex, olfactory tubercle and nucleus accumbens

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17
Q

What are some features of the D2 receptor?

A

Fairly widespread and also found in pituitary gland

Found in neostriatum, olfactory tubercle and nucleus accumbens

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18
Q

What does subcortical dopamine hyperactivity lead to?

A

Psychosis

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19
Q

What is the basis of the glutamatergic hypothesis?

A

Altered NMDA receptor subunit expression

20
Q

What is the serotonergic hypothesis?

A

Abnormalities in serotonin 2A binding potential in the frontal cortex index significantly smaller in schizophrenics

21
Q

What is the role of dysbindin?

A

Essential for adaptive neural plasticity

22
Q

What is neuregulin?

A

Signalling protein that mediates cell-cell interactions and plays critical role in growth and development of multiple organ systems

23
Q

What is DISC-1 involved in?

A

Neurite outgrowth and cortical development through its interactions with other proteins

24
Q

What are some examples of typical antipsychotics?

A

Chlorpromazine, thioridazine, fluphenazine, haloperidol, zuclopentixol

25
Q

How do typical antipsychotics work?

A

Mainly through inhibition of D2 receptor

26
Q

What defines atypical antipsychotics?

A

Less likely to induce extrapyramidal side effects
High 5-HT2A to D2 ratio
Better efficacy against negative symptoms
Effective in patients unresponsive to typical drugs

27
Q

What are some examples of atypical antipsychotics?

A

Olanzapine, risperidone, quetiapine, clozapine, aripiprazole, amisulpride, lurasidone

28
Q

What causes a D2 blockade?

A

Antipsychotics block D2 receptors in the nigrostriatum causing Parkinsonism = takes days-months

29
Q

What are some side effects of antipsychotics?

A

Acute dystonic reaction, parkinsonism, akathisia, tardive dyskinesia, hyperprolactinaemia, metabolic syndrome, histamine/alpha adrenergic/muscarinic blockade

30
Q

What is akathisia?

A

Internal restlessness = patients may complain of feeling need to constantly move

31
Q

What is tardive dyskinesia?

A

Repetitive involuntary purposeless movements (e.g grimacing, lip smacking) = normally takes years to develop, may continue after treatment stops

32
Q

Why does hyperprolactinaemia occur due to antipsychotic use?

A

Secretion of prolactin from pituitary is under inhibitory control by dopamine

33
Q

What do psychotomimetic drugs with high affinity for 5-HT2 receptors cause?

A

Hallucinations and thought disturbance

34
Q

What is the link between 5-HT2A receptor and schizophrenia?

A

There is some evidence of reduced 5-HT2A receptor binding in people at risk of schizophrenia

35
Q

What do lots of atypical antipsychotics cause?

A

5-HT2A antagonism = pure 5-HT2A antagonists are not antipsychotic however

36
Q

What are some features of the metabolic syndrome caused by antipsychotics?

A

Effect on weight gain may partially involve antagonists or inverse agonist activity at 5-HT2C receptors
Much more metabolic syndrome from atypicals

37
Q

What effect do interactions of antipsychotics at specific serotonin receptors have?

A

May modulate aspects of the immune response and inflammation

38
Q

What are some features of using antihistamines?

A

Cause sedation and increased appetite
May reduce nausea and vomiting
Newer antihistamines aren’t sedating because they don’t cross the BBB

39
Q

What are the effects of an alpha adrenergic blockade?

A

Reducing alpha1-adrenergic activity of blood vessels may cause hypotension and interrupts baroreceptor response = dizziness, lightheadedness, orthostatic or postural hypotension

40
Q

What are the effects of a muscarinic blockade?

A

Muscarinic receptors are target of PNS = dry mouth, constipation, urinary retention, sedation, confusion

41
Q

What should you consider when choosing an antipsychotic?

A

No real difference in efficacy (apart of clozapine)
Consider previous use of antipsychotics
Consider pre-existing comorbidities and side effects

42
Q

What patients may benefit from giving antipsychotics as a long acting depot IM injection?

A

Detained patients who lack insight and won’t take oral medication regularly
Informal patients who would prefer infrequent injections or who struggle with oral compliance

43
Q

When is clozapine indicated?

A

When there has been inadequate response to at least 2 other antipsychotics, usually both an atypical and typical

44
Q

What are some side effects of clozapine?

A

Causes more sedation and metabolic syndrome than any other antipsychotic
Agranulocytosis and myocarditis

45
Q

What are some features of the agranulocytosis caused by clozapine?

A

Intermediary metabolite accelerates apoptosis

Do full blood count in any patient on clozapine with a sore throat

46
Q

How often should a full blood count be done for patients on clozapine?

A

Weekly for the first six months, fortnightly for the next months and every four weeks thereafter
Do full blood count 1 month after cessation of drug

47
Q

How do you identify myocarditis on an ECG?

A

Non-specific ST segment changes

Psychiatry (36 decks)

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