Neurobiology of Schizophrenia Flashcards by Veronica Haughey

What is the genetic influence of schizophrenia?

Shows 78% heritability and polygenetic inheritance

How well did you know this?

Not at all

Perfectly

What are the risk factors for schizophrenia?

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

How well did you know this?

Not at all

Perfectly

What drugs are associated with schizophrenia?

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

How well did you know this?

Not at all

Perfectly

How may certain drugs cause schizophrenia?

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

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

Abnormalities present early in illness and likely premorbid

Some evidence from DTI for white matter abnormalities

How well did you know this?

Not at all

Perfectly

What causes grey matter abnormalities in schizophrenia?

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

How well did you know this?

Not at all

Perfectly

When do environmental risk factors act in patients with schizophrenia?

When in utero or early childhood

How well did you know this?

Not at all

Perfectly

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

Have identifiable impaired behaviour, motor and intellectual development from infancy

How well did you know this?

Not at all

Perfectly

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

Often present at diagnosis and only progresses early in presentation

How well did you know this?

Not at all

Perfectly

What is the dopamine hypothesis?

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

How well did you know this?

Not at all

Perfectly

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

Amphetamine

How well did you know this?

Not at all

Perfectly

What are dopamine receptor antagonists used for?

To treat the symptoms of schizophrenia

How well did you know this?

Not at all

Perfectly

What are the different dopamine pathways?

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

How well did you know this?

Not at all

Perfectly

What are some features of the D1 receptor?

Most abundant receptor type

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

How well did you know this?

Not at all

Perfectly

What are some features of the D2 receptor?

Fairly widespread and also found in pituitary gland

Found in neostriatum, olfactory tubercle and nucleus accumbens

How well did you know this?

Not at all

Perfectly

What does subcortical dopamine hyperactivity lead to?

Psychosis

How well did you know this?

Not at all

Perfectly

What is the basis of the glutamatergic hypothesis?

Altered NMDA receptor subunit expression

What is the serotonergic hypothesis?

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

What is the role of dysbindin?

Essential for adaptive neural plasticity

What is neuregulin?

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

What is DISC-1 involved in?

Neurite outgrowth and cortical development through its interactions with other proteins

What are some examples of typical antipsychotics?

Chlorpromazine, thioridazine, fluphenazine, haloperidol, zuclopentixol

How do typical antipsychotics work?

Mainly through inhibition of D2 receptor

What defines atypical antipsychotics?

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

What are some examples of atypical antipsychotics?

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

What causes a D2 blockade?

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

What are some side effects of antipsychotics?

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

What is akathisia?

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

What is tardive dyskinesia?

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

Why does hyperprolactinaemia occur due to antipsychotic use?

Secretion of prolactin from pituitary is under inhibitory control by dopamine

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

Hallucinations and thought disturbance

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

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

What do lots of atypical antipsychotics cause?

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

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

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

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

May modulate aspects of the immune response and inflammation

What are some features of using antihistamines?

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

What are the effects of an alpha adrenergic blockade?

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

What are the effects of a muscarinic blockade?

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

What should you consider when choosing an antipsychotic?

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

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

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

When is clozapine indicated?

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

What are some side effects of clozapine?

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

What are some features of the agranulocytosis caused by clozapine?

Intermediary metabolite accelerates apoptosis | Do full blood count in any patient on clozapine with a sore throat

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

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

How do you identify myocarditis on an ECG?

Non-specific ST segment changes