Schizophrenia (EL) (DONE)

Question 1

Overview

Answer 1

Affects about 1% of the population
Typically appears in early adulthood (18-30 years)
Chronic, debilitating and 5-10% of sufferers may commit suicide, chronic cases account for majority of long stay psychiatric patients
Progressive disintegration of personality and the relationship between self and world

Question 2

Definition

Answer 2

Kraepelin popularised the term dementia praecox to describe a condition where there is a breakdown of the personality at a relatively young age

Question 3

Diagnostic criteria

Answer 3

Four domains: positive, negative, mood, cognition
2 out of 5 characteristic symptoms must be present: delusions, hallucinations, disorganised speech, abnormal psychomotor behaviour, negative symptoms
For one month in the last 6, with social/occupational dysfunction

Question 4

Features of schizophrenia

Answer 4

Positive: delusions, hallucinations, disorganization
Negative: decreased emotional range, decreased expression of emotion, decreased motivation, decreased interests, decreased social drive, poverty of speech
Mood: depression
Cognitive: deficits in working memory, attention, executive function, problems with interpersonal relationships

Question 5

Positive symptoms

Answer 5

Abnormal by their presence, at least one of these must be present
Auditory hallucinations (voices repeating the individual’s thoughts)
Thought disorders- paranoid delusions e.g. they are reading and controlling my thoughts
Physical catatonia (maintaining strange posture for long periods)
Disorganised speech

Question 6

Negative symptoms

Answer 6

Abnormal by their absence, they can be true or reactive i.e. secondary to the positive symptoms
Catatonia
Emotional problems- social withdrawal, blunting of emotions, reduced speech

Question 7

Mood and cognition

Answer 7

Cognition- deficits in working memory, attention, executive function, problems with interpersonal relationships
Mood- affective symptoms- often depressed
Drug and alcohol abuse are common and can cause problems with diagnosis and treatment

Question 8

Aetiology

Answer 8

Both genetic and environmental factors contribute
CT (CTA or MRI) shows that there is loss of cortical neurones, reduced brain size, increased ventricular size (soft neurological signs). PET scans also show changes in the mesolimbic system.
It is considered neurodevelopmental rather than neurodegenerative

Question 9

Genetic link

Answer 9

In monozygotic twins with identical genes, if one twin develops schizophrenia, there is a 50% chance the other will also
Siblings of a schizophrenic show an increased risk of developing the disorder

Question 10

Areas of the brain involved

Answer 10

There are possible deviant connections between nerve cells- nerve sprouts called spines which form in childhood are 50% shorter and wider than usual
As a consequence information processing is impaired i.e. faulty circuitry is in place
Thalamus is pivotal in information processing
Imaging studies suggest that the volume of the thalamus is reduced in schizophrenia
Thalamic nuclei may be affected

Question 11

Dopaminergic theory

Answer 11

Amphetamine causes release of DA, producing a syndrome indistinguishable from schizophrenia in recreational users
D2 receptor agonists worsen the symptoms
Modest increase in D2 receptor density in the striatum

Question 12

Serotonergic theory

Answer 12

Lysergic acid diethylamide produces symptoms akin to schizophrenia
Many antipsychotics act at 5HT receptors as antagonists
5HT pathways and dopaminergic pathways are linked

Question 13

Serotonin involvement in schizophrenia

Answer 13

Post mortem studies: increase in 5HT transmission and 5HT transporter density in subcortical regions, decrease or no change in 5HT receptor density in prefrontal cortex

Question 14

Glutamatergic theory

Answer 14

Blockade of NMDA receptor channels by phencyclidine or ketamine produce schizophrenia-like symptoms
Glutamatergic neurones feed an excitatory input into striatal GABAergic neurones (inhibited by dopamine), so gating sensory input at the thalamic level

Question 15

NMDA antagonist stimulated hyperlocomotion

Answer 15

MK-801 and PCP induce a behavioural syndrome that includes hyperlocomotion, head weaving, body rolling, ataxia and reduced rearing in rats
Conventional and atypical APDs reduce MK-801 stimulated hyperlocomotion

Question 16

First generation antipsychotics

Answer 16

All reduce dopaminergic transmission (D2 antagonism)
Older first described drugs, D2 receptor antagonists, e.g. butyrphenones- haloperidol, phenothiazines- chlorpromazine/thiordizine
Reduce the positive symptoms of schizophrenia
Block DA inhibition of prolactin release (resultant increases in plasma levels leads to reduced gonadal function and lactation)
Higher risk of effects on nigrostriatal pathway causing extrapyramidal side effects

Question 17

Second generation antipsychotics

Answer 17

Thioridazine, sulpiride, risperidone and clozapine
5HT and dopamine receptor antagonism
Some e.g. risperidone reduce negative symptoms
Lower risk of extrapyramidal effects but associated with increase of metabolic side effects (weight gain, diabetes, headache)

Question 18

Third generation antipsychotics

Answer 18

Aripiprazole is only drug in this class currently licensed
Partial D2/D3 agonist
Partial 5HT1a agonist

Question 19

Four dopamine pathways

Answer 19

Mesolimbic (SCZ- increase in DA causes positive symptoms)
Mesocortical (SCZ- DA hypoactivity: negative, cognitive and affective symptoms)
Nigrostriatal (drugs- EPS and TD side effects)
Tuberohypophyseal (drugs- hyperprolactinaemia side effects)

Question 20

Effects of antipsychotics on prolactin secretion

Answer 20

Hypothalamic dopamine has an inhibitory influence on the output of the anterior pituitary (hypothalamic-pituitary axis)
NB depot injection is a good strategy when there are issues of compliance

Question 21

Drug side effects

Answer 21

Dyskinesias- DA function increases
Parkinsonism-like (akinesia)- DA function decerases
Tardive dyskinesias (facial muscles, takes months or years to occur)- DA function increases

Question 22

Antipsychotic side effects

Answer 22

Typical agents- stiffness, shakiness, slowed thinking, restlessness, BP changes, sex life problems
Atypical agents- sleepiness and slowness, weight gain, diabetes risk, BP changes, sex life problems, with higher doses or long term use stiffness and tardive dyskinesia
Clozapine- affects bone marrow and production of white blood cells making susceptibility to infection more likely (weight gain, constipation, over production of saliva, epilepsy risk)

Question 23

Neuroleptic malignant syndrome

Answer 23

Life threatening idiosyncratic reaction to antipsychotic drugs
Characterized by fever, altered mental status, muscle rigidity and autonomic dysfunction
Associated with virtually all neuroleptics, including newer atypical antipsychotics
Rare but requires prompt recognition to prevent significant morbidity and death
Treatment includes immediately stopping the offending agent and implementing supportive measures, as well as pharmacological interventions in more severe cases