Schizophrenia

Question 1

What is involved in schizophrenia?

Answer 1

Breakdown in the relation between:

Thought, emotion and behaviour

Leading to:

Faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation

Question 2

How is schizophrenia characterised?

Answer 2

Divorcement from reality in the mind (psychosis)

Question 3

What is the pathogensis?

Answer 3

Unknown

Question 4

Onset of schizophrenia

Answer 4

Late teens/ early 20s

Question 5

What percentage of people are effected?

Answer 5

1%

Question 6

What are the positive symptoms?

Answer 6

Hallucinations, delusions, paranoia, ideas of reference

Question 7

What are the negative symptoms?

Answer 7

Apathy, social withdrawal, anhedonia, emotional blunting, cognitive deficits, extreme inattentiveness or lack of motivation to interact with the environment

Question 8

Cognitive symptoms

Answer 8

Poor ‘executive functioning’ (understanding information and making decisions)

Difficulty in focussing & paying attention

Problems with ‘working memory’ (using information immediately and learning it)

Question 9

Features of schizophrenia

Answer 9

Positive 
Negative 
Cognitive 
Disorganisation 
Mood symptoms

Cause/Affect
Functional Impairments
Work
Interpersonal relationships
Self-care

Question 10

How is schizophrenia diagnosed?

Answer 10

DSM - American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders

Dependant on presence and duration of signs and symptoms (6 months) with one month of active symptoms

Such as significantly impaired by symptoms, difficulty working or with social relationships, compared to before

Also it can’t be explained by another diagnosis such as dug use or other mental illness

No blood test or biomarker

Question 11

What criteria must be met to diagnose?

Answer 11

At least 2 of:

• Delusions
• Hallucinations
• Disorganised speech
• Disorganised or catatoinic behaviour
• Negative symptoms

Question 12

Chance of complete recovery?

Answer 12

5-10%

Question 13

Patients’ suicide rate?

Answer 13

4.9% - 50 times higher than general population

Question 14

Factors affecting prognosis

Answer 14

• Age of onset (women 26-32 and men 20-28)
• Sex (1.4 x more frequently in males)
• Premorbid function
• Abrupt versus insidious onset
• Family history
• Duration of untreated illness
• Substance abuse

Question 15

Two classifications of antipsychotic drugs

Answer 15

Typical and atypical

Question 16

Typical antipsychotic drugs

Answer 16

• Phenothiazines (Chlorpromazine, Perphenazine, Fluphenazine, Thioridazine)
• Thioxanthenes (Flupenthixol, Clopenthixol)
• Butyrophenones (Haloperidol, Droperidol)

Question 17

Atypical antipsychotics

Answer 17

Clozapine
Risperidone
Sulpiride
Olanzapine
Aripiprazole

Question 18

Distinction between ‘typical’ and ‘atypical’

Answer 18

• Incidence of extrapyramidal side-effects (less in ‘atypical’ group)
• Efficacy in treatment-resistant group of patients
• Efficacy against negative symptoms.

Question 19

Typical Antipsychotics D receptor preference?

Answer 19

Blockade of D2 receptors specifically in the mesolimbic dopamine pathway

phenothiazines, thioxanthines and butyrophenones, show preference for D2 over D1 receptors

Question 20

Atypical Antipsychotics D receptor preference?

Answer 20

clozapine is relatively non-selective between D1 and D2, but has high affinity for D4

Question 21

Adverse Effects

Answer 21

Extrapyramidal motor disturbances:

• Parkinson-like symptoms
• Neuroleptic Malignant Syndrome
• Tardive dyskinesia (involuntary movements of face, tongue and limbs, appearing after months or years of antipsychotic treatment). (longterm blockade of nigrostriatal Dopamine pathway)
• Acute dystonias
• D2 receptors in mesolimbic system = reward system D2 blockade = ↓reward mechanism
• Seizures
• Cardiac toxicity Produce hypotension (primarily postural) by α-adrenergic blocked.

Question 22

What are the 4 dopaminergic pathways and their relevance antipsycohotic effects?

Answer 22

– The mesolimbic pathway (positive symptoms)
– The mesocortical pathway (negative symptoms)
– The nigrostriatal pathway (extrapyramidal symptoms and tardive dyskinesia)
– The tuberoinfundibular pathway (hyperprolactinemia)

Question 23

Where does the mesolimbic pathway start and end?

Answer 23

Ventral tegmental area(VTA) to the nucleus accumbens

Question 24

Where does the mesocortical pathway start and end?

Answer 24

Ventral tegmental area(VTA) to the prefrontal cortex

Question 25

Where does the nigrostriatal pathway start and end?

Answer 25

Substantia nigra to the striatum

Question 26

Where does the tuberohypophyseal pathway start and end?

Answer 26

Within the hypothalamus - tuberal region to the median eminence

Question 27

Mesolimbic pathway’s role

Answer 27

Key reward circuit, Detects rewarding stimuli. Activation tells individual to repeat the action. (motivation , positive reinforcement)
SCZ ↑ Dopamine = Positive symptoms
D2 antagonists reduce positive symptoms

Question 28

Mesocortical pathway’s role

Answer 28

important in motivation, emotion and executive functions .
SCZ ↓ Dopamine = Negative symptoms
Treatments aim to increase dopamine in this pathway

Question 29

Nigrostriatal dopamine pathway’s role

Answer 29

Related to neurological effects caused by D2 antagonists.

• contains about 80% of the brain’s dopamine.
• This pathway is involved in motor planning, dopaminergic neurons stimulate purposeful movement.
• D2 antagonism induces extrapyramidal symptoms

Question 30

Tuberohypophyseal pathway’s role?

Answer 30

D2 antagonism block dopamine in the tuberoinfundibular pathway, which can cause an increase in bloodprolactinlevels (hyperprolactinemia)

Question 31

Limitations of typical antipsychotics

Answer 31

• Approximately one-third of patients with schizophrenia fail to respond
• Limited efficacy against negative symptoms
• High proportion of patients relapse
• Side effects and compliance issues
• Atypical/New generation Antipsychotics are preferred for the treatment of various psychotic disorders.