PH3113 - Psychiatric Disease and its Pharmacology 4

Question 1

What is the treatment for narcolepsy?

Answer 1

Modafinil
- first line
Methylphenidate
- second line
Modafinil with sodium oxybate
- third line
Antidepressants
- may improve sleep paralysis or hallucinations
- tri-cyclic antidepressants
- clomipramine
- selective serotonin reuptake inhibitors
Benzodiazepines
- short acting
- only in refractory cases

Question 2

What is the largest single disease burden in the UK?

Answer 2

Mental illness
- costs £105bn/year

Question 3

How many people suffer a mental health illness per year?

Answer 3

1 in 4 people

Question 4

What is the leading cause of death of men between 18 and 45 years old?

Answer 4

Suicide

Question 5

What is psychosis?

Answer 5

Symptom of the mind under severe distress
- lack of sleep
- physical illness
- induced by drugs
- psychiatric illness

During a period of psychosis, a person’s thoughts and perceptions are disturbed
- the individual may have difficulty understanding what is real and what is not

Question 6

What is the prevalence of schizophrenia?

Answer 6

Chronic, relapsing, severe mental illness affecting approximately 1% of the population
220,000 people in UK currently being treated
Appears in early adulthood
- 18 - 30 years
1:1 ratio M:F
Costs £11bn/year to society
Unemployment high
- 80 - 90%
Chronic, debilitating
- 5 - 10% of sufferers may commit suicide
- 25% never recover
- account for majority of long-stay psychiatric patients

Question 7

What is schizophrenia characterised by?

Answer 7

Prodrome
- social isolation
- loss of interest
Distortions of thinking and perception
- positive symptoms
Inappropriate or blunted affect and cognitive symptoms
- negative symptoms

Question 8

How is schizophrenia diagnosed?

Answer 8

Diagnosis (ICD-10) based on at least one of:
- thought interference
- delusions of control
- auditory hallucinations giving running commentary
- persistent delusions being completely reasonable

Or at least two of:
- hallucinations in any modality with delusions/overvalued ideas
- disorganised speech
- neologisms
- catatonic behaviour
- posturing
- stupor
- negative symptoms
- apathy
- paucity of speech
- incongruent emotional responses
- significant change in personal behaviour and personality

Duration of 1 month of greater

Question 9

What are delusions?

Answer 9

An unshakeable, false belief, based on a mistaken interpretation of reality inconsistent with the person’s cultural background

Question 10

What are hallucinations?

Answer 10

A perception in the absence of an external stimulus
- auditory
- running commentary
- voice or voices giving a description of a person’s actions
- command
- voice or voices giving instructions or orders
- thought interference
- broadcasting
- withdrawal
- interference
- visual
- olfactory
- tactile
- gustatory

Question 11

What are the negative symptoms of schizophrenia?

Answer 11

Blunted affect
- hard to express emotions
- movements
- tone of voice
- facial expression
Social withdrawal
Avolition
- lack of motivation
Poverty of speech
- not speaking
Cognitive deficits

Question 12

What is the aetiology of schizophrenia?

Answer 12

Biological factors
- genetics
- multifocal
- 50% inheritance in monozygotic twins
- obstetric complications
- neurochemical and structural abnormalities
- dopamine hypothesis
- glutamate hypothesis
- serotonin hypothesis
Environmental factors
- urban areas
- socioeconomic status
- drift hyprothesis
- seasonality of births
- viral
- melatonin
- migration
- 10 x prevalence in immigrant populations
- life events and background stressors
- cannabis and other drug use

Question 13

What is the dopamine theory in schizophrenia?

Answer 13

Increased mesolimbic dopamine transmission mediates positive symptoms of schizophrenia
- amphetamine increases dopamine transmission in mesolimbic cortex
- associated with positive symptoms
- antipsychotics are dopamine antagonists
Negative symptoms may result from reduced dopaminergic activity in the prefrontal cortex

Plasma prolactin is normal
- dopamine inhibits release
Levels of metabolites of dopamine are normal
Brain levels of dopamine are normal
Tyrosine hydroxylase or mono-amine oxidase levels are normal
Modest increase in D2-receptor density in the striatum

Question 14

What role does the mesolimbic pathway play in schizophrenia?

Answer 14

Excess activity implicated in
- positive symptom schizophrenia
- hallucinations
- delusions

Question 15

What role does the mesocortical pathway play in schizophrenia?

Answer 15

Diminished activity implicated in
- negative symptom schizophrenia
- restrictions in
- emotion
- thought
- speech
- pleasure and attention

Question 16

What is the serotonergic (5-HT) theory in schizophrenia?

Answer 16

No consensus in role of 5-HT
- LSD produces symptoms akin to schizophrenia
- cerebrospinal fluid (CSF) studies of 5-HT metabolites
- post-mortem studies in schizophrenia
- increase in 5-HT transmission and 5-HT transporter density in sub-cortical regions
- no change or decrease in cortical regions
- decrease or no change in 5-HT2 receptor density in pre-frontal cortex

Drug studies
- agonist studies
- administration of m-chlorophenylpiperazine (mCPP)
- a 5-HT partial agonist
- exacerbates symptoms in unmedicated schizophrenics
- no effect in healthy volunteers
- many antipsychotics act at 5-HT2 receptors as antagonists
- dampen down 5-HT receptors

Question 17

What is the role of glutamate in schizophrenia?

Answer 17

Abnormalities in glutamate activity may underlie other neurochemical changes
Recent imaging studies have revealed increased glutamatergic activity in patients unresponsive to antipsychotic treatment
- not dopaminergic

Question 18

What is the treatment for schizophrenia?

Answer 18

Assessment
- ruling out non-psychiatric causes of psychosis
- drugs
Psychological interventions
- psychoeducation
- CBT for psychosis
- voice hearing groups
- family work
Social interventions
- occupational therapy
- housing
- employment
- supported accommodation
Biological
- antipsychotic medication