Schizophrenia & Antipsychotics

Question 1

Shcizophrenia age of onset:

Answer 1

• Men 20-28 Yrs
• Women 26-32 Yrs.

Age on onset = either diagnosis or first psychiatric episode

Question 2

Schizophrenia biological basis in brain:

Answer 2

Large ventricle spaces in brain - bigger in people with schizophrenia potentially due to brain shrinkage.

Question 3

Schizophrenia genetic risk factors:

Answer 3

It appears that multiple genes are involved in creating a predisposition to developing the disorder.

“Susceptibility genes”
KCNH2, DTNBP1, NRG1, DISC1, RGS4.

Question 4

Schizophrenia environmental risk factors

Answer 4

Prenatal problems, obstetric complications, urban/city birth, stressful life events, drug abuse

Question 5

Examples of positive symptoms:

something added to the persons personality

Answer 5

• Delusions
• Hallucinations
• Disorganized Speech

Question 6

Examples of negative symptoms:

Depression like symptoms, things taken away from personality

Answer 6

• Emotion
• Decreased motivation
• Interests
• Thought and Speech
• Pleasure

Question 7

Example of cognitive deficits in schizophrenia:

Answer 7

• Attention
• Working + Verbal Memory
• Executive Function

Question 8

Mood symptoms of schizophrenia:

Answer 8

• Depression/Anxiety
• Hostility/Aggression
• Suicide

Question 9

Positive symptoms hypothetically malfunctioning brain circuit.

Answer 9

Mesolimbic and striatal

Question 10

Negative symptoms hypothetically malfunctioning brain circuit.

Answer 10

Mesocortical/prefrontal cortex

Nucleus accumbent reward circuits

Question 11

Affective symptoms hypothetically malfunctioning brain circuit. :

Answer 11

Ventromedial prefrontal cortex

Question 12

Aggressive symptoms hypothetically malfunctioning brain circuit:

Answer 12

Orbitofrontal cortex

Amygldala

Question 13

Cognitive symptoms hypothetically malfunctioning brain circuit:

Answer 13

Dorsolateral prefrontal cortex

Question 14

What is DSM-V?

Answer 14

Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V)

Psychiatric Diagnoses are categorized by the DSM-V

Covers all mental health disorders for both children and adults

Question 15

Dopamine theory/treatment:

Answer 15

• Increased dopamine in subcortical pathways
• Psychotic Symptoms
• Agonists of Dopamine neurotransmission induce psychotic symptoms e.g. amphetamine

Antipsychotics are ANTAGONISTS at dopamine D2 receptors. Works by getting into the brain and compete with dopamine for the d2 receptor .

Question 16

Glutamate theory:

NMDA hypofunction

Answer 16

• NMDA receptor hypofunctional state induced by genetic and non-genetic factors instilled into the brain early in development triggers psychosis in adulthood
• Clinical Observations (Phencyclidine)
  People who take PCP and render their NMDA receptors hypofunctional not only experience positive symptoms such as delusions and hallucinations but also affective symptoms, such as blunted affect, negative symptoms, such as social withdrawal, and cognitive symptoms, such as executive dysfunction.

Question 17

Current treatments: 
Typical Antipsychotics (neuroleptics) examples and mode of action:

Answer 17

e. g. Haloperidol, Chlorpromazine
- High affinity for dopamine D2 receptors
- Effective against the +ve symptoms
- Ineffective against the -ve symptoms

Typicals (>Atypicals)
- cause motor control impairments, due to their increased blockade of Dopamine D2 receptors. Parkinsonian symptoms, Undesriable SE’s

Question 18

Atypical Antipsychotics examples:

Answer 18

e. g. Clozapine, Olanzapine, Resperidone
- Higher affinity for serotonin (5-HT2) than dopamine D2 receptors
- “Rich” pharmacology – dirty drugs
- Effective against the +ve symptoms
- Improved efficacy against -ve symptoms ??

Less motor impairments, Significant side-effects, e.g. Weight gain, Metabolic syndrome, Agranulocytosis

Question 19

4 major pathways of dopamine neurones:

Answer 19

1) Nigrostriatal pathway
2) Mesolimbic pathway
3) Mesocortical pathway
4) Tuberoinfundibular pathway

Question 20

Side effects of atypical antipsychotics:

Answer 20

Weight gain, dyslipidemia, CVD, diabetes, hyper glycemia, insulin resistance , EPS

Question 21

What is the window of occupancy:

Answer 21

• Window of occupancy between efficacy & Side effect
• Doses to reach these thresholds vary across antipsychotics

Need to block certain % of receptor to see efficacy. If you increase dose, you increase blockade of receptor – side effects i.e. 70-80% gives parkinsonian side effects

Question 22

Haloperidol SE’s:

Answer 22

High risk of extrapyramidal side effects however no weight gain

Question 23

Mechanisms of antipsychotic induced weight gain?

Answer 23

Not fully understood

Theories include antagonism of

• Histamine H1 receptors
• Serotonin 5HT2c receptors
• D2 receptors
• Affecting hormonally controlled systems e.g. leptin
• Marked individual variation implies importance of genetic factors
• Future genetic tests to identify individual susceptibility

Question 24

Managing weight gain in schizophrenia:

Answer 24

• Warn patients before starting high risk drugs
• Early hunger, snacking and early weight gain all predict long term weight gain
• Weight management - eat less move more

Non-pharmacological weight-management interventions should be a priority (particularly in the early stages of antipsychotic treatment).

Question 25

Other psychotic drugs for weight gain:

Answer 25

Greater risk of weight gain:

• TCA’s
• Mirtazapine
• Lithium
• Valproate
• Carbamazepine

Lower risk of weight gain:

• SSRI’s
• Duloxetine
• Agomelatine
• Lamotrigine