Schizophrenia Basics

Question 1

when does schizophrenia emerge

Answer 1

adolescence and young adults

Question 2

what is the incidence rate of schizophrenia

Answer 2

1% population
6-17% family history
50% if affected twin

Question 3

what is the aetiology

Answer 3

genetic predisposition and environmental disturbances affect timing of fine tuning and synaptic stabilisation

Question 4

what is the pathology

Answer 4

reduced cortical grey matter
in human post mortem there is reduced dendritic length and spine density on pyramidal neurons

Question 5

positive symptoms

Answer 5

delusions
hallucinations
illusions
thought disorder
abnormal behaviour - aggressive

Question 6

negative symptoms

Answer 6

social withdrawal
disorganised speech (alogia)
flattened emotions
lack of drive (avolition)

Question 7

cognitive symptoms

Answer 7

executive function
learning and memory

Question 8

what is the dopamine hypothesis

Answer 8

DA (mesolimbic) hyperactivity causes positive symptoms of schizophrenia

Question 9

role of amphetamine

Answer 9

releases DA
induces stereotyped psychotic like symptoms in patients (paranoia/audit/visual hallucinations)

Question 10

L-DOPA in PD patients

Answer 10

induce psychosis

Question 11

typical antipsychotics

Answer 11

haloperidol
fluphenazine
chlorpromazine

they are D2 receptor antagonists

Question 12

affinity for D2 receptors

Answer 12

correlates with clinical potency of drugs

Question 13

D2 receptor antagonist side effects

Answer 13

sedation (H1 R antagonism)
hypotension (alpha adrenoreceptor antagonism)
anticholinergic side effects: blurred vision, dry mouth, constipation (mAChR antagonism)

Question 14

what is the mesolimbic pathway

Answer 14

ventral tegmental area (VTA) to limbic area (nucleus accumbent, amygdala, hippocampus)
controls emotions

Question 15

side effects from D2R blockade by typical antipsychotics

Answer 15

tuberoinfundibulnar pathway - increased prolactin secretion (gynaecomastia)
nigrostriatal pathway - extrapyramidal side effects (EPS): Parkinsonism, tardive dyskinesia

Question 16

atypical/second generation antipsychotics

Answer 16

clozapine
olanzapine
risperidone
quetiapine
aripiprazole
ziprasidone

Question 17

atypical antipsychotic receptor affinity

Answer 17

5HT2>D4>D2=D1=a-adrenoreceptor=mACh=H1
blocking D2/4 R in mesolimbic pathway combats positive symptoms

Question 18

D4 receptor location

Answer 18

mesolimbic pathway
not nigrostriatal

reduces incidence of EPS

Question 19

what causes negative symptoms

Answer 19

hypoactivity of the mesocortical pathway
5HT2A (Gq GPCR) blockade by atypical antipsychotics increase DA
reduced GABA disinhibits DA release

Question 20

mesocortical pathway

Answer 20

VTA to PFC

Question 21

similarities of both typical and atypical antipsychotics

Answer 21

15-30 hours
given orally or I-m 1-2 times a day
chemical lobotomy - too high dose

Question 22

advantages of atypical antipsychotics

Answer 22

reduces EPS
provides some relief of negative symptoms

Question 23

disadvantages of atypical antipsychotics

Answer 23

weight gain due to food cravings (5HT2 antagonism)
impairs glycaemic control causing insulin resistance, impaired glucose tolerance and type 2 diabetes
psychosis remains drug-refractory
no cognitive benefit (attention/learning/memory/executive function is still impaired)