CNS Disorders - Schizophrenia

Question 1

what are the positive symptoms of schizophrenia

Answer 1

hallucination - mainly auditory
though disorder
stereotyped behaviours

Question 2

what are the negative symptoms of schizophrenia

Answer 2

poverty of affect
temporal disorientation
cognitive impairment

Question 3

what is the evidence for a genetic cause of schizophrenia

Answer 3

high concordance in monozygotic twins of 48%

Question 4

what are potential psychosocial causes of schizophrenia

Answer 4

adolescent onset
stress
emotionally charged home environment
blunted cortisol responses

Question 5

what is the evidence to suggest that schizophrenia is not caused by structural brain damage

Answer 5

CAT/MRI scans show ventricular enlargement and decreased volume of temporal lobe
but no gliosis - so not neurodegenerative

Question 6

what are the cytoarchitectural abnormalities in a schizophrenic patient

Answer 6

decreased number of small neurones in superficial layer
increased number of large neurones in deeper layers

Question 7

what is the evidence for viral infection being a cause for schizophrenia

Answer 7

higher incidence of patients born in winter/spring
exposure of mother to virus during second trimester increases child’s risk to schizophrenia

Question 8

what are the sites of brain dysfunction during auditory hallucinations

Answer 8

decreased size of temporal lobes and enlarged ventricles

Question 9

in normal brains the left side of the brain has increased activity during verbal tasks - how is this affected by schizophrenia

Answer 9

this lateralisation is disrupted
dysfunction of dominant cerebral hemishpere

Question 10

what does diffusor tensor imaging of schizophrenia show

Answer 10

hypo-functionality of dorsal-lateral pre-frontal cortex

Question 11

what is the site of anti-psychotics and is also a brain dysfunction in schizophrenia

Answer 11

basal ganglia

Question 12

what is the dopamine hypothesis for symptoms of schizophrenia and what is the evidence for this

Answer 12

due to excess dopamine neurotransmission in the mesolimbic and mesocortical regions
no consistent evidence for this hypothesis

Question 13

chronic treatment of antipsychotics to rats was done to anaesthetise and record DA activity in rats, where specifically where they measuring DA activity

Answer 13

substantia nigra - SN
ventral tegmental area - VTA

Question 14

before any antipsychotic treatment outline the activity of VTA neurones compared to SN

Answer 14

VTA neurone activity is greater than SN neurone activity

Question 15

how did acute antipsychotic treatment affect the rats

Answer 15

increase in mesolimbic activity of VTA neurones
no change in mesocortical neurone activity

Question 16

how did chronic antipsychotic treatment affect the rats

Answer 16

mesolimbic VTA neurones become silent
still no change in mesocortical neurone activity

Question 17

so how does the study treating rats with antipsychotics explain the delayed onset effect of antipsychotics - chlorpromazine

Answer 17

blocks autoreceptor feedback which increases pre-synaptic activity - release of dopamine
but after a while this causes a depolarizing block in the neurone

Question 18

what is the effect of DA releasing neurones entering depolarizing block in the mesolimbic region

Answer 18

since there is no change in neurone activity in the mesocortical neurones from antipsychotic treatment - there is a relative increase in DA activity in the mesocortical region

Question 19

what are the typical antipsychotics

Answer 19

phenothiazines
thioxanthenes
butyrophenones

Question 20

what are the common side-effects of typical antipsychotics

Answer 20

weight gain
sedation
postural hypotension
atropine-like side-effects
hyperprolactinaemia

Question 21

what is the weight gain and sedation side-effects from antipsychotic use caused by

Answer 21

blockade of histamine receptors - antihistamines

Question 22

what is the postural hypotension side-effect from antipsychotic use caused by

Answer 22

blockade of alpha-adrenoceptors

Question 23

what is the hyperprolactinaemia side-effect of antipsychotic use caused by

Answer 23

blockade of D2 receptors

Question 24

what is a rare but lethal side-effect of antipsychotics

Answer 24

neuroleptic malignant syndrome

Question 25

why can antipsychotics produce Parkinson’s like syndrome

Answer 25

blocks dopamine receptors in the substantia nigra - which is involved in extra-parameter motor control

Question 26

what is a chronic disorder associated with antipsychotic use

Answer 26

Tardive dyskinesia

Question 27

what are the features of Tardive dyskinesia

Answer 27

purposeless, repetitive movement
irreversible

Question 28

what are the potential causes for Tardive dyskinesia

Answer 28

dopamine receptor super-sensitivity hypothesis
neuroleptic toxicity hypothesis
GABA hypothesis

Question 29

what are the advantages of clozapine and its major flaw

Answer 29

produces less sedation
lower incidence of movement disorders
treats negative symptoms

lethal anaemia - agranulocytosis

Question 30

what are the effects of clozapine on different receptors

Answer 30

dopamine D4 antagonist
5HT-2A antagonist
alpha-1 adrenoceptor antagonist
muscarinic receptor antagonist

Question 31

what is the genetic basis for the pathophysiology of schizophrenia

Answer 31

cortical dysfunction

Question 32

what are the genes implicated in schizophrenia

Answer 32

DISC-1
neuregulin
catechol-o-methyltransferase

Question 33

what are the features of Velocardio Facial Syndrome (VCFS)

Answer 33

deletion of 1.5-3 Mb in chromosome 22
increased incidence of psychiatric disorders including schizophrenia

Question 34

what mutation in which chromosome has a higher incidence in schizophrenic patients

Answer 34

deletion in chromosome 22

Question 35

function of catechol-o-methyltransferase (COMT)

Answer 35

metabolic enzyme for dopamine

Question 36

what are the features of DSIC-1

Answer 36

increased expression during neuronal development
expressed in cortical neurones
interacts with several proteins

Question 37

how does DISC-1 control neuronal proliferation

Answer 37

signals through GS3KB

Question 38

what is Lissenencephaly

Answer 38

disease that effects the gyrie formation of the brain
smooth brain

Question 39

what is the significance of the link of DISC-1 mutations and lissencephaly

Answer 39

puts DISC-1 as a risk factor for schizophrenia in a pathway that controls neural development

Question 40

what is neuregulin

Answer 40

a growth factor that interacts with receptors to regulate neuronal differentiation and migration

Question 41

why may neuregulin be a risk factor for schizophrenia

Answer 41

reducing the function of glutamate receptors - NMDA receptors that regulate mesocortical dopaminergic pathways