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Neuropharmacology of CNS disorders > Schizophrenia > Flashcards

Schizophrenia Flashcards

1
Q

what is the number one cause of premature death among people with schizphrenia?

A

suicide

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2
Q

what are some positive symptoms of schizophrenia?

A
  • hallucinations
  • thought disorders (incoherent speech, delusions)
  • sterotypes behaviours (repeptitive movements)
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3
Q

what are the negative symptoms of schizophrenia?

A
  • poverty of affect (depression, low mood)
  • cognitive impairment
  • temporal disorientation
  • social withdrawal
  • inability to feel pleasure or act spontaneously
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4
Q

what is the time course of schizophrenia?

A

positive -> negative symptoms
onset 15-25 years old

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5
Q

out of first degree relatives who has the highest rates of schizophrenia among relatives

A

identical twins
children - both parents schizophrenic

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6
Q

what the proposed causes of schizophrenia?

A
  • Genetic
  • psychoscial
  • structural brain damage
  • viral infection
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7
Q

give 4 potential causes of schizophrenia

A
  • Genetic
  • Psychosocial
  • Structural brain damage
  • Viral infection
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8
Q

what evidence from adoptive studies was there for a gentic cause of schizophrenia?

A

Tienari looked at this, babies adopted away from ‘normal’ or ‘schizophrenic’ mothers:
incidence of schizophrenia among babies from noraml birth mothers was 1%
incidence of schizophrenia among babies from schizophrenic birth mothers was 8%

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9
Q

what is the concordance rate of schizophrenia among monozygotic twins?

A

48%

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10
Q

what are endophenotypes?

A
  • A trait related to the psychiatric disorders and its genetic basis
  • things you can recapitulate in animal models to measure/study psychiatric disorders
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11
Q

give an example of an endophenotype for schizophrenia

A
  • A good example is pre-pulse inhibition
    o Essentially this is a measure of an individuals startle response
    (eg by an unexpected noise stimulus, then measure ocular motor response. In a normal individual the second response will be lower than the first response, this is called sensory motor gating.
    pre pulse inhibition is typically impaired in schizophrenia (some sort of aberration in sensory motor gating)
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12
Q

what evidence is there that there is a psychosocial cause for schizophrenia

A
  • adolescent onset – at a time where there are a lot of changes and stress
  • stress can precipitate illness - the first instance of illness and subsequent episodes seem to follow stress in life
  • higher rate of relapse in ‘emotionally charged’ home environment
  • blunted cortisol response
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13
Q

give evidence that structural brain damage could be a cause of schizophrenia

A

in schizophrenics there has been observed:

some studies (CAT Scans and MRI) show ventricular enlargement and
decreased volume of temporal lobe (hippocampus)
cytoarchitectural abnoramlities in cortex

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14
Q

cytoarchitectural abnormalisties in the cortex of schizophrenics manifests as:

A
  • decreased numbers of small neurones in superficial layers
  • increased numbers of large neurones in deeper layers
  • Loss of volume – not neurons
  • Reduction in dendritic spine density
    o In schizophrenia aberrant spine density has been reported in multiple brain regions – reduction in volume of grey matter in the cortex
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15
Q

what cricumstantial evidence pointed to viral infection as a potential cause of schizophrenia?

A

higher incidence in patients born in late winter or spring
hypothesis that exposure of mother to virus during second trimester increases risk of schizophrenia to the child

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16
Q

what are the major sites of brain dysfunction in schizophrenia?

A
  • Limbic structures in the temporal lobes (decreased size)
  • dysfunction of dominant cerebral hemisphere
  • hypofunctionality of dorsal-lateral pre-frontal cortex
  • basal ganglia (change in size of nuclei)
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17
Q

give evidence to support limbic structures as the site of brain dysfunction in schizophrenia

A

Some limbic structure harboured in the temporal lobe
Decreased size of temporal lobe, (due to dendritic pruning not death of neurons)
Increase activity during auditory hallucination
- Temporal lobe involved in language and auditory processing and emotion and memory

in indivudials with epilepsy, if the locus for the seizure is in the temporal lobe then they will experience hallucinations during the seizures.
Those with tumour in the temporal lobe also experience hallucinations that can be psychotic

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18
Q

give evidence to show dysfucntion of dominant cerebral hemisphere in schizophrenics is the site of brain dysfunction

A

Lateralisation of cerebral function is important for normal cognitive processing
Left hemisphere is specialised for verbal function (in most indixisualts) and the right hemisphere is for special processing)
The corpus callosum that allows the hemispheres to communicate means we don’t notice this
In normal individuals this is shown by increased brain activity to the left side of the brain during a verbal task
This lateralisation appears disrupted in schizophrenia
Don’t show the same lateralisation of function, this might underpin the poor performance in some cognitive tasks

More recent studies focussing on cennectivity - via mapping tracts using diffusion tensor imaging
Anatomical abnormality in the commissural trascks in indivuduals with psychosis – maybe this is the anatomical pehnoemenon that’s resulting in disrupted lateralisation

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19
Q

give evidence that the hypofunctionality of dorsal lateral pre frontal cortex is the site of brain dysfunction in schizophrenics

A

using the wisconsin card sorting test to assess decision making capability, metabolic activity was measured in the brain of control vs schizophrenic subjects

schizophrenic performed poorly in the task - and the metabolic activity in the dorsal lateral pre frontal cortex was much lower than in the control subjects

studies mapping changes in cortical thickness showed that schizophrenics had thinning of the cortex

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20
Q

give evidence that the basal ganglia is the site of brain dysfunction in schizophrenia

A

(site of action of antipsychotics)
Involved in sensory motor gating
A number of studies reported changes in sizes of nuclei in the basal ganglia occur in schizophrenia relative to the control – resulting in changes in sensory motor processing

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21
Q

what area of the brain is involved in the postive symptoms of schizophrenia

A

temporal lobe

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22
Q

what area of the brain is involved with the negative symptoms of schizophrenia?

A

prefrontal cortex

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23
Q

give 4 pieces of indirect, circumstantial evidence to implicate dopamine in the neurchemical basis of schizophrenia

A
  1. Reserpine is an antipsychotic – has sedative, calming properties, obtained from indiand herbal snake root. Acts to deplete levels of dopamine in the brain
  2. Amphetamine causes toxic psychosis in susceptible individuals – elevates dopaminergic levels in the brain, clinicians say this psychosis is indistinguishable from schizophrenia itself. Responds to antipsychotic drugs, phenotypically similar to schizophrenia
  3. L-DOPA can trigger psychotic episodes – parkinsons treatment, those receiving it sometimes experience psychotic episodes as a side effect,
  4. Chlorpromazine – the first antipsychotic, works by increasing dopamine turnover
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24
Q

how were chlorpromazine antipsychotic properties discovered?

A

Discovered by chance (serendipity)

Discovered in the 1940s by a French military surgeon.
Testing derivates of promethysine (an antihistamine) to find beneficial properties in calming agitated patients.

Chlorpromazine properties helps agitated patients
Calmed them but was not a sedative – first use

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25
Q

when did chlorpromazine enter common psychiatric use and why was it revolutionary?

A

Entered common psychiatric use in 1950s – revolutionised psychiatric medicine. Previously the only way to manage psychotic patients was put into a straight jacket. Now they could give the drug, even though its effect were quite significant

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26
Q

give two alternative names to chlorpromazine

A

First trade name Largactil
Thorazine

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27
Q

how does chlorpromazine work?

A

chlorpromazine blocks the dopamine receptor
> less inhibition of dopamine release, leading to increase release of dopamine, this lead to increase of dopamine metabolites in the CSF

  • this suggest chlorpromazine is a DA receptor antagonist
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28
Q

how is catelepsy used as a screen for schizophrenia?

A

Catalepsy is a state of immobility – you can induce it ina mouse by giving dopamine receptor antagonist (by blocking signalling in the nigrostriatal pathway, extrapyramidal motor control)
Chosen by pharma because it is a very simple assay
Take mouse put on a grid, mouse will hold on, increase angle of grid, untreated mouse will be able to hang on . if injected with a drug that induces catalepsy, mouse wont be able to hold on
Another is, put mouse on rotating rod, most mice can hold on, but if it has catalepsy it won’t be able to hold on as long

Drawbacks: not entirely selevtive for dopamine receptor antagonists – opiates also cause catalepsy. Built into the screen is the discovery of a drug that has motor side effects

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29
Q

describe the experiment that investigated whether dopamine receptor blockage explain the antipsychotic action of chlorpromazine

A

The affinity of various antipsychotics to D2 at their clinical dose is tested
The clinical antipsychotic doses correlate with the antipsychotic dissociation constant

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30
Q

what inconsistancies are there about the dopamine hypothesis of schizophrenia

A
  • no consistent evidence for increase in dopamine levels, or release or metabolites
  • measurements made in post mortem brain show an increase in D2 receptors- however, this could be due to drug treatment
  • measurements in drug naive patients using PET do not show consistent increased levels of D2
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31
Q

schizophrenia was first accurately described by __ in __

A

Swiss psychiatrist Bleuler 1908

“fragmentation of cognitive processes and personality”

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32
Q
A
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33
Q

what is paranoid schizophrenia?

A

This is the most common type of schizophrenia. It may develop later in life than other forms. Symptoms include hallucinations and/or delusions, but your speech and emotions may not be affected.

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34
Q

what is hebephrenic schizophrenia?

A

Also known as ‘disorganised schizophrenia’, this type of schizophrenia typically develops when you’re 15-25 years old. Symptoms include disorganised behaviours and thoughts, alongside short-lasting delusions and hallucinations. You may have disorganised speech patterns and others may find it difficult to understand you.
People living with disorganised schizophrenia often show little or no emotions in their facial expressions, voice tone, or mannerisms.

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35
Q

what is catatonic schizphrenia?

A

This is the rarest schizophrenia diagnosis, characterised by unusual, limited and sudden movements. You may often switch between being very active or very still. You may not talk much, and you may mimic other’s speech and movement

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36
Q

what is undifferentiated schizophrenia?

A

Your diagnosis may have some signs of paranoid, hebephrenic or catatonic schizophrenia, but it doesn’t obviously fit into one of these types alone.

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37
Q
A
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37
Q

what is residual schizophrenia?

A

You may be diagnosed with residual schizophrenia if you have a history of psychosis, but only experience the negative symptoms (such as slow movement, poor memory, lack of concentration and poor hygiene).

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38
Q

what is simple schizophrenia?

A

Simple schizophrenia is rarely diagnosed in the UK. Negative symptoms (such as slow movement, poor memory, lack of concentration and poor hygiene) are most prominent early and worsen, while positive symptoms (such as hallucinations, delusions, disorganised thinking) are rarely experienced.

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39
Q

what is cenesthopathic schizophrenia?

A

People with cenesthopathic schizophrenia experience unusual bodily sensations.

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40
Q

what is unspecified schizophrenia?

A

Symptoms meet the general conditions for a diagnosis but do not fit into any of the above categories

41
Q

give 8 types of schizophrenia

A
  • paranoid
  • hebephrenic
  • catatonic
  • undifferentiated
  • residual
  • simple
  • cenesthopathic
  • unspecified
42
Q

which relatives have the highest rates of schizophrenia (of schizophrenic parents)?

A

identical twins and
children - both parent schizophrenic

43
Q

how was a blunted cortisol response measured in schizophrenics?

A

Measure salivary cortisol in normal vs schizophrenic patients you see much lower cortisol levels – in schizophrenia there is a blunted response to stressors. Abnormal response to stress, maladaptted

44
Q
A
45
Q
A
46
Q

What is the dopamine hypothesis?

A

The symptoms of schizophrenia are due to excess dopamine neurotransmission in mesolimbic and mesocortical regions of the brain

47
Q
A
48
Q

using a selective ligand for D1 receptors, PET studies revealed what in schizophrenics

A

‘decrease prefrontal dopamine D1 receptors in schizophrenia revealed by PET’

Dopamine receptor signalling in the prefrontal cortex is thought to be important in memory and cognitive importance

49
Q

what were the observations when rats were chronically administered antipsychotics for weeks and activity of dopaminergic neurons measured?

A
  1. Before any antipsychotic: activity og the VTA neurones greater than that of SN (mesocortical neurosn had a higher level of activity)
  2. Acute antipsychotic treatment; increase activity of the mesolimbic VTA neurons BUT no change in activity of the mesocortical dopamine neurones
  3. Chronic (3 weeks) antipsychotic treatment; mesolimbic VTA neurons becomes silent (stop firing)
    BUT non change in activity of the mesocortical neurons

Diff regions of the brain with dopamine receptors are showing different responses – a time dependent responses as well – so the lag in the time course of the therapeutic benefit may match this observation

50
Q

what is the baseline activity of dopamine release from mesolimbic and mesocortical neurons

A

dopamine release from mesolimbic is lower than that from the mesocortical neurons

51
Q

what happenes to the dopamine activity in mesolimbic/mesostriatal areas after chlorpromazine is added and why ?

A

chlorpromazine blocks presynaptic autoreceptors, blocking the feedback inhibition of dopamine -
initial increase in activity of neurons and release of dopamine
(chlorpromazine is a competitive antagonist, it doesnt cause a functional block because of the increase in dopamine (agonist))
over time the increased neuronal activity makes it entera state of deopolarising block - prolonged depolarisation inactivates voltage gated sodium channels meaning it cannot fire (this is the basis for the silence of the neuron following chronic treatment)

52
Q

why dopamine release different between mesocortical and mesolimbic dopaminergic neurons after chlorpromazine?

A

evidence for autoreceptor on the mesolimbic receptors – however the mesocortical neurons don’t seem to express autoreceptors

chlorpromazine doesnt distinguish between pre and post synaptic receptors
in mesolimbic neurons
chlorpromazine blocks presynaptic autoreceptors of mesolimbic neurons, blocking feedback inhibition, initially increasing dopamine release however dopamine overcomes the synaptic block. the increase neuronal activity makes the cell enter a state of depolarising block meaning it cant fire

in mesocortical neurons, no autoreceptos so the net effect is overall change in balance of signalling in DA pathways; relative increase in dopamine release in mesocortical neurons

53
Q

what causes the lag in clinical benefit after antipsychotics?

A

depolarising block

54
Q

list 3 typical antipsychotics

A

Phenothiazines (chlorpromazine)
Thioxanthenes (flupenthixol)
butyrophenones (haloperidol)

55
Q

what are the two major limitations of typical antipsychotics?

A

not effective in all patients (refractory to treatment)
only effective against positive symptoms

56
Q

what are the side effects of typical antipsychotics?

A
  • Weight gain
  • Sedation
  • Postural hypotension
  • Atropine-like- side effects (block muscarinic receptors)
  • Hyperprolactinaemia (can cause breast development & lactation)
  • Neuroleptic malignant syndrome (very rare but life threatening) (if not addressed within 72 hours then can be very dangerous, requires treatment withdrawal, characterised by rigidity, high fever, confusion, susceptibility and cause not clear)
  • Movement disorders (very common and destressing)
    o Acute eg Parkinson like syndrome
    o Chronic eg Tardive dyskinesia
57
Q

why do typical antipsychotics cause movement disorders?

A

because they block dopamine receptors in the nigrostriatal pathway

(very common and limiting distressing, lead to non compliance with the medication)

58
Q

what is tardive dyskinesia?

A

a neurological disorder characterized by involuntary movements of the face and jaw.

Irreversible

(Repetitive, purposeless movement, often of the mouse, lips and tongue)

59
Q

what are the three hypothesis for antipsychotic induced tardive dyskinesia?

A
  • Dopamine receptor supersensitivity hypothesis
  • Neuroleptic toxicity hypothesis
  • GABA hypothesis
60
Q

atypical antipsychotics are reportedly more effective against what symptoms of schizophrenia

A

REPORTEDLY more effective against negative symptoms

61
Q

what are the side effects of atypical antipsychotics?

A

excessive weight gain, diabetes mellitus, QTc prolongation, extrapyramidal side effects, myocarditis, agranulocytosis, cataracts, and sexual side effects,

62
Q

why is clozapine classed as an atypical antipsychotic?

A

it induces less sedation

63
Q

what happened when clozapine was first introduced into the clinic?

A

– when introduced it was very successful, induced less sedation (alerting propoerties effective against negative symptoms), worked against refractive patients, reportedly lower incidence of tardive dyskinesia.
HOWEVER some patients died of fatal form of anaemia agranulocytosis

64
Q

why does haloperidol have side effects of hyperprolactinaemia and tardive dyskinesia?

A

at the therapeutic dose, it will block D2 and D3 specifically

65
Q

how does the receptor profile of clozapine differ from the receptor profile of haloperidol?

A

at the therapeutic dose Haloperidol will block D2 and D3 specifically

at the therapeutic dose clozapine will effectively block D4 (not other dopamine receptors), it will also block muscarinic and 5HT receptors

66
Q

what receptors does clozapine effectively bind at therapeutic dose?

A

D4
5HT2, 3, 6, 7
alpha 1
M1

67
Q

how does the receptor profile of cloazpine explain the associated effects?

A

Only effectively blocking the D4 receptor at therapeutic concentration - These receptors are mainly expressed in the limbic areas of the brain. involved in mood and behaviour, where dopaminergic dysfunction may underpin the positive symptoms of schizophrenia

Blocks muscarinic receptors – explanation for low incidence of extrapyramidal symptoms.
Does not block D2 receptors – D2 in basal ganaglia highly implicated in the extrapyramidal

Blocks 5HT2 receptors - may prevent the Parkinson-like motor side effects of antipsychotics

68
Q

give 3 proteins implicated in the genetic suseptibility to schizophrenia

A

DISC-1
NEUREGULIN
CATECHOL-O-METHYL-TRANSFERASE

69
Q

insight into the genetic basis of schizophrenia is provided by…

A

 association with chromosomal microdeletion syndrome
 rare familial variants of schizophrenia

70
Q

what is Velocardio facial syndrome (VCFS)?

A

one of the most common multiple anomaly syndromes in humans.
a genetic condition characterized by abnormal pharyngeal arch development that results in defective development of the parathyroid glands, thymus, and the conotruncal region of the heart
Deletion of 1.4 to 3Mb in chromosome 22 (includes ~30 genes)
Typically a spontaneous deletion

71
Q

how is Velocardio facial syndrome elated to schizophrenia?

A

Increased incidence of psychiatric disorders, including schizophrenia
Higher incidence of deletion in chr 22 in schizophrenic population (VCFS is caused by deletion of bases in chr22)

72
Q

what is catechol-O-methyl-transferase (COMT)

A

metabolic enzyme for catechols (ie dopamine)
highly expressed in prefrontal cortex

73
Q

what residue variantion results in two COMT alleles in humans

A

valine 108
methionine 108- less stable enzyme

74
Q

how is COMT implicated as a risk factor in schizophrenia?

A

two COMT alleles in humans
valine 108
methionine 108- less stable enzyme
hypothesis that met-108 gives rise to higher synaptic dopamine
but val108 is the allele that shows linkage with schizophrenia and impaired cognitive function
ties in with idea that dopamine in prefrontal cortex is involved in working memory so lower levels of signalling may cause cognitive impairment (COMT enzyme is more stable so metabolises dopamine better)
increased function of COMT is a risk factor

75
Q

How was DISC1 identified?

A

Scottish family with inherited psychiatric disorders
Three children each have diagnosis of mental illness
Using cytogenetics they found in these indivisuals DISC1
Disrupted in schizophrenia – DISC-1
Is highly penetrant – those that carry a mutation 50 % had a psychiatric condition – not complete penetrance
The genetic mutation involves a chromosomal translocation
Chromosomal translocation can introduces DNA breaks
This is where the mutation is introduced

76
Q

when does DISC1 have increased expression?

A

during neuronal development

77
Q

what neurons is DISC1 expressed in ?

A

cortical neurons

78
Q

what proteins does DISC1 interact with ?

A
  • GSK3beta
  • GSK3beta(DIXDC1)
  • NDEL1(DIXDC1)
  • LIS1
  • BBS (PCM1)
  • Girdin KIAA1212
  • PDE4
  • KAL7(PSD-95)
  • TNIK
    *
79
Q

DISC1 is involved in what neuronal processes

A

Neuronal proliferation
Neuronal migration
Key signalling pathway
Spine regulation
Synapse maintainence

80
Q

what protein does DISC1 signal to to control neural proliferation ?

A

GSK3beta

81
Q

what is Lissencephaly?

A

a rare, gene-linked brain malformation characterized by the absence of convolutions (folds) in the cerebral cortex and an extremely small head (microcephaly)
- Mutations in Lis1 cause lissencephaly
- Associated with severe learning difficulties
- Neural development affected – gyri (folds) don’t develop properly

  • Lis1 is an interacting partner with DISC 1
  • Link between DISC1 and mutations that cause Lissencephaly (smoothbrain)
82
Q

Linkage analysis and fine genetic mapping identified a locus on chromosome 8 as a risk factor for schizophrenia - this region encodes what protein?

A

neuregulin

83
Q

what is neuregulin?

A

a growth factor that interacts with ErbB receptors that regulates neuronal differentiation and migration

84
Q

how is neuregulin implicated in schizophrenia?

A

Post mortem analysis of brain from schizophrenics has identified an increase in levels of mRNA for neuregulin
Current hypothesis is that an increase in neuregulin signalling is a risk factor for schizophrenia (possibly by reducing the function of the glutamate receptor, the NMDA receptor)
Risk factor because neuregulin is reducing function of NMDA receptor giving rise to increase in dopaminergic activity.

85
Q

what evidence is there of prefrontal cortex and subcortical dopamine in the negative and positive symptoms of schizophrenia?

A
  1. hypofunctionality in brain imaging
  2. altered cytoarchitecture in PM brain
  3. decreased D1 in PM brain
  4. lesions in primates give negative symptoms
  5. DISC1 and COMT highly expressed in cortex
  6. DISC1 implicated in neuronal migration and interacts with proteins which are mutated in lissencephaly indicates that there may be neurodevelopmental defect that causes abnormality in organisation of cortical neurones
86
Q

what causes the positive symptoms of schizophrenia?

A

loss of control of subcortical systems (causing hyperfunctionality)

(cortex hypofunctionality leads to a loss of inhibition of the subcortical systems)

87
Q

what causes the negative symptoms of schizophrenia?

A

hypofunctionality of the cortex

88
Q

describe the projections of the mesolimbic and mesocortical pathways

A

from the ventral tegmental area
to limbic structures (ventral striatum (including nucleus accumbens (NAcc) and olfactory tubercle), hippocampus, amygdala)
to the cerebral cortex (frontal cingulate,orbitofrontal cortex, prefrontal cortex and entorhinal cortex)
respectively

89
Q

what are the roels of the mesolimbic and mesocortical pathways?

A

cognitive functions, reward and motivation

90
Q

how do the prolactin levels confirm that the delay in therapeutic efficacy isnt due to the lack of effective d2 blockage

A

dopamine release from neurons in the arcuate nucleus of the hypothalamus travel in blood inhibiting release of prolactin from lactotroph cells in the anterior pituitary
antipsychotics block these D2 receptors (on the lactotrophs) leading to an elevation of prolactin which can be measured
elevated prolactin shortly after antipsychotic adminstration indicates that the d2 receptors are being effectively blocked therefore the delay in therapeutic efficacy is due to another reason

91
Q

what is depolarising block

A

prolonged depolarisation inactivates voltage gated sodium ion channels meaning the neuron cannot fire

92
Q

what are the side effects of typical antipsychotics caused by antihistamine receptor interactions

A

weight gain and sedation

93
Q

what are the side effects of typical antipsychotics caused by alpha adrenoreceptor interactions

A

postural hypotension

94
Q

what are the side effects of typical antipsychotics caused by dopamine (D2) receptor interactions

A

hyperprolactinaemia and movement disorders

95
Q

describe the basis of the dopamine receptor supersentitivty hypothesis behind antipsychotic induced tardive dyskinesia

A

when a drug blcos D2 receptors it will trigger plasticity in the circuit that leads to upregulation of dopamine receptors to compensate.
Elevation of D2 receptors in the nigrostriatal pathways therefore give rise to the dyskinesias

96
Q

describe the basis of the neuroleptic toxicity hypothesis of antipsychotic induced tardive dyskinesia

A

some studies using CAt?MRI show ventricular enlargement associated with long term antipsychotic treatment (this may be progression of the disorder but is unknown)

97
Q

describe the basis of the GABA hypothesis of antipsychotic induced tardive dyskinesia

A

long term studies on monkeys shows that those treated showed decrease in levels of enzyme, glutamic acid decarboxylase (GAD)(synthetic enzyme for GABA). this is taken as an indication of reduction in signalling of GABA neuronS in the basal ganglia.
Loss of GABA neurons in moneys treated with antipsychotics

altered gaba signalling is implicated in dyskinesic disease, huntingtons

98
Q
A
99
Q

how did the results form PET scans show that delayed therapeutic efficacy wasnt because of dysfunctional blockage of D2 receptors

A

Schizophrenia patients administered radiolabelled drug that binds D2 receptors, and do PET imaging
shows that within a short period of time after antipsychotics administration you have >80% occupancy of D2 receptors in the brain - this is a functional blockage therefore something else is responsible for the delay in therapeutic efficacy

Neuropharmacology of CNS disorders (8 decks)

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