Psychosis Flashcards
What is psychosis?
Illness characterised by loss of boundaries with reality and loss of insight, with primary features of delusions, negative symptoms and cognitive disorder
1 week duration at significant severity = psychotic episode
Delusion:
Belief that is fixed, false and not keeping with socio-cultural milieu
held firmly, not affected by evidence to the contrary
Conceptual Disorganisation:
thought processes are confused and disconnected as demonstrated by what they say
observed (not complained of by patient)
aka loosing of associations of thought
Hallucination:
perception experienced in the absence of an external stimulus
in any sensory modality but most common is auditory
due to internal pereception attribution error
What are the three categories of symptoms of psychosis?
- positive symptoms (gain)
- negative symptoms (loss)
- cognitive symptoms
Psychosis Symptoms:
Auditory Hallucinations in Schizophrenia:
- 60-70% of patients
- usually, derogatory voices
- 25% patients made a suicide attempt
in response to these voices - refractory to treatment in 25-30%
patients
Neural Activity during auditory hallucinations shows
speech generation areas active likely misperception of inner thought
left superior temporal gyrus
failure to attenuate somatosensory cortex during self speech; hence perceived as other speech
White Matter Connections:
superior longitudinal fasciculus connects speech areas to temporal auditory perception areas
connects brocas and wernickers
broca = generation
Risk factors for Psychosis:
- obstetric complication
- childhood trauma
- immigration status
- cannabis use
- male gender
genetic risk of schizophrenia
Risk factors for schizophrenia are bot
environmental and genetic and same as psychosis
Why does schizophrenia present between late teens and early twenties?
- deficient myelination
- reduced interneuron activity
- excessive excitatory pruning
more inhibitory synapses and less excitatory synapses at this developmental stage
Trajectory of Psychosis: Stages:
How many dopaminergic pathways are ther in the brain?
4
Dopaminergic Pathways:
Dopaminergic Pathways: Mesolimbic:
- function (2)
- function 1 relation to
psychosis/symptoms - function 2 relation to psychosis
- regulates the limbic system, which is
involved in reward processing
(pleasure) and salience (threat
evaluation) - psychosis = dysfunction of the salient
part of the mesolimbic pathway;
generally hyperactive mesolimbic
pathways hence delusions - drugs of abuse target the reward
processing pathway, creating feelings
of pleasure - chronic drug use can lead to the
dysregulation of the salient part,
causing drug-induced psychosis
Which dopamine receptor is most linked to psychosis?
D2
Which dopaminergic system is depicted below?
The Mesolimbic system
Dopaminergic Pathway: Mesocortical System:
- function
- psychosis
- symptoms
- regulates the prefrontal cortex, which
is involved in: cognition, motivation,
social engagement - psychosis = dysfunction of
mesocortical system = hypoactive - results in reduced stimulation of the
prefrontal cortex causing the negative
symptoms of psychosis (cognitive
impairment and social withdrawal)
Which dopaminergic pathway is depicted below?
Mesocortical System
Dopaminergic Pathway: Nigrostriatal System:
*not involved in developing symptoms
of schizophrenia but are targeted by
antipsychotics
- regulates the basal ganglia, which is
involved in movement and initiation of
movement - antipsychotics can interfere causing
impaired movement ->parkinsonian symptoms (ridgidity, akinesia, tremor)
Which dopaminergic pathway is depicted below?
Nigrostriatal System
Dopaminergic Pathway: Tuberoinfundibular Syystem:
*not involved in developing symptoms
of schizophrenia but are targeted by
antipsychotics
- regulates HPA, which is involved in
control of endocrine system; sex and
growth hormones - antipsychotics can interfere causing
hormonal problems
Which dopaminergic pathway is depicted below?
Tuberoinfundibular System
Antipsychotics:
- mechanism of action
- effects
- effect
- post-synaptic dopamine antagonists
- all antipsychotics modulate the
dopaminergic system - to have an effect must block 60-70% of
dopamine receptors
Effects of antipsychotic drugs on the mesolimbic system:
- suppress both pleasure (reward
processing) and threat evaluation
side effect = dysphoria (loss of pleasure
in life)
hence patients may not comply
Effects of antipsychotic drugs on the mesocortical system:
- suppresses the mesocortical system
further - worsens negative symptoms (social
withdrawal etc) - good for positive symptoms which are
from mesolimbic dysfunction
Newer atypical antipsychotics target
suppression of mesolimbic, whilst stimulating mesocortical
Differences between first and second generation antipsychotic side effects:
- second gen do not cause movement
and hormonal problems - second gen cause cardio-metabolic
symptoms like early onset diabetes
and CVDtypical = dopamine antagonist
2nd gen/atypical = dopamine and serotonin antagonist
3rd gen/atypical = partial dopamine antagonist (aripiprazole)
Why do second generation antipsychotics cause less side effects?
- more dynamic with ‘off-time’
- doesn’t block the postsynaptic
dopaminergic receptors for as long - blocks 5HT receptors (sertonergic)
which slows the release of dopamine
Core Drug: Clozapine:
- type of antipsychotic
- used for
- why
- atypical
- reserved for treatment-resistant
illness (two other drugs must fail) - side effects: sedation, toxic effect of
low white cell counts hence requires
intensive blood monitoringneutropenia (low neutrophils), constipation
Long-term Effects of Antipsychotics:
- sensitisation
- if dopamine receptors keep being
blocked, sometimes cells respond by
increasing the number of receptors - bigger response from endogenous
dopamine if medication is stopped
Antipsychotic Drugs: Side Effects:
**- anticholinergic = dry mouth, dilated
pupils
- antiadrenergic
- antihistaminergic **
Blocking nigrostraiatal pathway:
** - acute dystonia = sharps muscle
spasms in face and neck
- akathisia: sense of inner
restlessness
- parkinsonism
- tardive dyskinesia: long term
abnormal movements of mouth and
lips**
Impact on hypothalamus affecting satiety hence patients commonly overeat hence prone to develop type II diabetes and causes CVD
direct impact on functioning of the heart -> contractility
lengthens QTc interval -> cardiac arrest
hence ECG monitoring before and during drug usage
Non-Pharmalogical Treatments for Psychosis:
- CBT: reduce distress related to
symptoms, reduce intensity of
abnormal beliefs by understanding the
links between thoughts, feelings and
actions - art therapies -> learn to relate to other
ppl - family intervention -> manage home
life
Glutametergic Theory of Schizophrenia:
ketamine as an NMDA receptor antagonist to cause schizophrenia like system
affects inhibitory neurons, disinhibtiion of glutamate
increases excitatory activity in the prefrontal cortex
