Psychotic Flashcards
What are the 2 main types of symptoms in psychosis?
- positive symptoms:
Reflect an ecess of normal function ( e.g, Delusions, hallucinations, distortions or exaggerations in language and communication, disorganized speech, disorganized behaviour, catatonic behaviour, agitation) - negative symptoms: lack of normal functioning (5 A’s: Alogia, Affective blunting, asociality, anhedonia, avolitions)
What is alogia
unable to produce normal speech
avolitions
lack of goal directed beahviour
the schizephrenia medications available are more benficial for which types of symptoms?
effective for positive symptoms, less effective for negative
What are some additional symptoms in schizophrenia (other tha positive and negative)
- Cognitive symptoms
- Aggressive symptoms
- Affective symptoms
Which brain circuits are hypothesized to be related to positive symptoms?
mesolimbic circuits
Which brain circuits are hypothesized to be related to negative symptoms?
mesocortical/prefrontal cortex
nucleus accumbens reward cicuits
Which brain circuits are hypothesized to be related to affective symptoms?
ventromedial prefrontal cortex
Which brain circuits are hypothesized to be related to aggressive symptoms?
orbitofrontal cortex and amygdala
Which brain circuits are hypothesized to be related to cognitive symptoms?
dorsolateral prefontal cortex
What is the stress diathesis model of schizophrenia?
gene x environment interaction:
- genetic vulnerability
- stress from the environment combined with this vulnerability leads to symptoms
What is the Dopamine hypothesis of schizophrenia ?
evidence?
Abnormal levels of DA in different areas of the brain drive symptoms
There is too much dopamine in SOME neurocircuits (particularly mesolimbic) which results in psychosis and positive symptoms
- Drugs that increase DA in those ciruits can cause positive symptoms (e.g., delusions, hallucinations)
- Drugs that decrease DA reduce positive symptoms
There is a lack of DA in OTHER neurocircuits that cause frontal lobe hypoactivity
- results in poor attention and concentration, executive control etc.
Low DA results in negative symptoms
What are the different types of dopamine receptors?
Which type is hypothesized to be related to schizephrenia?
D1-5
D2 (blocking D2 reduces positive symptoms)
also role of D1 and D3
Which pathway is really important in movement?
substantia nigra to striatum
What are other hypothesizes causes of schizophrenia?
Glutamate may control DA activity
Abnormal glutamate activity therefore may cause problem in DA functioning and psychosis
Could explain the high vs low DA in different circuits
Describe the glutamate-glutamine cycle
EAATs brings glutamate into glial cell
- Glutamine synthetase converts glutamate to glutamine
- Glutamine is transported from the glial cell into the presynaptic neuron
- glutamine is converted into glutamate and packaged into
Vesicular glutamate transporters (VGLUT) - releases into synapse
- Terminated by excitatory amino acid transporters (EAATs) in to glial cells
starts over
What are the subtypes of glutamate
where can they all be located?
NMDA (ion gated)
AMPA/kainate (ion gated)
mGluR (metabotropic)
All be located on post synaptic neuron
Which type of glutamate receptors are responsible for the most rapid Excitatory postsynaptic potentials?
AMPA/kainate receptors
What makes NMDA receptors unique?
even though they are ionotropic, it allows the entry of calcium (as well as sodium or potassium)
-> calcium can act as a second messenger
In order to fire:
in addition to glutamate
require the presence of of a co-transmitter (serine or glycine)
must also have SOME level of depolarization
Too much glutamate in brain can lead to?
neurotoxicity/cell death
NMDA Receptor Insufficiency Theory of Schizophrenia
Glutamate NMDA receptors are located on the post synaptic neuron of GABAneric Neurons (release GABA)
- these receptors are defective
- causes GABA neurons to lose tone/activity (not doing their inhibitory job)
- results in excessive glutamate activity
- this excessive glutamate results in exesssive DA activity in the mesolimbic system
- DA activity results in psychosis
in mesocortical system there isa different configuration (there is an additional interneuron) which results in inaquequate DA in the mesocortical
Drugs that are good at controlling positive symptoms do what?
Antagonist to D2 receptor (block D2 receptors)
What happens if you agonize 5- HT2A receptors?
psychedelic effect
Extrapyramidal Symptoms (EPS) caused by conventional antipsychotics
related to blockage of DA in nigrostriatal pathway
Movement issues
– Dystonia: muscle spasms/cramping, esp. neck/shoulders
– Akathesia: restless agitation
– Parkinsonian symptoms: jerky movements,
shuffling
– Tardive dyskinesia: involuntary facial movements (develops later – months to years)
What are other negative side effects of conventional antipsychotics? (in addition to EPS)
- Hyperprolactinemia
- Metabolic syndrome
- QTc interval prolongation
What do Atypical or Second Generation Antipsychotics do?
anticholinergic
- Greater affinity for 5HT in general, and 5- HT2A specifically (acts as an antagonist)
- Blocking cortical 5-HT2A receptors increases dopamine release
- Greater anticholinergic action coupled with transient D2 action may have the best support to explain improved EPS
