24 - Psychosis Flashcards
What is pyschosis?
Refers to mental disorders in which there is loss of contact with reality, affecting a persons ability to think, feel, and act
What is schizophrenia? What type of symptoms are there?
Severe psychotic disorder that is diagnosed if a person has 2 or more symptoms for 6 months
positive symptoms: mental phenomena that are absent in healthy individuals (eg hallucinations and delusions)
negative symptoms: loss or impairment of normal psychological function (eg loss of motivation and social withdrawal)
cognitive symptoms: poor concentration, disorganized thinking, poor memory
Sometimes similar classes of neurons are grouped together. What are the two classes talked about?
Catecholamines (dopamine, noradrenaline, and adrenaline)
Monoamines (dopamine, noradrenaline, serotonin)
What is the dopamine hypothesis?
symptoms of schizophrenia are due to the hyperactivity of the dopamine system
based on inferential evidence:
- drugs that increase synaptic dopamine can cause delusion and hallucinations at high doses
- drugs that block dopamine receptors are effective antipsychotics (first generation antipsychotics)
Where are dopamine neurons located?
midbrain (ventral tegmental area and substantial nigra)
mesocortical/mesolimbic system: dopamine neurons located in the VTA project to the striatum and the prefrontal cortex
these regions mediate memory, learning, affect and thought organization
hyperactivity in this pathway contribute to psychotic symptoms
Blocking dopamine transmission is effective at treating the (blank) symptoms of schizophrenia
positive
Describe dopamine receptors
G-protein coupled receptors. Two classes of dopamine receptors: D1 and D2
D1 receptors stimulate adenylate cyclase via Gs protein and subsequently active cAMP dependent protein kinases
D2 receptors are coupled to Gi and inhibit the activity of adenylate cyclase
What is the nigrostriatal system?
a dopamine pathway
dopamine neurons in the substantia nigra that project to the striatum
involved in movement initiation
inhibiting this pathway is involved in the production of extrapyramidal symptoms (movement disorders) including tardive dyskinesia (involuntary movements of the face and mouth) after long-term use of some antipsychotics
What is the tuberoinfundibular system?
Dopamine pathway. Dopamine neurons in the arcuate nucleus that control hormone release in the pituitary
dopamine released here inhibits the secretion of prolactin and growth hormone
long-term use of some anti-psychotics is associated with hyperprolactinemia (increased prolactin release)
associated with amenorrhea, decreased libido, and infertility
What is the glutamate hypothesis?
symptoms of schizophrenia linked to deficiencies in glutamate signaling, particularly in the cortex
Support comes from effects of PCP and ketamine which are NMDA antagonists that produce hallucinations and paranoid delusions
What is the current theory for schizophrenia relating to the glutamate hypothesis?
schizophrenia is associated with hypofunctional NMDA receptors on GABA interneurons in the cerebral cortex. This hypofunction leads to overactivation of downstream glutamate signaling to the VTA
What is the serotonin hypothesis?
Symptoms of schizophrenia due to increased serotonin signaling
LSD is agonist
Evidence: some 5HT agonists are hallucinogenic and 5HT antagonist improves positive symptoms of schizophrenia
What is the current theory based on the serotonin hypothesis?
activation of 5HT-2A receptors in the prefrontal cortex cause hallucinations by enhancing excitation of glutamate neurons (activating mesolimbic dopamine system)
5HT-2A antagonists block glutamate release in the cortex, thus reducing hallucinations and other positive symtoms
What are the 2 major groups of antipsychotic drugs?
1st generation antipsychotics/typical antipsychotics
2nd generation antipsychotics, or atypical antipsychotics
What are typical antipsychotics
targets both classes of dopamine receptors (d1 and d2) but efficacy particularly relates to d2 receptor antagonism
haloperidol (fast on and slow off), chlorpromazine (fast on fast off)
fast on = high extrapyramidal
slow off = too much prolactin
slow on fast off
What are atypical antipsychotics?
most are antagonists at both 5HT receptors and D2 receptors because they bind looser (lower affinity) to dopamine receptors than first generation antipsychotics they produce less dopamine related side effects
clozapine, risperidone
slow on fast off
At what occupation % do D2 receptors cause side effects?
80%. Parkinson-like side effects (extra pyramidal symptoms, including tardive dyskinesia (involuntary movements of the face and jaw), elevated prolactin (hyperprolactinemia))
In the mesolimbic, mesocortical, and nigrostriatal pathway, where is dopamine released?
synaptic cleft
In the tuberoinfundibular pathway. where is dopamine secreted into?
blood stream
What is agranulocytosis?
Loss of white blood cells. Clozapine has unique affinity for dopamine D4 receptors and causes serious side effects
