Lecture 24 - Psychosis Flashcards
describe a range of mental disorders that involve symptoms of psychosis
psychotic disorders
refers to mental disorders in which there is a loss of contact with reality, affecting a person’s ability to think, feel, and act
psychosis
a severe psychotic disorder that is diagnosed if a person has two or more symptoms for six months
schizophernia
what are the positive symptoms of schizophrenia?
mental phenomena that are absent in healthy individuals (ie: hallucinations and delusions)
what are the negative symptoms of schizophrenia?
loss or impairment of normal psychological function (ie: loss of motivation and social withdrawal)
what are the cognitive symptoms of schizophrenia?
poor concentration, disorganized thinking, poor memory, etc
the risk of developing schizophrenia is highly influenced by:
genes
when does schizophrenia most often manifest?
early adulthood
one common theory is that schizophrenia is a:
biochemical brain disease
true or false: generally, neurons predominantely release one neurotransmitter
true
what is the dopamine hypothesis?
the symptoms of schizophrenia are due to the hyperactivity of the dopamine system
what are the two major pieces of evidence for the dopamine hypothesis?
- drugs that increase synaptic dopamine can cause delusions and hallucinations at high doses
- drugs that block dopamine receptors are effective antipsychotics
the largest population of dopamine neurons are located in the:
midbrain (ventral tegmental area and substantia nigra)
dopamine neurons located in the ventral tegmental area project to the striatum and the prefrontal cortex
mesocortical/mesolimbic system
the mesocortical/mesolimbic system normally mediates:
memory, learning, and thought organization
hyperactivity of the mesocortical/mesolimbic system contributes to:
psychotic symptoms
blocking dopamine transmission is effective at treating:
the positive symptoms of schizophrenia
what type of receptors are dopamine receptors?
GPCRs
what are the two classes of dopamine receptors?
D1 receptors and D2 receptors
class of dopamine receptors which stimulate adeylate cyclase via Gs proteins and subsequently activate cAMP dependent protein kinases
D1 receptors
class of dopamine receptors coupled to Gi proteins and inhibit the activity of adenylate cyclase
D2 receptors
which class of dopamine receptors is directly related to clinical anti-psychotic potency?
D2 receptors (D1 are unlikely to contribute to therapeutic actions of anti-psychotics)
dopamine neurons in the substantia nigra that project to the striatum?
nigrostriatal system
the nigrostriatal system is normally involved in:
movement initiation
inhibiting the nigrostriatal pathways is involved in the production of:
extrapyramidal symptoms (movement disorders)
what is one of the most common examples of extrapyramidal symptoms?
tardive dyskinesias (involuntary movements of the face and mouth)
dopamine neurons neurons in the arcuate nucleus that control hormone release in the pituitary
tuberoinfundibular system
normally, the tuberoinfundibular system inhibits the secretion of:
prolactin and growth hormone
long-terms use of some anti-psychotics is associtated with _____ due to interactions with the tuberoinfundibular system
hyperprolactinemia (increased prolactin release)
what is the glutamate hypothesis?
symptoms of schizophrenia linked to deficiencies in glutamate signalling, particularly in the cortex
what is the major piece of evidence for the glutamate hypothesis?
the effects of phencyclidine and ketamine, which are NMDA antagonists that produce hallucinations and paranoid delusions
the current idea behind the glutamate hypothesis is that schizophrenia is associated with hypofunctional _____ in the cerebral cortex. this hypofunction leads to _____ to the ventral tegmental area
NMDA receptors on GABA interneurons, overactivation of downstream glutamate signalling
what is the serotonin hypothesis?
symptoms of schizophrenia are due to increased serotonin signalling
what are the two major pieces of evidence for the serotonin hypothesis?
- some 5-HT agonists are hallucinogenic (ie: LSD)
- 5-HT antagonists improve positive symptoms of schizophrenia
the current idea behind the serotonin hypothesis is that activation of 5HT-2a receptors in the prefrontal cortex cause hallucinations by:
enhancing excitation of glutamate neurons (activating the mesolimbic dopamine system)
what are the two major classes of anti-psychotic drugs?
- first generation antipsychotics (typical antipsychotics)
- second generation antipsychotics (atypical antipsychotics)
targets both classes of dopamine receptors (D1 and D2), but efficacy particularly relates to D2 receptor antagonism
first generation antipsychotics
what are two examples of first generation antipsychotics?
haloperidol and chlorpromazine
antagonists at both 5HT receptors and D2 receptors
second generation antipsychotics
what are two examples of second generation antipsychotics?
clozapine and risperidone
what makes second generation antipsychotics different from first generation antipsychotics?
they bind looser to dopamine receptors (lower affinity) and produce less dopamine related side effects
how many D2 receptors have to be occupied in order to produce an antipsychotic effect for both typical and atypical antipsychotics?
between 60-80%
about 80% of D2 receptor occupancy results in side effects such as:
Parkinson-like side effects (extrapyramidal symptoms), and elevated prolactin (hyperprolactinemia)
what is the neuroleptic threshold?
the dose of a drug that causes movement side effects
go review slide 733
:P
which antipsychotics exhibit fast on, slow off kinetics?
haloperidol
for haloperidol, the fast on rate results in a high receptor binding potential at D2 in the:
striatum/cortex and pituitary
what side effects are associated with fast on, slow off compounds?
high extrapyramidal side effects and increased prolactin release
which antipsychotics exhibit fast on, fast off kinetics?
chlorpromazine
what side effects are associated with fast on, fast off compounds?
fast on = high extrapyramidal symptoms
fast off = prolactin release stays normal
which antipsychotics exhibit slow on, fast off kinetics?
clozapine or risperidone
what side effects are associated with slow on, fast off compounds?
slow on = extrapyramidal symptoms
fast off = prolactin release stays normal
clozapine has a unique affinity for ____, and causes serious side effects called ____
dopamine D4 receptors, agranulocytosis (loss of white blood cells)
is clozapine still a first line therapy for schizophrenia?
no
how long does it take for anti-psychotics to reach their full effect?
4-6 weeks
what percent of people with schizophrenia are treatment resistant?
~30%
what are the major side effects associated with first generation antipsychotics?
extrapyramidal symptoms, dyskinesias, and prolactin release
what are the major side effects associated with second generation antipsychotics?
cardiovascular effects, metabolic syndrome, diabetes, and weight gain
