Lecture 12 Schizophrenia and Antipsychotics Flashcards
What percent of the worlds population has schizophrenia?
1%
1/3 of homeless people have schizophrenia
When is the onset of schizophrenia?
Late adolescence and early adulthood suggesting a developmental factor
What is the ratio of male to female that have schizophrenia?
1.4(M)/1(F)
Males tend to show symptoms earlier
likely a result of gene x environment interactions
Name 5 subtypes of schizophrenia
Paranoid Catatonic Disorganized Undifferentiated Residual
What is the primary symptom of paranoid schizophrenia?
Delusions
What is the primary symptom of catatonic schizophrenia?
Immobility
What is the primary symptom of disorganized schizophrenia?
Inappropriate emotional expression, immaturity
What is the primary symptom of of undifferentiated schizophrenia?
no specific pattern of symptoms
What is the primary symptom of residual schizophrenia?
Spontaneous remission of symptoms
What are the positive symptoms of schizophrenia?
Hallucinations, delusions of persecution and grandeur, bizarre behavior.
What are the negative symptoms of schizophrenia?
Social withdrawal, anhedonia, decreased mobility, flat affect, poor hygiene
What are cognitive deficits of schizophrenia?
Deficits in working memory, reference memory, attention and executive functioning
What are some brain abnormalities in schizophrenia?
Enlarged cerebral ventricles, neuronal disorganization, accelerated loss of cortical grady matter during adolescence
What is the dopamine hypothesis of schizophrenia?
Overactivation of mesolimbic dopamine circuitry is thought to underlie positive symptoms of schizophrenia.
What is the dopamine hypothesis based on?
Antipsychotics block dopamine receptors, primarily D2 receptors
What is the revised dopamine hypothesis of schizophrenia?
Hypoactivation of mesocortical dopamine circuitry is thought to underlie negative and cognitive symptoms of schizophrenia
other dopamine circuits are thought to function normally
What is the glutamate hypothesis of schizophrenia?
Mesolimbic dopamine neurons are tonically activated by glutamate neurons in the frontal cortex that activate GABA interneurons in the VTA
Hypofunction of NMDA receptors on GABA interneurons causes less activation, releasing the brake on mesolimbic dopamine neurons resulting in overactivity and psychotic symptoms
What is the glutamate hypothesis based on?
NMDA receptor blockers (PCP, ketamine) produces schizophrenia like symptoms in humans
What are the 2 classes of glutamate receptors?
Ionotropic: Ligand gated ion channels (NMDA, AMPA and Kainate)
mesotropic: G-protein couple receptors (mGluR)
What is the NMDA receptor critical for?
Synaptic plasticity and has binding sites for many molecules and ions
What is the excitotoxicity hypothesis of schizophrenia?
During brain development, excessive calcium influx through NMDA receptors causes the production of free radicals which cause excitotoxicity, neurodegeneration and abnormal brain development
What are antipsychotics also known as?
Neuroleptics
Name 6 typical antipsychotics
chlorpromazine thioridazine loxapine perphenazine haloperidol (Haldol) fluphenazine,
Name 6 2nd generation or atypical antipsychotics
clozapine (Clozaril) olanzapine (Zyprexa) quetiapine (Seroquel) risperidone (Risperdal) ziprasidone (Geodon), aripiprazole (Abilify),
How do typical antipsychotics work?
Blocking D2 receptors
How do 2nd generation or atypical antipsychotics work?
In addition to block D2 receptors, they also have antagonistic or inverse agonist properties at 5-HT2S receptors
What are the extrapyramidal side effects of antipsychotic medications?
involuntary and repetitive movements such as tardive dyskinesia, due to blockade of D2 receptors in striatum
What are the cholinergic side effects of antipsychotic medications?
Blurred vision, constipation, drowsiness and dry mouth due to M1 muscarinic receptor antagonism
Explain why drowsiness and weight gain occurs with antipsychotics
H1 histamine receptor antagonism
Explain why hypotension and dizziness occurs with antipsychotics
Due to alpha1 noradrenergic receptor antagonism
