Schizophrenia

Question 1

Schizophrenia General Info

Answer 1

• unknown etiology
• onset between 18-25
• defined by observed psychosis (hallucinations, delusions, paranoia)
• also negative symptoms, cognitive deficits
• risk inc. with close relatives
• not completely genetic -> environmental component (season of birth, prenatal complications, drug use, etc)
• many genes contribute

Question 2

Schizophrenia Brain Changes

Answer 2

• dec. size and density of neurons in prefrontal cortex
• reduced GABAergic interneuron proteins and neuronal function in layer 3 DLPFC
• dec. dendritic spines and presynaptic axonal inputs
• enlarged lateral ventricles
• prefrontal cortex may be under or over active compared to healthy individuals

Question 3

3 Theories of Schizophrenia

Answer 3

• DA theory: hyperactivity of DA in mesolimbic system and hypoactivity of DA in mesocortical system
• Glu theory: hypoactivity of cortical glutamatergic system
• GABAergic Model: reduced parvalbumin positive interneurons in laminar 3 of prefrontal cortex

Question 4

Positive Symptoms of Schizophrenia

Answer 4

• due to overactivity of DA neurons in limbic system
• psychotic symptoms: delusions, hallucinations
• disorganized symptoms: thought disorders

Question 5

Negative Symptoms of Schizophrenia

Answer 5

• due to hypoactivity of DA neurons in the prefrontal cortex
• withdrawl
• flattening of emotional responses
• cognitive symptoms: poor working memory, etc.
• predominant component of chronic schizophrenia

Question 6

Serotonin Hypothesis of Schizophrenia

Answer 6

• 5HT2A receptors on DA neurons in the PFC dec. DA release
• Block of these receptors by by atypical agents results in inc. DA release resulting in alleviation of negative symptoms of schizophrenia

Question 7

Dopamine Hypothesis of Schizophrenia

Answer 7

-abnormality of brain function in schizophrenics is due to overactivity in brain dopaminergic pathways, esp. in mesolimbic pathway

Question 8

Glutimate Hypofunction Hypothesis of Schizophrenia

Answer 8

• cortical Glu neurons activate cortical GABA neurons to produce a tonic inhibition of cortical Glu excitation of mesolimbic DA neurons
• hypofunction in cortical NMDA-Glu neurons remove GABA-> inhibition activate DA neurons -> positive sxs of schizophrenia

Question 9

Positive sxs of schizophrenia are believed to result from:

Answer 9

• overactivity of DA neurons in the mesolimbic system

- underactivity of Glu neurons in the prefrontal cortex

Question 10

Tx for Schizophrenia: Chlorpromazine

Answer 10

• first generation
• primary target of action is DA receptor anagonism (DRD2)
• side effects: dry mouth, muscle, weight gain, parkinsonism, dystonias
• now second gen drugs have fewer undesirable side effects