• more related to mood disturbance, apathy, anhedonia, neuroleptic
dysphoria, cognitive blunting
• Mesocortical/prefrontal cortex, nucleus accumbens, reward circuit
origins
• Medications: None FDA indicated. Least likely to help are first
generations r/t lack of 5HT2A action.
Cognitive symptoms:
• Attention issues, learning, problem solving, modulating behavior based
on social cues, verbal fluency
• Dorsolateral prefrontal cortex origin
• Medications:
2. Identify the emerging neurobiological hypothesis of schizophrenia.
Dopamine Hypothesis:
• Hyperactivity of dopamine in mesolimbic pathway;
• Mesocortical pathway hypoactivity of dopamine
Glutamate Hypothesis:
• NMDA receptor hypofunction/dysconnectivity on GABA interneuron
o NMDA receptor needs glycine and glutamate
• Possible issue with neurodevelopment/degeneration
• Glutamate hypothesis leads to downstream overactivity of dopamine in
mesolimbic, underactive mesocortical
Serotonin Hypothesis
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• Serotonin hyperfunction
o Hallucinogen psychosis
o Parkinson’s Psychosis = over-production of 5HT2A receptors
o Psychosis in dementia = over-excitation/unclear-inhibition
• 5HT2A receptor hyperfunction in cortex
o Agonism of 5HT2A, some 5HT2C
o Visual hallucinations, mystical delusions, insightfulness
• Serotonin production
o Tryptophan transporter
• Serotonin destroyed via MAO enzyme
• Neurodegeneration process that destroys GABA interneurons creating
imbalance between serotonin and BABA neurotransmission at
glutamate neurons in cerebral cortex
o May lead to excessive activation of glutamate neurons via 5HT
binding at 5HT2A receptors
• 5HT2a receptors are targets for drugs to treat psychosis in Parkinson’s
and dementia
3. Identify the different dopamine pathways and what role each
pathway plays in relation to schizophrenia/psychosis and treatment.
Dopaminergic Pathways
• Mesolimbic – (Ventral tegmental area to nucleus accumbens) –
overactive, too much dopamine activation of dopaminergic neurons =
positive symptoms
• Mesocortical – (VTA to Cortex) – underactive dopamine from VTA to
cortex = negative symptoms
• Nigrostriatal – [substantia nigra to striatum (including caudate +
putamen)] – decreased dopamine causes drug-induced Parkinsonism,
EPS
• Tuberoinfundibular – (dopaminergic neurons to hypothalamus
inhibits prolactin release from pituitary gland) – decreased dopamine
disinhibits the hypothalamus causing increased prolactin resulting in
galactorrhea and amenorrhea (decrease FSH)
4. Identify potential medical emergencies associated with
antipsychotic medications and how to manage these emergencies.
Agranulocytosis/severe neutropenia (<500): discontinue clozapine, daily
CBC, heme consult if not resolved
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