Psychosis Flashcards
Psychosis definition
Mental disorders involving a loss of contact with reality
Psychosis is the symptom, caused by a variety of psychotic disorders
Schizophrenia symptom types
Positive: phenomena absent in healthy people eg. Hallucinations
Negative: impairment of normal psychological function eg. Social withdrawal, loss of motivation
Cognitive: impairment of concentration, memory, organization of thought, etc
Dopamine hypothesis
Evidence: drugs that increase synaptic dopamine can cause hallucinations and delusions, drugs that block dopamine receptors have antispsychotic effects
Schizophrenia due to hyperactive dopamine system
Dopamine systems
Most dopamine neurons in midbrain
Mesocortical/mesolimbic system: neurons in VTA project to striatum and prefrontal cortex (cognition effects)
Nigrostriatal system: neurons in substantia nigra project to striatum (movement effects)
Tuberoinfundibular system: controls pituitary hormone release
Dopamine receptors
D1: Gs, not antipsychotic target
D2: Gi, blocking produces antisychotic effects
Adverse effects
Extrapyramidal symptoms including tardive dyskinesias: connected to nigrostriatal inhibition, Parkinson’s-like movement disorders
Hyperprolactinemia: connected to tuberoinfundular inhibition, libido and fertility related problems
Glutamate hypothesis
Evidence: NMDA antagonists (PCP, Ketamine) can produce schizophrenia-like effects
Hypofunctional NMDA receptors on GABA interneurons in cerebral cortex, leads to overactivation of downstream glutamate signaling to VTA
Serotonin hypothesis
Evidence: some 5HT agonists are hallucinogenic, 5HT antagonists reduce positive symptoms
Activation of 5HT-2A receptors enhance excitation of glutamate neurons, which increases activation of the mesolimbic dopamine system
First Gen antipsychotics (typical)
Dopamine receptor blockers, potency related to D2 blocking
Haloperidol, chlopromazine
2nd Gen antipsychotics (atypical)
Mostly 5HT and D2 antagonists
Lower D1/D2 affinity, less dopamine side effects
Clozapine, risperidone
Kinetic hypothesis (dopamine side effects)
Mesolimbic/nigrostriatal pathway: synaptic release, high rebinding (pond)
Tuberoinfundibular pathway: bloodstream release, low rebinding (river)
Connection between binding/release speed and side effects
Slow on: low rebinding, low extrapyramidal effects (affects mesolimbic/nigrostriatal systems)
Fast off: normal prolactin release (affects tuberoinfundibular system)
Clozapine side effect
Agranulocytosis (loss of WBCs) caused by unique D4 affinity
Side effects by generation
1st: extrapyramidal symptoms, dyskinesias, elevated prolactin
2nd: cardiovascular effects, weight gain, diabetes
