Chapter 19: Schizophrenia: Antipsychotic Drugs Flashcards
What is schizophrenia?
Schizophrenia is a chronic psychosis that is characterized by illogical thinking, lack of reasoning, and inability to recognize reality. However, there is no defining cluster of symptoms and there is a great deal of individual variation in presentation. This makes diagnosis difficult.
What are the positive symptoms of schizophrenia?
Positive symptoms are dramatic and are what often lead to diagnosis. These symptoms include:
- hallucinations
- delusions
- disorganized speech
- unusual ways of thinking
- bizarre behaviour
What are the negative symptoms of schizophrenia?
Negative symptoms of schizophrenia are harder to recognize than the positive symptoms and are characterized by a decline in normal function. These symptoms include:
- reduced speech
- flat affect
- loss of motivation
- social withdrawal
- apathy
- anhedonia
What are the cognitive symptoms of schizophrenia?
Deficits or impairment in working memory, executive function, and attention.
How effective are antipsychotics at treating schizophrenia?
Positive symptoms of schizophrenia respond to antipsychotic drug treatment. Negative and cognitive symptoms do not.
What prominent structural abnormalities are observed with schizophrenia?
- cerebral atrophy
- enlargement of ventricles
- smaller basal ganglia, temporal lobe, and hippocampus
- disorganized hippocampal cells
- lack of gliosis indicating developmental error
- abnormal myelination and organization of white matter tracts
What functional abnormalities are observed with schizophrenia?
Hypofrontality (reduced function of the prefrontal cortex) during tasks of working memory, executive function, response inhibition, and planning and strategy.
What is the dopamine/dopamine imbalance hypothesis of schizophrenia?
The dopamine hypothesis suggests that positive symptoms are caused by reduced DA function in mesocortical neurons and excessive function in mesolimbic DA neurons. Negative symptoms are caused by impaired PFC function.
What is the evidence for the dopamine hypothesis of schizophrenia?
- amphetamine produces positive symptoms in healthy individuals and makes symptoms worse in patients with schizophrenia
- intracerebral DA into the forebrain of rodents produces stereotyped behavior reversed by antipsychotics
- a strong correlation exits between D2 receptor blockade and antipsychotic efficacy
- schizophrenic individuals show exaggerated DA release after amphetamine challenge as well as in basal conditions
- increased D2 receptors in people with schizophrenia
What is the evidence for the role of the PFC in negative/cognitive symptoms of schizophrenia?
- the negative/cognitive symptoms resemble characteristics after frontal lobotomy
- the severity of negative symptoms is negatively correlated with prefrontal brain activity and decreased DA function
- prefrontal brain lesions or D1 receptor antagonists injected into PFC impair cognitive performance
What is the neurodevelopmental model of schizophrenia?
The neurodevelopmental model suggests that early mesocortical deficits due to genetics or environmental events that alter brain development are followed by loss of inhibitory control of mesolimbic cells and the onset of positive symptoms.
What is the hypoglutamate model of schizophrenia?
Low glutamate signaling at NMDA receptors (or NMDA receptor antagonist administration) reduces mesocortical function, causing negative/cognitive symptoms.
Low glutamate signaling at NMDA receptors (or NMDA receptor antagonist administration) leads to excessive mesolimbic firing and positive symptoms.
What is meant by a biopsychosocial interaction as a basis for schizophrenia?
Biological, psychological, and sociological factors combine to contribute to the psychopathology, course, and outcome.
First Hit - In early stages of development genetic expression and gene expression influence predisposition. Perinatal environmental insults can lead to neurodevelopmental abnormalities from conception to early adulthood.
Latent Stage - Subtle signs predicting schizophrenia appear
Second Hit - In late stages excessive synaptic pruning in adolescence leads to abnormal neuronal connectivity and function. The factors cause greater cognitive impairment, presentation of positive symptoms and worsening of negative symptoms.
What are patient outcomes on antipsychotics?
One-third of patients treated improve dramatically and return to normal lives.
A second third show some improvement but experience relapses and need help with day-to-day living.
The final third show little improvement and have significant periods of hospitalization.
How do first- and second-generation antipsychotic drugs work?
Antipsychotic drugs competitively block postsynaptic D2 receptors to reduce dopaminergic transmission. They also block D2 autoreceptors which increases the rate of cell firing and increases turnover of dopamine (increased synthesis, release, and metabolism). After an initial increase in dopamine turnover, the autoreceptors up-regulate and there is a gradual decrease in DA turnover. Depolarization block may contribute to the decrease in turnover.
