Week 6: Glutamate and dopamine in schizophrenia: An update for the 21st century Flashcards
What is schizophrenia?
Schizophrenia is a common, severe mental illness characterized by psychotic symptoms such as delusions and hallucinations, negative symptoms such as social withdrawal, and cognitive impairments.
What are the two main hypotheses concerning schizophrenia?
The dopamine and glutamate hypotheses.
How was dopamine initially linked to schizophrenia?
Studies showed that amphetamine, which increases dopamine, can induce psychotic symptoms, and drugs that deplete dopamine reduce psychotic symptoms.
What did post-mortem studies reveal about dopamine in schizophrenia?
They suggested increased striatal dopamine levels and D2 receptor density, but no change in dopamine transporter densities.
What imaging techniques are used to study dopamine in schizophrenia?
Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT).
What is the estimated lifetime prevalence of schizophrenia?
About 0.7%, with peak onset in the early twenties for men and later for women.
What is the estimated annual cost of schizophrenia care in the UK and Europe?
16.7 billion EURO in the UK and 93.9 billion EURO in Europe.
Why are antipsychotic drugs considered inadequate for some schizophrenia patients?
Because they do not work effectively for a substantial proportion of patients.
What early evidence supported the dopamine hypothesis of schizophrenia?
The clinical effectiveness of antipsychotics was found to be directly related to their affinity for dopamine receptors.
What is the primary function of dopamine D2 receptors in schizophrenia treatment?
They are blocked by all currently licensed antipsychotic drugs to reduce psychotic symptoms.
What did PET and SPECT imaging reveal about dopamine in schizophrenia?
They demonstrated increased dopamine synthesis and release in patients compared to controls.
What is the role of the dopamine transporter (DAT) in schizophrenia?
DAT regulates dopaminergic transmission, but studies have found no significant difference in DAT levels between patients and controls.
How does dopamine synthesis capacity differ in schizophrenia?
It is significantly elevated in first-episode psychosis patients compared to healthy controls.
What is the aberrant salience hypothesis?
It proposes that dysregulated dopamine release leads to the attribution of salience to irrelevant stimuli, contributing to psychotic symptoms.
What evidence supports the glutamate hypothesis of schizophrenia?
NMDA receptor antagonists like PCP and ketamine induce psychotic-like symptoms, suggesting NMDA receptor hypofunction.
What post-mortem findings support the glutamate hypothesis?
Reduced NMDA receptor subunit density has been found in the superior frontal and temporal cortex of schizophrenia patients.
How do NMDA receptor antagonists affect schizophrenia symptoms?
They mimic both positive and negative symptoms of schizophrenia.
What role does the thalamus play in NMDA receptor dysfunction in schizophrenia?
Injection of NMDA receptor antagonists into the thalamus causes cortical changes similar to schizophrenia pathology.
What imaging method is used to study glutamate levels in schizophrenia?
Proton magnetic resonance spectroscopy (1H-MRS) is commonly used to measure glutamate and glutamine levels.
What is the relationship between glutamate levels and schizophrenia?
Elevated glutamate levels are often found in individuals at high risk of psychosis and in first-episode psychosis patients.
What is the significance of treatment-resistant schizophrenia in the dopamine hypothesis?
Patients with treatment-resistant schizophrenia often do not show the expected presynaptic dopamine abnormalities.
How do environmental factors contribute to schizophrenia according to the dopamine hypothesis?
Stress and other risk factors may dysregulate a vulnerable dopamine system, leading to psychosis.
What is the relationship between schizophrenia and cognitive symptoms?
Increased striatal dopamine synthesis is associated with worse cognitive performance.
What drugs have been tested as glutamatergic treatments for schizophrenia?
D-serine, glycine transport inhibitors, minocycline, and NMDA receptor modulators have been tested with mixed results.
What is the potential link between schizophrenia and substance dependence?
Substance abuse, such as cannabis use, may involve a distinct pathway from the striatal presynaptic dopamine dysfunction seen in schizophrenia.
