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Probing the human hippocampus using rCBF: contrasts in schizophrenia
D R Medoff1, H H Holcomb, A C Lahti
1Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228, USA.
Hippocampus
|December 6, 2001
Summary
Schizophrenia is linked to higher hippocampal blood flow, which improves with antipsychotic medication. Ketamine further reduced this blood flow in schizophrenic patients, suggesting NMDA receptor involvement in the illness.
Area of Science:
- Neuroscience
- Psychiatry
- Radiology
Background:
- Schizophrenia is a complex psychiatric disorder with debated pathophysiology.
- Hippocampal dysfunction is implicated in schizophrenia.
- Regional cerebral blood flow (rCBF) is a marker of brain activity.
Purpose of the Study:
- To investigate hippocampal rCBF in schizophrenia.
- To examine the effects of ketamine and antipsychotic medication on hippocampal rCBF in schizophrenia.
- To explore the relationship between NMDA receptor function and hippocampal activity in schizophrenia.
Main Methods:
- Positron Emission Tomography (PET) with 15O-water was used to measure rCBF.
- Magnetic Resonance (MR)-guided hippocampal volumes of interest (VOIs) were analyzed.
- Two studies compared normal volunteers and schizophrenic patients under various conditions, including drug (ketamine, antipsychotics) and placebo.
Main Results:
- Schizophrenic patients exhibited higher hippocampal rCBF than normal volunteers, independent of task conditions.
- Unmedicated schizophrenic patients had higher resting hippocampal rCBF than medicated patients and normal controls.
- Ketamine, an NMDA receptor antagonist, more potently reduced hippocampal rCBF in schizophrenic patients compared to normal volunteers.
Conclusions:
- Schizophrenia is associated with elevated hippocampal rCBF, which may normalize with antipsychotic treatment.
- These findings suggest abnormal hippocampal function and NMDA receptor involvement in schizophrenia pathophysiology.
- Hippocampal rCBF alterations may serve as a biomarker for schizophrenia and its treatment response.