Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia.

Abstract

CONTEXT:

Postmortem investigations and the receptor affinity profile of atypical antipsychotics have implicated the participation of serotonin(2A) receptors in the pathophysiology of schizophrenia. Most postmortem studies point toward lower cortical serotonin(2A) binding in schizophrenic patients. However, in vivo studies of serotonin(2A) binding report conflicting results, presumably because sample sizes have been small or because schizophrenic patients who were not antipsychotic-naive were included. Furthermore, the relationships between serotonin(2A) binding, psychopathology, and central neurocognitive deficits in schizophrenia are unclear.

OBJECTIVES:

To assess in vivo brain serotonin(2A) binding potentials in a large sample of antipsychotic-naive schizophrenic patients and matched healthy controls, and to examine possible associations with psychopathology, memory, attention, and executive functions.

DESIGN:

Case-control study.

SETTING:

University hospital, Denmark.

PARTICIPANTS:

A sample of 30 first-episode, antipsychotic-naive schizophrenic patients, 23 males and 7 females, and 30 matched healthy control subjects.

INTERVENTIONS:

Positron emission tomography with the serotonin(2A)-specific radioligand fluorine 18-labeled altanserin and administration of a neuropsychological test battery.

MAIN OUTCOME MEASURES:

Binding potential of specific tracer binding, scores on the Positive and Negative Syndrome Scale, and results of neuropsychological testing.

RESULTS:

Schizophrenic patients had significantly lower serotonin(2A) binding in the frontal cortex than did control subjects. A significant negative correlation was observed between frontal cortical serotonin(2A) binding and positive psychotic symptoms in the male patients. No correlations were found between cognitive functions and serotonin(2A) binding.

CONCLUSION:

The results suggest that frontal cortical serotonin(2A) receptors are involved in the pathophysiology of schizophrenia.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00207064.

• Authors: Hans Rasmussen, David Erritzoe, Rune Andersen, Bjorn H Ebdrup, Bodil Aggernaes, Bob Oranje, Jan Kalbitzer, Jacob Madsen, Lars H Pinborg, William Baaré, Claus Svarer, Henrik Lublin, Gitte M Knudsen, Birte Glenthoj
• Journal: Archives of general psychiatry (Arch Gen Psychiatry) Vol. 67 Issue 1 Pg. 9-16 (Jan 2010) ISSN: 1538-3636 [Electronic] United States
• PMID: 20048218 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Fluorine Radioisotopes
• Receptor, Serotonin, 5-HT2A
• Serotonin
• altanserin
• Ketanserin

Topics

• Adult
• Antipsychotic Agents (adverse effects, therapeutic use)
• Brain (diagnostic imaging, metabolism)
• Case-Control Studies
• Female
• Fluorine Radioisotopes (metabolism)
• Frontal Lobe (diagnostic imaging, metabolism)
• Humans
• Ketanserin (analogs & derivatives, metabolism)
• Male
• Neuropsychological Tests (statistics & numerical data)
• Radionuclide Imaging
• Receptor, Serotonin, 5-HT2A (metabolism, physiology)
• Schizophrenia (diagnosis, diagnostic imaging, drug therapy, physiopathology)
• Serotonin (physiology)