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


OBJECTIVE
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.


METHODS
Case-control study.


METHODS
University hospital, Denmark.


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


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


METHODS
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.


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


BACKGROUND
clinicaltrials.gov Identifier: NCT00207064.
Rasmussen
Hans
H
Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Faculty of Health Sciences, Copenhagen University Hospital, Psychiatric University Center Glostrup, Glostrup, Denmark. h.rasmussen@cnsr.dk
Erritzoe
David
D
Andersen
Rune
R
Ebdrup
Bjorn H
BH
Aggernaes
Bodil
B
Oranje
Bob
B
Kalbitzer
Jan
J
Madsen
Jacob
J
Pinborg
Lars H
LH
Baaré
William
W
Svarer
Claus
C
Lublin
Henrik
H
Knudsen
Gitte M
GM
Glenthoj
Birte
B
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011877:Radionuclide Imaging; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism* / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D012701:Serotonin / Q000502:physiology
D014150:Antipsychotic Agents; D005462:Fluorine Radioisotopes; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; C071983:altanserin; D007650:Ketanserin