TY - JOUR
T1 - Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia
AU - Rasmussen, Hans
AU - Erritzoe, David
AU - Andersen, Rune
AU - Ebdrup, Bjorn H
AU - Aggernaes, Bodil
AU - Oranje, Bob
AU - Kalbitzer, Jan
AU - Madsen, Jacob
AU - Pinborg, Lars Hageman
AU - Baaré, William
AU - Svarer, Claus
AU - Lublin, Henrik
AU - Knudsen, Gitte M
AU - Glenthøj, Birte Yding
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Context: Postmortem investigations and the receptor affinity profile of atypical antipsychotics have implicated the participation of serotonin 2A receptors in the patho-physiology of schizophrenia. Most postmortem studies point toward lower cortical serotonin2A binding in schizophrenic patients. However, in vivo studies of serotonin2A 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 serotonin2A binding, psychopathology, and central neurocognitive deficits in schizophrenia are unclear. Objectives: To assess in vivo brain serotonin2A 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 serotonin2A-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 serotonin2A binding in the frontal cortex than did control subjects. A significant negative correlation was observed between frontal cortical serotonin2A binding and positive psychotic symptoms in the male patients. No correlations were found between cognitive functions and serotonin2A binding. Conclusion: The results suggest that frontal cortical serotonin2A receptors are involved in the pathophysiology of schizophrenia. Trial Registration: clinicaltrials.gov Identifier: NCT00207064.
AB - Context: Postmortem investigations and the receptor affinity profile of atypical antipsychotics have implicated the participation of serotonin 2A receptors in the patho-physiology of schizophrenia. Most postmortem studies point toward lower cortical serotonin2A binding in schizophrenic patients. However, in vivo studies of serotonin2A 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 serotonin2A binding, psychopathology, and central neurocognitive deficits in schizophrenia are unclear. Objectives: To assess in vivo brain serotonin2A 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 serotonin2A-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 serotonin2A binding in the frontal cortex than did control subjects. A significant negative correlation was observed between frontal cortical serotonin2A binding and positive psychotic symptoms in the male patients. No correlations were found between cognitive functions and serotonin2A binding. Conclusion: The results suggest that frontal cortical serotonin2A receptors are involved in the pathophysiology of schizophrenia. Trial Registration: clinicaltrials.gov Identifier: NCT00207064.
U2 - 10.1001/archgenpsychiatry.2009.176
DO - 10.1001/archgenpsychiatry.2009.176
M3 - Journal article
SN - 2168-622X
VL - 67
SP - 9
EP - 16
JO - JAMA Psychiatry
JF - JAMA Psychiatry
IS - 1
ER -