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Hans Rasmussen, PhD; David Erritzoe, MD, PhD; Rune Andersen, MSc; Bjorn H. Ebdrup, MD; Bodil Aggernaes, MD, PhD; Bob Oranje, PhD; Jan Kalbitzer, MD; Jacob Madsen, PhD; Lars H. Pinborg, MD, DMSc; William Baaré, PhD; Claus Svarer, PhD; Henrik Lublin, MD, DMSc; Gitte M. Knudsen, MD, DMSc; Birte Glenthoj, MD, DMSc

Arch Gen Psychiatry. 2010;67(1):9-16.

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

Author Affiliations: Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Faculty of Health Sciences, Copenhagen University Hospital, Psychiatric University Center Glostrup, Glostrup, Denmark (Drs Rasmussen, Ebdrup, Aggernaes, Oranje, Lublin, and Glenthoj and Mr Andersen); Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Faculty of Health Sciences (Drs Rasmussen, Erritzoe, Kalbitzer, Pinborg, Svarer, and Knudsen), and PET and Cyclotron Unit (Dr Madsen), Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; and Danish Center for Magnetic Resonance Imaging and Center for Integrated Molecular Brain Imaging, Faculty of Health Sciences, Copenhagen University Hospital Hvidovre Hospital, Hvidovre, Denmark (Dr Baaré).

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