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

Hans Rasmussen; David Erritzoe; Rune Andersen; Bjorn H Ebdrup; Bodil Aggernaes; Bob Oranje; Jan Kalbitzer; Jacob Madsen; Lars Hageman Pinborg; William Baaré; Claus Svarer; Henrik Lublin; Gitte M Knudsen; Birte Yding Glenthøj

doi:10.1001/archgenpsychiatry.2009.176

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

Hans Rasmussen, David Erritzoe, Rune Andersen, Bjorn H Ebdrup, Bodil Aggernaes, Bob Oranje, Jan Kalbitzer, Jacob Madsen, Lars Hageman Pinborg, William Baaré, Claus Svarer, Henrik Lublin, Gitte M Knudsen, Birte Yding Glenthøj

92 Citations (Scopus)

Abstract

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 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.

Original language	English
Journal	Archives of General Psychiatry
Volume	67
Issue number	1
Pages (from-to)	9-16
Number of pages	8
ISSN	0003-990X
DOIs	https://doi.org/10.1001/archgenpsychiatry.2009.176
Publication status	Published - 1 Jan 2010

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Rasmussen, H., Erritzoe, D., Andersen, R., Ebdrup, B. H., Aggernaes, B., Oranje, B., Kalbitzer, J., Madsen, J., Pinborg, L. H., Baaré, W., Svarer, C., Lublin, H., Knudsen, G. M., & Glenthøj, B. Y. (2010). Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia. Archives of General Psychiatry, 67(1), 9-16. https://doi.org/10.1001/archgenpsychiatry.2009.176

Rasmussen, H, Erritzoe, D, Andersen, R, Ebdrup, BH, Aggernaes, B, Oranje, B, Kalbitzer, J, Madsen, J, Pinborg, LH, Baaré, W, Svarer, C, Lublin, H, Knudsen, GM & Glenthøj, BY 2010, 'Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia', Archives of General Psychiatry, vol. 67, no. 1, pp. 9-16. https://doi.org/10.1001/archgenpsychiatry.2009.176

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title = "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 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.",

author = "Hans Rasmussen and David Erritzoe and Rune Andersen and Ebdrup, {Bjorn H} and Bodil Aggernaes and Bob Oranje and Jan Kalbitzer and Jacob Madsen and Pinborg, {Lars Hageman} and William Baar{\'e} and Claus Svarer and Henrik Lublin and Knudsen, {Gitte M} and Glenth{\o}j, {Birte Yding}",

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doi = "10.1001/archgenpsychiatry.2009.176",

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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

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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.

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DO - 10.1001/archgenpsychiatry.2009.176

M3 - Journal article

SN - 0003-990X

VL - 67

SP - 9

EP - 16

JO - Archives of General Psychiatry

JF - Archives of General Psychiatry

IS - 1

ER -

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

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