Decreased Frontal Serotonin2A Receptor Binding in Antipsychotic-Naive Patients With First-Episode Schizophrenia

Rasmussen, Henrik; Erritzoe, David; Andersen, Rune; Ebdrup, Bjørn H; Aggernæs, Bodil; Oranje, Bob; Kalbitzer, Jan; Madsen, Jacob; Pinborg, Lars H.; Baaré, William F.C.; Svarer, Claus; Lublin, Henrik; Knudsen, Gitte M.; Glenthøj, Birte

doi:10.1001/archgenpsychiatry.2009.176

Cited by 102 publications

(77 citation statements)

References 60 publications

(75 reference statements)

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“…Thus, changes in HTR2A expression levels in postmortem brain have been detected in schizophrenia [18][19][20]. In line with these findings, a recent meta-analysis confirmed a significant association of the rs6311 HTR2A polymorphism with schizophrenia [21].…”

Section: Discussionsupporting

confidence: 54%

Region-Specific Regulation of the Serotonin 2a Receptor Expression in Development and Aging in Postmortem Human Brain

Marinova

Monoranu

Fetz

et al. 2016

European Neuropsychopharmacology

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AIMS The serotonin 2A receptor (HTR2A) is widely expressed in the brain and involved in the modulation of fear, mood, anxiety and other symptoms. HTR2A and HTR2A gene variations are implicated in depression, schizophrenia, anxiety and obsessive-compulsive disorder. To understand HTR2A signalling changes in psychiatric or neurodegenerative disorders, its normal pattern of brain expression and region specificity during development and aging needs to be clarified. The aim of the present study was to assess HTR2A expression through developmental and aging stages in six brain regions in postmortem human brain samples from individuals with no clinical or neuropathological evidence of neuropsychiatric disorders and to investigate the interaction with the rs6311 HTR2A promoter polymorphism. METH-ODS DNA, RNA and protein were isolated from postmortem brain samples including six regions (frontal cortex, striatum, amygdala, thalamus, brain stem and cerebellum) from 55 individuals. HTR2A mRNA levels were assessed using quantitative real time RT-PCR, and HTR2A protein levels -with western blot. The rs6311 HTR2A polymorphism was analyzed with genotyping. RESULTS We found that HTR2A mRNA and protein levels are differentially regulated with age in different brain regions studied, but are not affected by gender. Significant changes in HTR2A expression with age were found in frontal cortex, amygdala, thalamus, brain stem, and cerebellum. CONCLUSIONS Our results show plasticity and region specificity of HTR2A expression regulation in human brain with age, which may be important for the interaction with other neurotransmitter systems and for the occurrence of developmental periods with increased vulnerability to neuropsychiatric or neurodegenerative disorders. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/nan.12167 Accepted ArticleThis article is protected by copyright. All rights reserved. Significant changes in HTR2A expression with age were found in frontal cortex, amygdala, thalamus, brain stem, and cerebellum. Conclusions: Our results show plasticity and region specificity of HTR2A expression regulation in human brain with age, which may be important for the interaction with other neurotransmitter systems and for the occurrence of developmental periods with increased vulnerability to neuropsychiatric or neurodegenerative disorders.

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Section: Discussionsupporting

confidence: 54%

Region-Specific Regulation of the Serotonin 2a Receptor Expression in Development and Aging in Postmortem Human Brain

Marinova

Monoranu

Fetz

et al. 2016

European Neuropsychopharmacology

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“…Women were excluded from the current study because PPI fluctuates through the menstrual cycle. 32 All participants underwent a comprehensive examination program, including psychopathological ratings, psychophysiological 5,33,34 and neuropsychological examinations, 35,36 singlephoton emission computed tomography (SPECT) 37 or positron emission tomography, 38,39 structural MRI 40,41 and fMRI. 42 We report only on the combined PPI and structural MRI data.…”

Section: Participantsmentioning

confidence: 99%

Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

Hammer

Oranje

Skimminge

et al. 2013

J Psychiatry Neurosci

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“…Eleven out of 15 published post-mortem studies report that serotonin2A receptor binding is decreased in cortical, and especially frontal cortical brain regions (see (Rasmussen et al 2010) for references), although these reports are primarily based on chronically ill, medicated patients, and the techniques used to analyze post-mortem tissue differed between studies (Dean et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine

et al. 2010

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Taken together, the data point to a therapeutic role of the serotonin2A receptor in the treatment of subgroups of patients with schizophrenia. Specifically, the study indicates a serotonin2A receptor associated therapeutic window on positive symptoms in responding patients in the range between 60% and 70% occupancy in antipsychotic-naïve first-episode schizophrenia. We speculate that non-responding patients need higher dopamine D(2) receptor blockade. Future studies with concurrent measurement of interactions with the dopamine system are, however, warranted to clarify this.

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Decreased Frontal Serotonin2A Receptor Binding in Antipsychotic-Naive Patients With First-Episode Schizophrenia

Abstract: clinicaltrials.gov Identifier: NCT00207064.

Cited by 102 publications

References 60 publications

Region-Specific Regulation of the Serotonin 2a Receptor Expression in Development and Aging in Postmortem Human Brain

Region-Specific Regulation of the Serotonin 2a Receptor Expression in Development and Aging in Postmortem Human Brain

Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine

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