Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer’s disease

Abstract Background Serotoninergic pathways underlying delusion symptoms in Alzheimer’s disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-g...

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Main Authors: Grazia D’Onofrio, Francesco Panza, Daniele Sancarlo, Michele Lauriola, Mariangela P. Dagostino, Giulia Paroni, Madia Lozupone, Antonio Mangiacotti, Paola Bisceglia, Carolina Gravina, Maria Urbano, Filomena Addante, Francesco Paris, Leandro Cascavilla, Antonio Greco, Davide Seripa
Format: Article
Language:English
Published: BMC 2019-02-01
Series:Translational Neurodegeneration
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Online Access:http://link.springer.com/article/10.1186/s40035-019-0144-1
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author Grazia D’Onofrio
Francesco Panza
Daniele Sancarlo
Michele Lauriola
Mariangela P. Dagostino
Giulia Paroni
Madia Lozupone
Antonio Mangiacotti
Paola Bisceglia
Carolina Gravina
Maria Urbano
Filomena Addante
Francesco Paris
Leandro Cascavilla
Antonio Greco
Davide Seripa
author_facet Grazia D’Onofrio
Francesco Panza
Daniele Sancarlo
Michele Lauriola
Mariangela P. Dagostino
Giulia Paroni
Madia Lozupone
Antonio Mangiacotti
Paola Bisceglia
Carolina Gravina
Maria Urbano
Filomena Addante
Francesco Paris
Leandro Cascavilla
Antonio Greco
Davide Seripa
author_sort Grazia D’Onofrio
collection DOAJ
description Abstract Background Serotoninergic pathways underlying delusion symptoms in Alzheimer’s disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription. Methods We investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer’s Association criteria. All participants underwent a comprehensive evaluation with a standardized comprehensive geriatric assessment and Neuropsychiatric Inventory. Results Delusion symptoms were observed in 171 patients (66.54%). In respect to AD patients without delusions, AD patients with delusions showed a low prevalence of S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes) [p < 0.001; odds ratio (OR) = 0.240, 95% confidence interval (CI) = 0.121–0.471]. Logistic regression analysis adjusted for the apolipoprotein E polymorphism showed that in AD patients with delusions the presence of an 5-HTTLPR-S allele may reduce disease duration (p = 0.005; OR = 0.680, 95% CI = 0.522–0.886) and increase aberrant motor activity (p = 0.013; OR = 2.257, 95% CI = 1.195–4.260). The present findings suggested that 5-HTTLPR might be associated with delusions in AD. S-plus carriers might be associated with protective effect against delusions in AD. Conclusions More studies on wider samples of high selected demented patients are needed to confirm our results. However, the present findings suggested that a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of neuropsychiatric clusters in AD with important implications regarding mechanisms underlying delusions and their possible treatment across the AD and dementia spectrum.
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spelling doaj.art-1c77b247e3e5494e85111d583b9c3ed72022-12-22T00:19:57ZengBMCTranslational Neurodegeneration2047-91582019-02-018111010.1186/s40035-019-0144-1Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer’s diseaseGrazia D’Onofrio0Francesco Panza1Daniele Sancarlo2Michele Lauriola3Mariangela P. Dagostino4Giulia Paroni5Madia Lozupone6Antonio Mangiacotti7Paola Bisceglia8Carolina Gravina9Maria Urbano10Filomena Addante11Francesco Paris12Leandro Cascavilla13Antonio Greco14Davide Seripa15Fondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitNeurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo MoroFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitFondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics UnitAbstract Background Serotoninergic pathways underlying delusion symptoms in Alzheimer’s disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription. Methods We investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer’s Association criteria. All participants underwent a comprehensive evaluation with a standardized comprehensive geriatric assessment and Neuropsychiatric Inventory. Results Delusion symptoms were observed in 171 patients (66.54%). In respect to AD patients without delusions, AD patients with delusions showed a low prevalence of S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes) [p < 0.001; odds ratio (OR) = 0.240, 95% confidence interval (CI) = 0.121–0.471]. Logistic regression analysis adjusted for the apolipoprotein E polymorphism showed that in AD patients with delusions the presence of an 5-HTTLPR-S allele may reduce disease duration (p = 0.005; OR = 0.680, 95% CI = 0.522–0.886) and increase aberrant motor activity (p = 0.013; OR = 2.257, 95% CI = 1.195–4.260). The present findings suggested that 5-HTTLPR might be associated with delusions in AD. S-plus carriers might be associated with protective effect against delusions in AD. Conclusions More studies on wider samples of high selected demented patients are needed to confirm our results. However, the present findings suggested that a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of neuropsychiatric clusters in AD with important implications regarding mechanisms underlying delusions and their possible treatment across the AD and dementia spectrum.http://link.springer.com/article/10.1186/s40035-019-0144-1DelusionsNeuropsychiatric inventoryAlzheimer’s disease5-HTTLPRSerotonin
spellingShingle Grazia D’Onofrio
Francesco Panza
Daniele Sancarlo
Michele Lauriola
Mariangela P. Dagostino
Giulia Paroni
Madia Lozupone
Antonio Mangiacotti
Paola Bisceglia
Carolina Gravina
Maria Urbano
Filomena Addante
Francesco Paris
Leandro Cascavilla
Antonio Greco
Davide Seripa
Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer’s disease
Translational Neurodegeneration
Delusions
Neuropsychiatric inventory
Alzheimer’s disease
5-HTTLPR
Serotonin
title Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer’s disease
title_full Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer’s disease
title_fullStr Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer’s disease
title_full_unstemmed Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer’s disease
title_short Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer’s disease
title_sort hydroxytryptamine transporter gene linked polymorphic region 5httlpr is associated with delusions in alzheimer s disease
topic Delusions
Neuropsychiatric inventory
Alzheimer’s disease
5-HTTLPR
Serotonin
url http://link.springer.com/article/10.1186/s40035-019-0144-1
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