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...
Main Authors: | , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-02-01
|
Series: | Translational Neurodegeneration |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s40035-019-0144-1 |
_version_ | 1818249564172320768 |
---|---|
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. |
first_indexed | 2024-12-12T15:38:30Z |
format | Article |
id | doaj.art-1c77b247e3e5494e85111d583b9c3ed7 |
institution | Directory Open Access Journal |
issn | 2047-9158 |
language | English |
last_indexed | 2024-12-12T15:38:30Z |
publishDate | 2019-02-01 |
publisher | BMC |
record_format | Article |
series | Translational Neurodegeneration |
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 |
work_keys_str_mv | AT graziadonofrio hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT francescopanza hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT danielesancarlo hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT michelelauriola hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT mariangelapdagostino hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT giuliaparoni hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT madialozupone hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT antoniomangiacotti hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT paolabisceglia hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT carolinagravina hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT mariaurbano hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT filomenaaddante hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT francescoparis hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT leandrocascavilla hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT antoniogreco hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease AT davideseripa hydroxytryptaminetransportergenelinkedpolymorphicregion5httlprisassociatedwithdelusionsinalzheimersdisease |