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.
| Original language | English |
|---|---|
| Article number | 4 |
| Journal | Translational Neurodegeneration |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Feb 1 2019 |
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Keywords
- 5-HTTLPR
- Alzheimer's disease
- Delusions
- Neuropsychiatric inventory
- Serotonin
ASJC Scopus subject areas
- Clinical Neurology
- Cognitive Neuroscience
- Cellular and Molecular Neuroscience
Cite this
Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer's disease. / D'Onofrio, Grazia; Panza, Francesco; Sancarlo, Daniele; Lauriola, Michele; Dagostino, Mariangela P.; Paroni, Giulia; Lozupone, Madia; Mangiacotti, Antonio; Bisceglia, Paola; Gravina, Carolina; Urbano, Maria; Addante, Filomena; Paris, Francesco; Cascavilla, Leandro; Greco, Antonio; Seripa, Davide.
In: Translational Neurodegeneration, Vol. 8, No. 1, 4, 01.02.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer's disease
AU - D'Onofrio, Grazia
AU - Panza, Francesco
AU - Sancarlo, Daniele
AU - Lauriola, Michele
AU - Dagostino, Mariangela P.
AU - Paroni, Giulia
AU - Lozupone, Madia
AU - Mangiacotti, Antonio
AU - Bisceglia, Paola
AU - Gravina, Carolina
AU - Urbano, Maria
AU - Addante, Filomena
AU - Paris, Francesco
AU - Cascavilla, Leandro
AU - Greco, Antonio
AU - Seripa, Davide
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - 5-HTTLPR
KW - Alzheimer's disease
KW - Delusions
KW - Neuropsychiatric inventory
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=85060894251&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060894251&partnerID=8YFLogxK
U2 - 10.1186/s40035-019-0144-1
DO - 10.1186/s40035-019-0144-1
M3 - Article
AN - SCOPUS:85060894251
VL - 8
JO - Translational Neurodegeneration
JF - Translational Neurodegeneration
SN - 2047-9158
IS - 1
M1 - 4
ER -