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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-02-01

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

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. More... »

PAGES

4

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40035-019-0144-1

DOI

http://dx.doi.org/10.1186/s40035-019-0144-1

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https://app.dimensions.ai/details/publication/pub.1111828762

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30733861


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10 schema:description 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) [<i>p</i> &lt; 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 (<i>p</i> = 0.005; OR = 0.680, 95% CI = 0.522-0.886) and increase aberrant motor activity (<i>p</i> = 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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17 schema:keywords AD patients
18 Aging-Alzheimer's Association criteria
19 Alzheimer's disease
20 Association criteria
21 Delusions-Symptoms
22 E polymorphism
23 Institute
24 Inventory
25 National Institute
26 Neuropsychiatric Inventory
27 aberrant motor activity
28 activity
29 alleles
30 analysis
31 apolipoprotein E polymorphism
32 assessment
33 association
34 carriers
35 clinical expression
36 clusters
37 comprehensive evaluation
38 comprehensive geriatric assessment
39 consecutive patients
40 criteria
41 delusions
42 demented patients
43 dementia spectrum
44 disease
45 disease duration
46 duration
47 effect
48 evaluation
49 expression
50 factors
51 findings
52 gene-linked polymorphic region
53 genetic factors
54 geriatric assessment
55 implications
56 important implications
57 logistic regression analysis
58 low prevalence
59 mechanism
60 metabolism
61 more studies
62 motor activity
63 neuropsychiatric clusters
64 number tandem repeat
65 participants
66 pathway
67 patients
68 polymorphic region
69 polymorphism
70 possible treatment
71 presence
72 present findings
73 prevalence
74 promoter region
75 protective effect
76 protective role
77 region
78 regression analysis
79 repeats
80 respect
81 results
82 role
83 samples
84 serotonin
85 serotonin metabolism
86 serotoninergic pathways
87 spectra
88 standardized comprehensive geriatric assessment
89 study
90 symptoms
91 tandem repeats
92 total
93 transcription
94 transporter gene-linked polymorphic region
95 treatment
96 variable number tandem repeat
97 wide sample
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