Document Detail

Influence of serotonin transporter gene polymorphisms on cognitive decline and cognitive abilities in a nondemented elderly population.
MedLine Citation:
PMID:  16103887     Owner:  NLM     Status:  MEDLINE    
Dysfunction of the serotonergic pathway disrupts normal cognitive functioning and is believed to be the underlying basis for a variety of psychiatric disorders. Two functional polymorphisms within the serotonin transporter (SLC6A4) gene (promoter 44 bp insertion/deletion (HTTLPR) and an intron two 16 or 17 bp variable number tandem repeat (VNTR2)) have been extensively studied in psychiatric conditions but not in the cognitive functioning of normal individuals. We have investigated these two polymorphisms for association with both the level of cognitive abilities and their decline with age using a cohort consisting of over 750 elderly nondemented individuals with a follow-up of up to 15 years. We found that volunteers homozygous for the VNTR2 12 allele had a faster rate of decline for all cognitive tests. This reached significance for both tests of fluid intelligence (novel problem solving) (AH1 P=0.002, AH2 P=0.014), the test of semantic memory (P=0.010) and general cognitive ability (P=0.006). No association was observed between the HTTLPR polymorphism and the rate of cognitive decline when analysed either independently or in combination with the VNTR2 polymorphism based on their influence on expression in vitro. No associations were observed between the two polymorphisms and the baseline level of cognitive abilities. This is only the second gene that has been reported to regulate the rate of cognitive decline in nondemented individuals and may be a target for the treatment of cognitive impairment in the elderly.
A Payton; L Gibbons; Y Davidson; W Ollier; P Rabbitt; J Worthington; A Pickles; N Pendleton; M Horan
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular psychiatry     Volume:  10     ISSN:  1359-4184     ISO Abbreviation:  Mol. Psychiatry     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-28     Completed Date:  2006-03-01     Revised Date:  2007-08-13    
Medline Journal Info:
Nlm Unique ID:  9607835     Medline TA:  Mol Psychiatry     Country:  England    
Other Details:
Languages:  eng     Pagination:  1133-9     Citation Subset:  IM    
Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
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MeSH Terms
Aged, 80 and over
Aging / genetics*,  physiology
Cognition / physiology*
Memory / physiology*
Middle Aged
Minisatellite Repeats / genetics*
Polymorphism, Genetic
Serotonin Plasma Membrane Transport Proteins / genetics*
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/SLC6A4 protein, human; 0/Serotonin Plasma Membrane Transport Proteins

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