Dataset Information

Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities.

ABSTRACT: Human memory and general cognitive abilities are complex functions of high heritability and wide variability in the population. The brain-derived neurotrophic factor (BDNF) plays an important role in mammalian memory formation.Based on the identification of genes markedly up-regulated during BDNF-induced synaptic consolidation in the hippocampus, we selected genetic variants that were tested in three independent samples, from Norway and Scotland, of adult individuals examined for cognitive abilities. In all samples, we show that markers in the doublecortin- and calmodulin kinase like 1 (DCLK1) gene, are significantly associated with general cognition (IQ scores) and verbal memory function, resisting multiple testing. DCLK1 is a complex gene with multiple transcripts which vary in expression and function. We show that the short variants are all up-regulated after BDNF treatment in the rat hippocampus, and that they are expressed in the adult human brain (mostly in cortices and hippocampus). We demonstrate that several of the associated variants are located in potential alternative promoter- and cis-regulatory elements of the gene and that they affect BDNF-mediated expression of short DCLK1 transcripts in a reporter system.These data present DCLK1 as a functionally pertinent gene involved in human memory and cognitive functions.

SUBMITTER: Le Hellard S

PROVIDER: S-EPMC2760101 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities.

Le Hellard Stéphanie S Håvik Bjarte B Espeseth Thomas T Breilid Harald H Løvlie Roger R Luciano Michelle M Gow Alan J AJ Harris Sarah E SE Starr John M JM Wibrand Karin K Lundervold Astri J AJ Porteous David J DJ Bramham Clive R CR Deary Ian J IJ Reinvang Ivar I Steen Vidar M VM

PloS one 20091021 10

<h4>Background</h4>Human memory and general cognitive abilities are complex functions of high heritability and wide variability in the population. The brain-derived neurotrophic factor (BDNF) plays an important role in mammalian memory formation.<h4>Methodology / principal finding</h4>Based on the identification of genes markedly up-regulated during BDNF-induced synaptic consolidation in the hippocampus, we selected genetic variants that were tested in three independent samples, from Norway and ...[more]

PMID: 19844571

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Project description:BACKGROUND:Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different ability measures used previously, focusing on tests of intelligence quotient (IQ) and adaptive behaviour (AB), and where possible examines floor effects and differences between DS subpopulations. We aimed to use information regarding existing measures to provide recommendations for individual researchers and the DS research community. RESULTS:Nineteen studies reporting IQ test data met inclusion for this review, with 17 different IQ tests used. Twelve of these IQ tests were used in only one study while five were used in two different studies. Eleven studies reporting AB test data met inclusion for this review, with seven different AB tests used. The only AB scales to be used by more than one study were the Vineland Adaptive Behaviour Scale (VABS; used by three studies) and the Vineland Adaptive Behavior Scale 2nd Edition (VABS-II; used by two studies). A variety of additional factors were identified which make comparison of test scores between studies problematic, including different score types provided between studies (e.g. raw scores compared to age-equivalent scores) and different participant inclusion criteria (e.g. whether individuals with cognitive decline were excluded). Floor effects were common for IQ tests (particularly for standardised test scores). Data exists to suggest that floor effects may be minimised by the use of raw test scores rather than standardised test scores. Raw scores may, therefore, be particularly useful in longitudinal studies to track change in cognitive ability over time. CONCLUSIONS:Studies assessing general ability in adults with DS are likely to benefit from the use of both IQ and AB scales. The DS research community may benefit from the development of reporting standards for IQ and AB data, and from the sharing of raw study data enabling further in-depth investigation of issues highlighted by this review.

Project description:ObjectiveVery preterm (<32 weeks gestation; VP) and/or very low birth weight (<1500g; VLBW) children often have cognitive and mathematic difficulties. It is unknown whether VP/VLBW children's frequent mathematic problems significantly add to the burden of negative life-course consequences over and above effects of more general cognitive deficits. Our aim was to determine whether negative consequences of VP/VLBW versus healthy term birth on adult wealth are mediated by mathematic abilities in childhood, or rather explained by more general cognitive abilities.Methods193 VP/VLBW and 217 healthy term comparison participants were studied prospectively from birth to adulthood as part of a geographically defined study in Bavaria (South Germany). Mathematic and general cognitive abilities were assessed at 8 years with standardized tests; wealth information was assessed at 26 years with a structured interview and summarized into a comprehensive index score. All scores were z-standardized.ResultsAt 8 years, VP/VLBW (n = 193, 52.3% male) had lower mathematic and general cognitive abilities than healthy term comparison children (n = 217, 47.0% male). At 26 years, VP/VLBW had accumulated significantly lower overall wealth than term born comparison adults (-0.57 (1.08) versus -0.01 (1.00), mean difference 0.56 [0.36-0.77], p < .001). Structural equation modeling confirmed that VP/VLBW birth (β = -.13, p = .022) and childhood IQ (β = .24, p < .001) both directly predicted adult wealth, but math did not (β = .05, p = .413). Analyses were controlled for small-for-gestational-age (SGA) birth, child sex, and family socioeconomic status.ConclusionThis longitudinal study from birth to adulthood shows that VP/VLBW survivors' general cognitive rather than specific mathematic problems explain their diminished life-course success. These findings are important in order to design effective interventions at school age that reduce the burden of prematurity for those individuals who were born at highest neonatal risk.

Dataset Information

Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities.

Publications

Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities.

Similar Datasets

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