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| 2. |
- Darki, Fahimeh, et al.
(författare)
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DCDC2 polymorphism is associated with left temporoparietal gray and white matter structures during development.
- 2014
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 34:43, s. 14455-62
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Tidskriftsartikel (refereegranskat)abstract
- Three genes, DYX1C1, DCDC2, and KIAA0319, have been previously associated with dyslexia, neuronal migration, and ciliary function. Three polymorphisms within these genes, rs3743204 (DYX1C1), rs793842 (DCDC2), and rs6935076 (KIAA0319) have also been linked to normal variability of left temporoparietal white matter volume connecting the middle temporal cortex to the angular and supramarginal gyri. Here, we assessed whether these polymorphisms are also related to the cortical thickness of the associated regions during childhood development using a longitudinal dataset of 76 randomly selected children and young adults who were scanned up to three times each, 2 years apart. rs793842 in DCDC2 was significantly associated with the thickness of left angular and supramarginal gyri as well as the left lateral occipital cortex. The cortex was significantly thicker for T-allele carriers, who also had lower white matter volume and lower reading comprehension scores. There was a negative correlation between white matter volume and cortical thickness, but only white matter volume predicted reading comprehension 2 years after scanning. These results show how normal variability in reading comprehension is related to gene, white matter volume, and cortical thickness in the inferior parietal lobe. Possibly, the variability of gray and white matter structures could both be related to the role of DCDC2 in ciliary function, which affects both neuronal migration and axonal outgrowth.
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| 3. |
- Darki, Fahimeh, et al.
(författare)
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Three dyslexia susceptibility genes, DYX1C1, DCDC2, and KIAA0319, affect temporo-parietal white matter structure.
- 2012
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 72:8, s. 671-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Volume and integrity of white matter correlate with reading ability, but the underlying factors contributing to this variability are unknown.METHODS: We investigated single nucleotide polymorphisms in three genes previously associated with dyslexia and implicated in neuronal migration (DYX1C1, DCDC2, KIAA0319) and white matter volume in a cohort of 76 children and young adults from the general population.RESULTS: We found that all three genes contained polymorphisms that were significantly associated with white matter volume in the left temporo-parietal region and that white matter volume influenced reading ability.CONCLUSIONS: The identified region contained white matter pathways connecting the middle temporal gyrus with the inferior parietal lobe. The finding links previous neuroimaging and genetic results and proposes a mechanism underlying variability in reading ability in both normal and impaired readers.
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| 4. |
- Dumontheil, Iroise, et al.
(författare)
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Influence of the COMT genotype on working memory and brain activity changes during development.
- 2011
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 70:3, s. 222-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Valine158Methionine (Val158Met) polymorphism of the COMT gene leads to lower enzymatic activity and higher dopamine availability in Met carriers. The Met allele is associated with better performance and reduced prefrontal cortex activation during working memory (WM) tasks in adults. Dopaminergic system changes during adolescence may lead to a reduction of basal dopamine levels, potentially affecting Met allele benefits during development.METHODS: We investigated the association of COMT genotype with behavioral (n = 322) and magnetic resonance imaging data (n = 81-84) collected during performance of a visuospatial WM task and potential changes in these effects during development (reflected in age × genotype interactions). Data were collected from a cross-sectional and longitudinal typically developing sample of 6- to 20-year-olds.RESULTS: Visuospatial WM capacity exhibited an age × genotype interaction, with a benefit of the Met allele emerging after 10 years of age. There was a parallel age × genotype interaction on WM-related activation in the right inferior frontal gyrus and intraparietal sulcus (IPS), with increases in activation with age in the Val/Val group only. Main effects of COMT genotype were also observed in the IPS, with greater gray matter volumes bilaterally and greater right IPS activation in the Val/Val group compared with the Met carriers.CONCLUSIONS: These results suggest that COMT genotype effects on WM brain activity and behavior are not static during development. The full developmental picture should be considered when trying to understand the impact of genetic polymorphisms on the mature cognition of healthy adult or psychiatric populations.
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| 5. |
- Scerri, Thomas S, et al.
(författare)
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The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure.
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- Independent studies have shown that candidate genes for dyslexia and specific language impairment (SLI) impact upon reading/language-specific traits in the general population. To further explore the effect of disorder-associated genes on cognitive functions, we investigated whether they play a role in broader cognitive traits. We tested a panel of dyslexia and SLI genetic risk factors for association with two measures of general cognitive abilities, or IQ, (verbal and non-verbal) in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N>5,000). Only the MRPL19/C2ORF3 locus showed statistically significant association (minimum P = 0.00009) which was further supported by independent replications following analysis in four other cohorts. In addition, a fifth independent sample showed association between the MRPL19/C2ORF3 locus and white matter structure in the posterior part of the corpus callosum and cingulum, connecting large parts of the cortex in the parietal, occipital and temporal lobes. These findings suggest that this locus, originally identified as being associated with dyslexia, is likely to harbour genetic variants associated with general cognitive abilities by influencing white matter structure in localised neuronal regions.
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| 6. |
- Söderqvist, Stina, et al.
(författare)
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Dopamine, working memory, and training induced plasticity : implications for developmental research.
- 2012
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Ingår i: Developmental Psychology. - : American Psychological Association (APA). - 0012-1649 .- 1939-0599. ; 48:3, s. 836-43
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive deficits and particularly deficits in working memory (WM) capacity are common features in neuropsychiatric disorders. Understanding the underlying mechanisms through which WM capacity can be improved is therefore of great importance. Several lines of research indicate that dopamine plays an important role not only in WM function but also for improving WM capacity. For example, pharmacological interventions acting on the dopaminergic system, such as methylphenidate, improve WM performance. In addition, behavioral interventions for improving WM performance in the form of intensive computerized training have recently been associated with changes in dopamine receptor density. These two different means of improving WM performance--pharmacological and behavioral--are thus associated with similar biological mechanisms in the brain involving dopaminergic systems. This article reviews some of the evidence for the role of dopamine in WM functioning, in particular concerning the link to WM development and cognitive plasticity. Novel data are presented showing that variation in the dopamine transporter gene (DAT1) influences improvements in WM and fluid intelligence in preschool-age children following cognitive training. Our results emphasize the importance of the role of dopamine in determining cognitive plasticity.
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| 7. |
- Söderqvist, Stina, et al.
(författare)
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Polymorphisms in the dopamine receptor 2 gene region influence improvements during working memory training in children and adolescents.
- 2014
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Ingår i: Journal of cognitive neuroscience. - : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 26:1, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- Studying the effects of cognitive training can lead to finding better treatments, but it can also be a tool for investigating factors important for brain plasticity and acquisition of cognitive skills. In this study, we investigated how single-nucleotide polymorphisms (SNPs) and ratings of intrinsic motivation were associated to interindividual differences in improvement during working memory training. The study included 256 children aged 7-19 years who were genotyped for 13 SNPs within or near eight candidate genes previously implicated in learning: COMT, SLC6A3 (DAT1), DRD4, DRD2, PPP1R1B (DARPP32), MAOA, LMX1A, and BDNF. Ratings on the intrinsic motivation inventory were also available for 156 of these children. All participants performed at least 20 sessions of working memory training, and performance during the training was logged and used as the outcome variable. We found that two SNPs, rs1800497 and rs2283265, located near and within the dopamine receptor 2 (DRD2) gene, respectively, were significantly associated with improvements during training (p < .003 and p < .0004, respectively). Scores from a questionnaire regarding intrinsic motivation did not correlate with training outcome. However, we observed both the main effect of genotype at those two loci as well as the interaction between genotypes and ratings of intrinsic motivation (perceived competence). Both SNPs have previously been shown to affect DRD2 receptor density primarily in the BG. Our results suggest that genetic variation is accounting for some interindividual differences in how children acquire cognitive skills and that part of this effect is also seen on intrinsic motivation. Moreover, they suggest that dopamine D2 transmission in the BG is a key factor for cognitive plasticity.
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| 8. |
- Söderqvist, Stina, et al.
(författare)
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The SNAP25 gene is linked to working memory capacity and maturation of the posterior cingulate cortex during childhood.
- 2010
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 68:12, s. 1120-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Working memory (WM) is the ability to retain task relevant information. This ability is important for a wide range of cognitive tasks, and WM deficits are a central cognitive impairment in neurodevelopment disorders such as attention-deficit/hyperactivity disorder (ADHD). Although WM capacity is known to be highly heritable, most genes involved remain unidentified.METHODS: Single nucleotide polymorphisms in genes previously associated with cognitive functions or ADHD were selected for genotyping. Associations of these with WM tasks were investigated in a community sample of 330 children and young adults. One single nucleotide polymorphisms was also investigated in an independent sample of 88 4-year-old children. Furthermore, association between brain structure and activity, as measured by magnetic resonance imaging techniques, and single nucleotide polymorphisms alleles were estimated in 88 participants.RESULTS: Genotype at rs363039, located in the gene coding for synaptosomal-associated protein, 25 kDa (SNAP25) was associated to WM capacity in both samples. Associations in the community sample were also found with measures of other cognitive functions. In addition, this polymorphism affected the gray matter and brain activity in the posterior cingulate cortex, an area included in the so-called default mode network previously correlated to regulation of attention and hypothesized to be implicated in ADHD.CONCLUSIONS: A novel gene-brain-behavior network was identified in which a genotype located in SNAP25 affects WM and has age-dependent effects on both brain structure and brain activity. Identifying such networks could be a key to better understanding cognitive development as well as some of its disorders.
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