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Sökning: WFRF:(Lundervold Astri J.)

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  • van der Meer, Dennis, et al. (författare)
  • Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
  • 2020
  • Ingår i: JAMA psychiatry. - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
  • Davies, Gail, et al. (författare)
  • Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
  • 2018
  • Ingår i: Nature Communications. - Nature Publishing Group. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
  • Sonderby, Ida E., et al. (författare)
  • Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
  • 2020
  • Ingår i: Molecular Psychiatry. - Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
  • Tidskriftsartikel (refereegranskat)abstract
    • Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
  • Kaufmann, Tobias, et al. (författare)
  • Common brain disorders are associated with heritable patterns of apparent aging of the brain
  • 2019
  • Ingår i: Nature Neuroscience. - Nature Publishing Group. - 1097-6256. ; 22:10, s. 1617-
  • Tidskriftsartikel (refereegranskat)abstract
    • Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
  • van der Meer, Dennis, et al. (författare)
  • Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes
  • 2018
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578.
  • Tidskriftsartikel (refereegranskat)abstract
    • The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.
  • Ekornas, Belinda, et al. (författare)
  • 2011
  • Ingår i: Journal of Social and Clinical Psychology. - Guilford Press. - 0736-7236. ; 30:6, s. 570-582
  • Tidskriftsartikel (refereegranskat)abstract
    • This population-based study investigated self-perception of social acceptance in children with emotional or behavioral disorders, and whether their perceptions were in line with parent/teacher reports of peer relationship problems. Children with behavioral disorders (n = 145) emotional disorders (n = 118), and a comparison group (n = 4,344) were selected from an 11-13-years-old population (n = 5073). Children with emotional disorders reported poorer social acceptance than children with behavioral disorders, also when adjusted for parent/teacher ratings of peer problems, confirming the negative self-perception reported in previous clinical studies. Self-perceptions of children with behavioral disorders were lower than in the comparison group and not inflated according to parent/teacher reports. The results emphasize the importance of peer-relations in both disorder groups.
  • Hoekstra, P J, et al. (författare)
  • Emotional development in children with tics: a longitudinal population-based study.
  • 2013
  • Ingår i: European child & adolescent psychiatry. - 1435-165X. ; 22:3, s. 185-192
  • Tidskriftsartikel (refereegranskat)abstract
    • Children with tics often experience accompanying problems that may have more impact on their well being and quality of life than the tics themselves. The present study investigates characteristics and the course of associated problems. In a population-based follow-up study, we investigated the developmental trajectory of children with and without tics when they were 7-9 years old. Parents and teachers completed the Strengths and Difficulties Questionnaire (SDQ) when the children were 7-9 years (wave 1) and 4 years later (wave 2). Using strict criteria, we identified 38 children with tics in the cohort of 4,025 children (0.94 % of the total cohort) with a preponderance of boys (78.9 %). 22 children (57.9 %) in the group with tics had only motor tics, and 16 (42.1 %) had both motor and vocal tics. Children with tics had significantly higher parent- and teacher-rated SDQ total difficulty scores and subscale scores in both waves. Children with tics experienced an increase in emotional problems and in peer problems between the first and the second wave. This study in a general population indicates that the presence of tics is associated with a range of internalizing and externalizing difficulties, as well as problems in peer relationships. Moreover, our study indicates that emotional and peer problems tend to increase over time in the group of children with tics.
  • Athanasiu, Lavinia, et al. (författare)
  • A genetic association study of CSMD1 and CSMD2 with cognitive function
  • 2017
  • Ingår i: Brain, behavior, and immunity. - 0889-1591. ; 61, s. 209-216
  • Tidskriftsartikel (refereegranskat)abstract
    • The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.
  • Ekornas, Belinda, et al. (författare)
  • Anxiety disorders in 8-11-year-old children: Motor skill performance and self-perception of competence
  • 2010
  • Ingår i: SCANDINAVIAN JOURNAL OF PSYCHOLOGY. - Blackwell Publishing Ltd. - 0036-5564. ; 51:3, s. 271-277
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates motor skill performance and self-perceived competence in children with anxiety disorders compared with children without psychiatric disorders. Motor skills and self-perception were assessed in 329 children aged 8 to 11 years, from the Bergen Child Study. The Kiddie-SADS PL diagnostic interview was employed to define a group of children with an anxiety disorder without comorbid diagnosis, and a control group (no diagnosis) matched according to gender, age, and full-scale IQ. Children in the anxiety disorder group displayed impaired motor skills and poor self-perceived peer acceptance and physical competence compared with the control group. Two-thirds of the anxious boys scored on the Motor Assessment Battery for Children (MABC) as having motor problems. The present study demonstrated impaired motor skills in boys with "pure" anxiety disorders. Anxious children also perceived themselves as being less accepted by peers and less competent in physical activities compared with children in the control group.
  • Hysing, Mari, et al. (författare)
  • Chronic physical illness and mental health in children. Results from a large-scale population study.
  • 2007
  • Ingår i: Journal of Child Psychology and Psychiatry, and Allied Disciplines. - 0021-9630. ; 48:8, s. 785-792
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aim of the present study was to evaluate the sensitivity and specificity of the Strengths and Difficulties Questionnaire (SDQ) in detecting emotional and behavioural problems among children with chronic illness (CI). METHODS: Parents and teachers of a population of primary school children in Norway (n = 9430) completed a questionnaire including the SDQ, and a question about chronic illness. A total of 74% (n = 7007) of the parents participated. A sub-sample (n = 1040) was given a psychiatric diagnostic evaluation according to the Development and Well-Being Assessment (DAWBA). RESULTS: According to parent reports, 537 (8%) children had a CI. The SDQ revealed an increased risk of emotional and behavioural problems in children with CI as compared with non-CI peers, both among boys (OR = 2.10 CI 95% 1.56-2.83) and girls (OR = 2.11 CI 95% 1.49-2.99). Children with CI also showed an increased risk of psychiatric disorder as assessed by the DAWBA (OR = 1.70 CI 95% 1.04-2.85). Both the sensitivity and specificity of the SDQ in predicting a psychiatric diagnosis were high, even when only information from parents was included. CONCLUSION: Children with CI in the general population are at increased risk of behavioural and emotional problems and psychiatric disorders. Given its high sensitivity and specificity the SDQ might work well as a screening instrument for behaviour/emotional problems and psychiatric disorder in children with CI.
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