| 1. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 2. |
- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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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.
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| 3. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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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.
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| 4. |
- Kaufmann, Tobias, et al.
(författare)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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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.
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| 5. |
- Hoekstra, P J, et al.
(författare)
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Emotional development in children with tics: a longitudinal population-based study.
- 2013
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Ingår i: European child & adolescent psychiatry. - : Springer Science and Business Media LLC. - 1435-165X .- 1018-8827. ; 22:3, s. 185-192
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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.
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| 6. |
- Heiervang, Einar, et al.
(författare)
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Psychiatric disorders in Norwegian 8- to 10-year-olds: an epidemiological survey of prevalence, risk factors, and service use.
- 2007
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 46:4, s. 438-447
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The Bergen Child Study is a longitudinal study of child mental health from the city of Bergen, Norway. We present methods and results from the first wave of the study, focusing on prevalence of disorders, associations with risk factors, and the use of services. METHOD: The target population included all 9,430 children attending grades 2 to 4 in Bergen schools during the academic year 2002/2003. The main screening instrument was the Strengths and Difficulties Questionnaire, whereas diagnoses were based on the Development and Well-Being Assessment. Information about child and family risk factors and service use was also obtained in this second stage. RESULTS: In the first phase, the teacher Strengths and Difficulties Questionnaire was obtained for 9,155 (97%) of the target children and the matching parent Strengths and Difficulties Questionnaire for 6,297 (67%); 1,011 children (11%) were assessed with the Development and Well-Being Assessment in the second phase. The weighted prevalence for any DSM-IV psychiatric disorder was 7.0% (95% confidence interval 5.6%-8.5%). Disorders were associated with age, gender, learning difficulties, family type, and poverty. Although 75% of children with attention-deficit/hyperactivity disorder had been in contact with specialist mental health services, this was true for only 13% of those with pure emotional disorders. CONCLUSIONS: The overall prevalence of psychiatric disorders in children is relatively low in this Norwegian sample, when assessed with the Development and Well-Being Assessment. Children with emotional disorders have limited access to specialist services.
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| 7. |
- Ekornas, Belinda, et al.
(författare)
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Anxiety disorders in 8-11-year-old children: Motor skill performance and self-perception of competence
- 2010
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Ingår i: SCANDINAVIAN JOURNAL OF PSYCHOLOGY. - : Blackwell Publishing Ltd. - 0036-5564 .- 1467-9450. ; 51:3, s. 271-277
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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.
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| 8. |
- Ekornas, Belinda, et al.
(författare)
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PRIMARY SCHOOL CHILDRENS PEER RELATIONSHIPS: DISCREPANCIES IN SELF-PERCEIVED SOCIAL ACCEPTANCE IN CHILDREN WITH EMOTIONAL OR BEHAVIORAL DISORDERS
- 2011
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Ingår i: Journal of Social and Clinical Psychology. - : Guilford Press. - 0736-7236 .- 1943-2771. ; 30:6, s. 570-582
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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.
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| 9. |
- Hysing, Mari, et al.
(författare)
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Chronic physical illness and mental health in children. Results from a large-scale population study.
- 2007
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Ingår i: Journal of Child Psychology and Psychiatry, and Allied Disciplines. - : Wiley. - 0021-9630 .- 1469-7610. ; 48:8, s. 785-792
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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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| 10. |
- Hysing, Mari, et al.
(författare)
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Emotional and behavioural problems in subgroups of children with chronic illness: results from a large-scale population study.
- 2009
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Ingår i: Child: Care, Health and Development. - : Wiley. - 0305-1862 .- 1365-2214. ; 35:4, s. 527-533
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Children with chronic illness are known to have an increased risk of emotional and behavioural problems. In the present population-based study children with asthma, neurological disorders and other chronic illnesses were compared with children without chronic illnesses to assess differences in psychological presentation across illness groups. METHODS: A total of 537 children with parent-reported chronic illness in the Bergen Child Study were categorized into three groups: asthma, neurological disorders and other chronic illnesses. Emotional and behavioural problems were assessed by the Strengths and Difficulties Questionnaire. RESULTS: All three illness groups had an increased rate of emotional and behavioural problems, as well as increased probability of a psychiatric disorder compared with children without a chronic illness. Most children with asthma and other chronic illnesses did not have emotional and behavioural problems, and effect sizes were small in both groups. In children with neurological disorders the effect sizes ranged from moderate to large, with emotional problems, inattention hyperactivity and peer problems being the most frequent problems. CONCLUSIONS: The increased rate of emotional and behavioural problems in children with chronic illness, especially neurological disorders, emphasizes the importance of early detection of mental health problems in these children.
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