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- Buitelaar, J, et al.
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Toward Precision Medicine in ADHD
- 2022
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In: Frontiers in behavioral neuroscience. - : Frontiers Media SA. - 1662-5153. ; 16, s. 900981-
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Journal article (peer-reviewed)abstract
- Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.
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- Middeldorp, C. M., et al.
(author)
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A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts
- 2016
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In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567. ; 55:10
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Journal article (peer-reviewed)abstract
- Objective The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46× 10−6 and 2.66× 10−6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants. © 2016 American Academy of Child and Adolescent Psychiatry
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- Merwood, A., et al.
(author)
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Different heritabilities but shared etiological influences for parent, teacher and self-ratings of ADHD symptoms : an adolescent twin study
- 2013
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In: Psychological Medicine. - New York, USA : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 43:9, s. 1973-1984
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Journal article (peer-reviewed)abstract
- Background: Parent and teacher ratings of attention deficit hyperactivity disorder (ADHD) symptoms yield high estimates of heritability whereas self-ratings typically yield lower estimates. To understand why, the present study examined the etiological overlap between parent, teacher and self-ratings of ADHD symptoms in a population-based sample of 11-12-year-old twins. Method Participants were from the Twins Early Development Study (TEDS). ADHD symptoms were assessed using the Strengths and Difficulties Questionnaire (SDQ) hyperactivity scale completed by parents, teachers and children. Structural equation modeling was used to examine genetic and environmental contributions to phenotypic variance/covariance.Results: The broad-sense heritability of ADHD symptoms was 82% for parent ratings, 60% for teacher ratings and 48% for self-ratings. Post-hoc analyses revealed significantly higher heritability for same-teacher than different-teacher ratings of ADHD (76% v. 49%). A common pathway model best explained the relationship between different informant ratings, with common genetic influences accounting for 84% of the covariance between parent, teacher and self-rated ADHD symptoms. The remaining variance was explained by rater-specific genetic and non-shared environmental influences.Conclusions: Despite different heritabilities, there were shared genetic influences for parent, teacher and self-ratings of ADHD symptoms, indicating that different informants rated some of the same aspects of behavior. The low heritability estimated for self-ratings and different-teacher ratings may reflect increased measurement error when different informants rate each twin from a pair, and/or greater non-shared environmental influences. Future studies into the genetic influences on ADHD should incorporate informant data in addition to self-ratings to capture a pervasive, heritable component of ADHD symptomatology.
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- Stefanini, M., et al.
(author)
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Patient-reported outcomes and aesthetic evaluation of root coverage procedures: a 12-month follow-up of a randomized controlled clinical trial
- 2016
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In: Journal of Clinical Periodontology. - : Wiley. - 0303-6979. ; 43:12, s. 1132-1141
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Journal article (peer-reviewed)abstract
- Aim: To assess patient-reported outcome measures (PROMs), aesthetics and stability of root coverage procedures from a previous 6-month RCT after 1year. Material & Methods: Forty-five patients (90 recessions) had received a coronally advanced flap (CAF=control) only or a xenogeneic collagen matrix in addition (CAF+CMX=test). Visual analogue scales (VAS) and questionnaires were used for PROMs and the root coverage aesthetic score (RES) for professional aesthetic evaluations. Results: VAS scores (patient satisfaction) amounted to 8.58±1.86 (test) versus 8.38±2.46 (control). Six patients preferred CAF+CMX concerning surgical procedure and aesthetics, six preferred CAF and 29 were equally satisfied. RES was 7.85±2.42 for the test group versus 7.34±2.90 for the controls. Root coverage (RC) was 76.28% for test and 75.05% for control defects. The mean increase in keratinized tissue width was higher in test (from 1.97 to 3.02mm) than in controls (from 2.00 to 2.64 mm) (p=0.0413). Likewise, test sites showed more gain in gingival thickness (0.52mm) than control sites (0.27mm) (p=0.0023). Compared to 6months, clinical outcomes were stable. Conclusions: Results for PROMs, RES and RC did not significantly differ between treatment groups. Thickness and width of keratinized tissue were enhanced following CAF+CMX compared to CAF alone. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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