Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function

Fliers, Ellen A.; Vásquez, Alejandro Arias; Poelmans, Geert; Rommelse, Nanda; Altink, Marieke E.; Buschgens, Cathelijne J. M.; Asherson, Philip; Banaschewski, Tobias; Ebstein, Richard P.; Gill, Michael; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A.; Sonuga‐Barke, Edmund; Steinhausen, Hans-Christoph; Faraone, Stephen V.; Buitelaar, Jan K.; Franke, Barbara

doi:10.3109/15622975.2011.560279

Cited by 37 publications

(27 citation statements)

References 58 publications

(16 reference statements)

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“…In light of these findings, one might ask if muscle release problems are involved in gross movements such as walking and running as well as in fine motor skills such as handwriting. Fliers et al [78] found an association between motor problems in ADHD and genes involved in muscles function.…”

Section: Discussionmentioning

confidence: 99%

Motor regulation problems and pain in adults diagnosed with ADHD

et al. 2013

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BackgroundMost children who are diagnosed with attention deficit-hyperactivity disorder (ADHD) have moderate-to-severe motor problems using the Motor Function Neurological Assessment battery (MFNU). The MFNU focuses on specific muscle adjustment problems associated with ADHD, especially motor inhibition problems and high muscle tone. Here we investigated whether adults with ADHD/hyperkinetic disorder (HKD) have similar motor problems. In our clinical experience, adults with ADHD often complain about back, shoulder, hip, and leg pain. We also investigate reported pain in adults with ADHD.MethodsTwenty-five adult outpatients diagnosed with ADHD/HKD who were responders to methylphenidate (MPH) were compared to 23 non-ADHD controls on 16 MFNU subtests and using a ‘total score’ (‘TS’) parameter. The MFNU test leader was blinded to group identity. The two groups were also compared using the Pain Drawing and Numerical Pain Rating Scale.ResultsThe adult ADHD group had significantly (p < .001) more motor problems (higher TS) than controls. On the muscle regulation subtests, 36–96% of the ADHD group showed ‘moderate’ to ‘severe’ problems compared to 13–52% of the control group, and 80% of the ADHD group reported widespread pain. Highly significant differences were found between the ADHD and control groups for the variables ‘pain level’ (p < .001) and ‘pain location’ (p < .001). Significant correlations were found between TS and ‘pain location’ and between TS and ‘pain level’.ConclusionsThese findings suggest that similar to children with ADHD, adults diagnosed with ADHD also have motor inhibition problems and heightened muscle tone. The presence of significantly higher pain levels and more widespread pain in the ADHD group compared to non-ADHD controls might indicate that pain is a long-term secondary effect of heightened muscle tone and restricted movement that can be demonstrated in children and adults by the MFNU battery.

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Section: Discussionmentioning

confidence: 99%

Motor regulation problems and pain in adults diagnosed with ADHD

et al. 2013

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“…The initial GWAS of ADHD [76][77][78][79][80][81][82][83][84][85][86] did not discover any DNA variants that achieved genome-wide significance, even when most of these samples were combined in metaanalysis having a sample size of 2064 trios (two parents and an ADHD child), 896 ADHD patients, and 2455 controls [87]. That study did find statistical significance for a group of candidate genes previously nominated by members of the International Multisite ADHD Genetics (IMAGE) project [88].…”

Section: Genome-wide Significant Common Variantsmentioning

confidence: 97%

Genetics of attention deficit hyperactivity disorder

2018

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Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD's high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD's heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD's heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.Attention deficit hyperactivity disorder (ADHD) is a childhood-onset condition with impairing symptoms of inattention, impulsivity, and hyperactivity. Decades of research have documented and replicated key facts about the disorder (for a review, see ref.[1]). It occurs in about 5% of children with little geographic or cross-cultural variation in prevalence and often co-occurs with other conditions, including mood, anxiety, conduct, learning, and substance use disorders. Longitudinal studies show that two-thirds of ADHD youth will continue to have impairing symptoms of ADHD in adulthood. People with ADHD are at risk for a wide range of functional impairments: school failure, peer rejection, injuries due to accidents, criminal behavior, occupational failure, divorce, suicide, and premature death. Although many details of ADHD's pathophysiology are unknown, neuropsychological and neuroimaging studies implicate brain circuits regulating executive functioning, reward processing, timing, and temporal information processing.This article reviews data about the role that genes play in the etiology of ADHD from two perspectives. Family, twin, and adoption studies provide a firm foundation for asserting that genes are involved in the etiology of ADHD. The view from molecular genetics provides a basis for understanding mechanisms whereby genes affect biological pathways that lead to ADHD. Family, twin and adoption studies of ADHDEvidence for heritability from family, adoption, and twin studies A study of 894 ADHD probands and 1135 of their siblings aged 5-17 years old found a ninefold increased risk of ADHD in siblings of ADHD probands compared with siblings of controls [2]. Adoption studies suggest that the familial factors of ADHD are attributable to genetic factors rather than shared environmental factors [3,4] with the most recent one reporting rates of ADHD to be greater among biological relatives of non-adopted ADHD children than adoptive relatives of adopted ADHD children. The adoptive relatives had a risk for ADHD like the risk in relatives of control childr...

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“…It is possible that RLS is co-morbid with ADHD or that they share a common DAergic deficit. Also, ADHD separately and ADHD together with RLS have been found to be associated with sleep disorders such as insomnia and a common genetic polymorphism [79-81]. In a recent study, 64% of children with ADHD were estimated to suffer from RLS judged by their nocturnal periodic limb movement [82].…”

Section: Methodsmentioning

confidence: 99%

The effects of Psychotropic drugs On Developing brain (ePOD) study: methods and design

et al. 2014

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BackgroundAnimal studies have shown that methylphenidate (MPH) and fluoxetine (FLX) have different effects on dopaminergic and serotonergic system in the developing brain compared to the developed brain. The effects of Psychotropic drugs On the Developing brain (ePOD) study is a combination of different approaches to determine whether there are related findings in humans.Methods/DesignAnimal studies were carried out to investigate age-related effects of psychotropic drugs and to validate new neuroimaging techniques. In addition, we set up two double-blind placebo controlled clinical trials with MPH in 50 boys (10–12 years) and 50 young men (23–40 years) suffering from ADHD (ePOD-MPH) and with FLX in 40 girls (12–14 years) and 40 young women (23–40 years) suffering from depression and anxiety disorders (ePOD-SSRI). Trial registration numbers are: Nederlands Trial Register NTR3103 and NTR2111. A cross-sectional cohort study on age-related effects of these psychotropic medications in patients who have been treated previously with MPH or FLX (ePOD-Pharmo) is also ongoing. The effects of psychotropic drugs on the developing brain are studied using neuroimaging techniques together with neuropsychological and psychiatric assessments of cognition, behavior and emotion. All assessments take place before, during (only in case of MPH) and after chronic treatment.DiscussionThe combined results of these approaches will provide new insight into the modulating effect of MPH and FLX on brain development.

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Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function

Cited by 37 publications

References 58 publications

Motor regulation problems and pain in adults diagnosed with ADHD

Motor regulation problems and pain in adults diagnosed with ADHD

Genetics of attention deficit hyperactivity disorder

The effects of Psychotropic drugs On Developing brain (ePOD) study: methods and design

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