scholarly journals Genetic markers of ADHD-related variations in intracranial volume

2017 ◽  
Author(s):  
Marieke Klein ◽  
Raymond K. Walters ◽  
Ditte Demontis ◽  
Jason L. Stein ◽  
Derrek P. Hibar ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Meta Analysis ◽  
Neurodevelopmental Disorder ◽  
Structure And Function ◽  
Intracranial Volume ◽  
Biological Mechanisms ◽  
Brain Volumes ◽  
Hyperactivity Disorder ◽  
Genetic Overlap ◽  
And Function

ABSTRACTAttention-Deficit/Hyperactivity Disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with a complex pathophysiology, where genetic risk is hypothesized to be mediated by alterations in structure and function of diverse brain networks. We tested one aspect of this hypothesis by investigating the genetic overlap between ADHD (n=55,374) and (mainly subcortical) brain volumes (n=11,221-24,704), using the largest publicly available studies. At the level of common variant genetic architecture, we discovered a significant negative genetic correlation between ADHD and intracranial volume (ICV). Meta-analysis of individual variants found significant loci associated with both ADHD risk and ICV; additional loci were identified for ADHD and amygdala, caudate nucleus, and putamen volumes. Gene-set analysis in the ADHD-ICV meta-analytic data showed significant association with variation in neurite outgrowth-related genes. In summary, our results suggest new hypotheses about biological mechanisms involved in ADHD etiology and highlight the need to study additional brain parameters.

scholarly journals Shared genetic background between children and adults with attention deficit/hyperactivity disorder

2019 ◽  
Author(s):  
Paula Rovira ◽  
Ditte Demontis ◽  
Cristina Sánchez-Mora ◽  
Tetyana Zayats ◽  
Marieke Klein ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Genetic Variants ◽  
Genetic Background ◽  
Genetic Architecture ◽  
Neurodevelopmental Disorder ◽  
Genome Wide Association Studies ◽  
Hyperactivity Disorder ◽  
Common Genetic Variants ◽  
Shared Genetic

AbstractAttention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.

Basic mechanisms and treatment planning/targets for attention-deficit/hyperactivity disorder

2020 ◽  
pp. 309-317
Author(s):  
Barbara Franke ◽  
Jan K. Buitelaar
Keyword(s):  
Treatment Options ◽  
Disease Onset ◽  
Genetic Research ◽  
Structure And Function ◽  
Reward Processing ◽  
Hyperactivity Disorder ◽  
Brain Structure And Function ◽  
Genetic Level ◽  
And Function ◽  
Different Levels

The mechanisms underlying ADHD are complex and can be defined at different levels. Cognitive deficits are often part of the disorder, including problems in executive functioning, reward processing, and timing deficits. Alterations have also been reported in brain structure and function in people with the disorder. ADHD is known to be a highly heritable, multifactorial disorder, in which genetic factors—often in combination with environmental factors—are risk factors for disease onset. Early research at the genetic level has implicated monoaminergic neurotransmission, following the serendipitous finding that methylphenidate, a dopamine and noradrenaline transport inhibitor, treats ADHD symptoms. The current models to explain brain malfunctioning in ADHD indeed centre around these monoamine systems. In addition to dopamine, noradrenaline, and (to a lesser extent) serotonin, also glutamate, histamine, and the nicotinic acetylcholinergic system seem to be involved in ADHD aetiology. In the coming years, genetic research is expected to uncover more of the mechanisms underlying ADHD, hopefully resulting in improved treatment options.

scholarly journals Electromyogram-Related Neuromuscular Electrical Stimulation for Restoring Wrist and Hand Movement in Poststroke Hemiplegia: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 33 (2) ◽  
pp. 96-111 ◽  
Author(s):  
Katia Monte-Silva ◽  
Daniele Piscitelli ◽  
Nahid Norouzi-Gheidari ◽  
Marc Aureli Pique Batalla ◽  
Philippe Archambault ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Electrical Stimulation ◽  
Meta Analysis ◽  
Neuromuscular Electrical Stimulation ◽  
Structure And Function ◽  
Motor Recovery ◽  
Body Structure ◽  
Short Term ◽  
And Function

Background. Clinical trials have demonstrated some benefits of electromyogram-triggered/controlled neuromuscular electrical stimulation (EMG-NMES) on motor recovery of upper limb (UL) function in patients with stroke. However, EMG-NMES use in clinical practice is limited due to a lack of evidence supporting its effectiveness. Objective. To perform a systematic review and meta-analysis to determine the effects of EMG-NMES on stroke UL recovery based on each of the International Classification of Functioning, Disability, and Health (ICF) domains. Methods. Database searches identified clinical trials comparing the effect of EMG-NMES versus no treatment or another treatment on stroke upper extremity motor recovery. A meta-analysis was done for outcomes at each ICF domain (Body Structure and Function, Activity and Participation) at posttest (short-term) and follow-up periods. Subgroup analyses were conducted based on stroke chronicity (acute/subacute, chronic phases). Sensitivity analysis was done by removing studies rated as poor or fair quality (PEDro score <6). Results. Twenty-six studies (782 patients) met the inclusion criteria. Fifty percent of them were considered to be of high quality. The meta-analysis showed that EMG-NMES has a robust short-term effect on improving UL motor impairment in the Body Structure and Function domain. No evidence was found in favor of EMG-NMES for the Activity and Participation domain. EMG-NMES had a stronger effect for each ICF domain in chronic (≥3 months) compared to acute/subacute phases. Conclusion. EMG-NMES is effective in the short term in improving UL impairment in individuals with chronic stroke.

Letter to the Editor: Exercise Interventions and Cardiovascular Health in Childhood Cancer: A Meta-Analysis

2020 ◽  
Vol 41 (09) ◽  
pp. 628-629 ◽  
Author(s):  
Paola Victória da Costa Ghignatti ◽  
Ricardo Pereira de Lima
Keyword(s):  
Childhood Cancer ◽  
Sports Medicine ◽  
Cardiovascular Health ◽  
Meta Analysis ◽  
Childhood Cancer Survivors ◽  
Structure And Function ◽  
Training Intervention ◽  
Exercise Interventions ◽  
Cardiac Structure And Function ◽  
And Function

Dear Editor,International Journal of Sports MedicineThe analysis of the study entitled “Exercise Interventions and Cardiovascular Health in Childhood Cancer: a Meta-Analysis” 1 was very interesting. The authors of this meta-analysis aimed to summarize the evidence on the effects of physical training intervention over three weeks on cardiovascular and cardiorespiratory outcomes in childhood cancer survivors (CCS). In addition, they addressed endpoints related not only to cardiac structure and function, but also to cardiorespiratory fitness.

scholarly journals Insights into the structure and function of HV1 from a meta-analysis of mutation studies

2016 ◽  
Vol 148 (2) ◽  
pp. 97-118 ◽  
Author(s):  
Thomas E. DeCoursey ◽  
Deri Morgan ◽  
Boris Musset ◽  
Vladimir V. Cherny
Keyword(s):  
Amino Acid ◽  
Ion Channel ◽  
Meta Analysis ◽  
Structure And Function ◽  
Proton Channel ◽  
Vast Array ◽  
Voltage Gated ◽  
Interspecies Differences ◽  
And Function ◽  
Sheer Number

The voltage-gated proton channel (HV1) is a widely distributed, proton-specific ion channel with unique properties. Since 2006, when genes for HV1 were identified, a vast array of mutations have been generated and characterized. Accessing this potentially useful resource is hindered, however, by the sheer number of mutations and interspecies differences in amino acid numbering. This review organizes all existing information in a logical manner to allow swift identification of studies that have characterized any particular mutation. Although much can be gained from this meta-analysis, important questions about the inner workings of HV1 await future revelation.

scholarly journals Structure and function of a neocortical synapse

2019 ◽  
Author(s):  
Simone Holler-Rickauer ◽  
German Köstinger ◽  
Kevan A.C. Martin ◽  
Gregor F.P. Schuhknecht ◽  
Ken J. Stratford
Keyword(s):  
Pyramidal Neurons ◽  
Structure And Function ◽  
Excitatory Postsynaptic Potential ◽  
Brain Volumes ◽  
C Elegans ◽  
Synaptic Release ◽  
Hippocampal Synapses ◽  
Large Brain ◽  
And Function ◽  
Whole Cell Recordings

Thirty-four years since the small nervous system of the nematode C. elegans was manually reconstructed in the electron microscope (EM)1, ‘high-throughput’ EM techniques now enable the dense reconstruction of neural circuits within increasingly large brain volumes at synaptic resolution2–6. As with C. elegans, however, a key limitation for inferring brain function from neuronal wiring diagrams is that it remains unknown how the structure of a synapse seen in EM relates to its physiological transmission strength. Here, we related structure and function of the same synapses to bridge this gap: we combined paired whole-cell recordings of synaptically connected pyramidal neurons in slices of mouse somatosensory cortex with correlated light microscopy and high-resolution EM of all putative synaptic contacts between the neurons. We discovered a linear relationship between synapse size (postsynaptic density area) and synapse strength (excitatory postsynaptic potential amplitude), which provides an experimental foundation for assigning the actual physiological weights to synaptic connections seen in the EM. Furthermore, quantal analysis revealed that the number of vesicle release sites exceeded the number of anatomical synapses formed by a connection by a factor of at least 2.6, which challenges the current understanding of synaptic release in neocortex and suggests that neocortical synapses operate with multivesicular release, like hippocampal synapses7–11. Thus, neocortical synapses are more complex computational devices and may modulate their strength more flexibly than previously thought, with the corollary that the canonical neocortical microcircuitry possesses significantly higher computational power than estimated by current models.

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