Motor control in children with ADHD and non-affected siblings: deficits most pronounced using the left hand

Contains fulltext : 52261.pdf (publisher's version ) (Closed access)BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is strongly influenced by heritability. Identifying heritable vulnerability traits (endophenotypes) that mark a relatively high risk of developing the disorder can contribute to the identification of risk genes. A fruitful area for the search for such endophenotypes may be motor control in children with ADHD, since the disorder is frequently accompanied by motor problems. METHOD: The current study used a large sample of 350 children with ADHD, 195 non-affected siblings and 271 normal controls aged 5-19 years. Children were administered two computerised motor control tasks in which they had to trace a path between two circles (Tracking task) and follow a randomly moving target (Pursuit task). Both tasks were performed with both the right and the left hand. RESULTS: Children with ADHD were less precise and stable than controls. Non-affected siblings also deviated from controls, but only on the Tracking task. Group differences were modulated by the use of the right versus the left hand: no group differences emerged when the right hand was used, yet group differences did emerge when the left hand was used. Performance on both tasks was significantly familial. CONCLUSIONS: Imprecision and instability of movements in children with ADHD and in their non-affected siblings as measured by the Tracking task might be suitable endophenotypic candidates: these deficits are familially present in children having ADHD as well as in their non-affected siblings. Motor performance might be best assessed in children using their left hand, because motor control deficits are most pronounced using the left hand. This might relate to right hemispheric brain pathology in children with ADHD (and possibly in their non-affected siblings) that is related to the control of the left hand and/or relate to differential effects of daily life practice on both hands, which may be smaller on the left hand

Speed, Variability, and Timing of Motor Output in ADHD: Which Measures are Useful for Endophenotypic Research?

Attention-Deficit/Hyperactivity Disorder (ADHD) shares a genetic basis with motor coordination problems and probably motor timing problems. In line with this, comparable problems in motor timing should be observed in first degree relatives and might, therefore, form a suitable endophenotypic candidate. This hypothesis was investigated in 238 ADHD-families (545 children) and 147 control-families (271 children). A motor timing task was administered, in which children had to produce a 1,000 ms interval. In addition to this task, two basic motor tasks were administered to examine speed and variability of motor output, when no timing component was required. Results indicated that variability in motor timing is a useful endophenotypic candidate: It was clearly associated with ADHD, it was also present in non-affected siblings, and it correlated within families. Accuracy (under- versus over-production) in motor timing appeared less useful: Even though accuracy was associated with ADHD (probands and affected siblings had a tendency to under-produce the 1,000 ms interval compared to controls), non-affected siblings did not differ from controls and sibling correlations were only marginally significant. Slow and variable motor output without timing component also appears present in ADHD, but not in non-affected siblings, suggesting these deficits not to be related to a familial vulnerability for ADHD. Deficits in motor timing could not be explained by deficits already present in basic motor output without a timing component. This suggests abnormalities in motor timing were predominantly related to deficient motor timing processes and not to general deficient motor functioning. The finding that deficits in motor timing run in ADHD-families suggests this to be a fruitful domain for further exploration in relation to the genetic underpinnings of ADHD

Low circulating protein C levels are associated with lower leg ulcers in patients with diabetes. Biomed Res Int. 2013: 719570

Activated protein C (APC) promotes angiogenesis and reepithelialisation and accelerates healing of diabetic ulcers. e aim of this study was to determine the relationship between the incidence of lower leg ulcers and plasma levels of APC's precursor, protein C (PC), in diabetic patients. Patients with diabetes who had a lower leg ulcer(s) for >6 months ( ) were compared with age-, type of diabetes-, and sex-matched subjects with diabetes but without an ulcer ( , controls). Total PC was assessed using a routine PC colorimetric assay. ere was a signi�cantly ( ) lower level of plasma PC in patients with ulcers (103.3 ± 22.7, mean ± SD) compared with control ( 27 ± 4 ) subjects, when corrected for age and matched for gender and type of diabetes. �lcer type (neuropathic, ischaemic, or mixed) was not a signi�cant covariate for plasma PC levels ( ). ere was no correlation between PC levels and gender, type of diabetes, HbA c , or C-reactive protein in either group. In summary, decreased circulating PC levels are associated with, and may predispose to, lower leg ulceration in patients with diabetes

Low Circulating Protein C Levels Are Associated with Lower Leg Ulcers in Patients with Diabetes

Activated protein C (APC) promotes angiogenesis and reepithelialisation and accelerates healing of diabetic ulcers. The aim of this study was to determine the relationship between the incidence of lower leg ulcers and plasma levels of APC's precursor, protein C (PC), in diabetic patients. Patients with diabetes who had a lower leg ulcer(s) for >6 months (n=36) were compared with age-, type of diabetes-, and sex-matched subjects with diabetes but without an ulcer (n=36, controls). Total PC was assessed using a routine PC colorimetric assay. There was a significantly (P<0.001) lower level of plasma PC in patients with ulcers (103.3 ± 22.7, mean ± SD) compared with control (127.1±34.0) subjects, when corrected for age and matched for gender and type of diabetes. Ulcer type (neuropathic, ischaemic, or mixed) was not a significant covariate for plasma PC levels (P=0.35). There was no correlation between PC levels and gender, type of diabetes, HbA1c, or C-reactive protein in either group. In summary, decreased circulating PC levels are associated with, and may predispose to, lower leg ulceration in patients with diabetes

Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing

Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti-inflammatory mediator. Using cultured human cells, we show here that APC up-regulates the angiogenic promoters matrix metalloproteinase-2 in skin fibroblasts and umbilical vein endothelial cells, vascular endothelial growth factor in keratinocytes and fibroblasts, and monocyte chemoattractant protein-1 in fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the granulation/remodeling phases of wound healing by markedly stimulating angiogenesis as well as promoting reepithelialization. In a full-thickness rat skin-healing model, a single topical application of APC enhanced wound healing compared to saline control. APC-treated wounds had markedly more blood vessels on day 7 and a significantly lower infiltration of neutrophils at days 4 and 7. The broad spectrum matrix metallo-proteinas, GM6001, prevented the ability of APC to promote wound healing. In summary, our results show that APC promotes cutaneous wound healing via a complex mechanism involving stimulation of angiogenesis and inhibition of inflammation. These unique properties of APC make it an attractive therapeutic agent to promote the healing of chronic wounds. Copyright © 2005 by the Wound Healing Society