Aggression in Low Functioning Children and Adolescents with Autistic Disorder

BACKGROUND: Parents, caregivers and mental health professionals have often reported violence and aggression in children or adolescents with autistic disorder. However, most of these observations derived from anecdotal reports, and studies on frequency and characterization of aggression in autism remain limited. Our objective was to better characterize and understand the different types of aggressive behaviors displayed by a large group of individuals with autism in different observational situations. METHODOLOGY/FINDINGS: The study was conducted on 74 children and adolescents with autism and 115 typically developing control individuals matched for sex, age and pubertal stage. Other-Injurious Behaviors (OIB) were assessed in three observational situations (parents at home, two caregivers at day-care, a nurse and a child psychiatrist during blood drawing) using validated scales. The frequency of OIB was significantly higher in individuals with autism compared to typically developing control individuals during the blood drawing (23% vs. 0%, P<0 .01). The parents observed significantly less OIB in their children than caregivers (34% vs. 58%, P<0.05). In addition, the most frequent concurrent behaviors occurring just before the appearance of OIB in individuals with autism were anxiety-related behaviors and excitation according to the parental as well as the caregiver observation. CONCLUSIONS/SIGNIFICANCE: The results suggest that in a stressful situation, such as the blood drawing, individuals with autism release their stress through behaviors such as OIB, whereas typically developing individuals regulate and express their stress through cognitive skills such as mental coping strategies, symbolization skills with representation and anticipation of the stressful situation, social interaction and verbal or non-verbal communication. The findings underline also the key role of the environment in assessing OIB and developing therapeutic perspectives, with an individual who modulates his/her behavior according to the environment, and an environment that perceives this behavior and reacts to it with different tolerance thresholds according to the observers

Modulation of Brain β-Endorphin Concentration by the Specific Part of the Y Chromosome in Mice

International audienceBackground: Several studies in animal models suggest a possible effect of the specific part of the Y-chromosome (Y NPAR) on brain opioid, and more specifically on brain b-endorphin (BE). In humans, male prevalence is found in autistic disorder in which observation of abnormal peripheral or central BE levels are also reported. This suggests gender differences in BE associated with genetic factors and more precisely with Y NPAR. Methodology/Principal Findings: Brain BE levels and plasma testosterone concentrations were measured in two highly inbred strains of mice, NZB/BlNJ (N) and CBA/HGnc (H), and their consomic strains for the Y NPAR. An indirect effect of the Y NPAR on brain BE level via plasma testosterone was also tested by studying the correlation between brain BE concentration and plasma testosterone concentration in eleven highly inbred strains. There was a significant and major effect (P,0.0001) of the Y NPAR in interaction with the genetic background on brain BE levels. Effect size calculated using Cohen's procedure was large (56% of the total variance). The variations of BE levels were not correlated with plasma testosterone which was also dependent of the Y NPAR. Conclusions/Significance: The contribution of Y NPAR on brain BE concentration in interaction with the genetic background is the first demonstration of Y-chromosome mediated control of brain opioid. Given that none of the genes encompassed by the Y NPAR encodes for BE or its precursor, our results suggest a contribution of the sex-determining region (Sry, carried by Y NPAR) to brain BE concentration. Indeed, the transcription of the Melanocortin 2 receptor gene (Mc2R gene, identified as the proopiomelanocortin receptor gene) depends on the presence of Sry and BE is derived directly from proopiomelanocortin. The results shed light on the sex dependent differences in brain functioning and the role of Sry in the BE system might be related to the higher frequency of autistic disorder in males

Combined transcriptomic-(1)H NMR metabonomic study reveals yhat monoethylhexyl phthalate stimulates adipogenesis and glyceroneogenesis in human adipocytes

Adipose tissue is a major storage site for lipophilic environmental contaminants. The environmental metabolic disruptor hypothesis postulates that some pollutants can promote obesity or metabolic disorders by activating nuclear receptors involved in the control of energetic homeostasis. In this context, monoethylhexyl phthalate (MEHP) is of particular concern since it was shown to activate the peroxisome proliferator-activated receptor γ (PPARγ) in 3T3-L1 murine preadipocytes. In the present work, we used an untargeted, combined transcriptomic-(1)H NMR-based metabonomic approach to describe the overall effect of MEHP on primary cultures of human subcutaneous adipocytes differentiated in vitro. MEHP stimulated rapidly and selectively the expression of genes involved in glyceroneogenesis, enhanced the expression of the cytosolic phosphoenolpyruvate carboxykinase, and reduced fatty acid release. These results demonstrate that MEHP increased glyceroneogenesis and fatty acid reesterification in human adipocytes. A longer treatment with MEHP induced the expression of genes involved in triglycerides uptake, synthesis, and storage; decreased intracellular lactate, glutamine, and other amino acids; increased aspartate and NAD, and resulted in a global increase in triglycerides. Altogether, these results indicate that MEHP promoted the differentiation of human preadipocytes to adipocytes. These mechanisms might contribute to the suspected obesogenic effect of MEHP

Adipocyte ATP-binding cassette G1 promotes triglyceride storage, fat mass growth, and human obesity

The role of ATP-binding Cassette G1 (ABCG1) transporter in human pathophysiology is still largely unknown. Indeed, beyond its role in mediating free cholesterol efflux to HDL, ABCG1 transporter equally promotes lipid accumulation in a triglyceride (TG)-rich environment through regulation of the bioavailability of Lipoprotein Lipase (LPL).As both ABCG1 and LPL are expressed in adipose tissue, we hypothesize that ABCG1 is implicated in adipocyte TG storage and could be then a major actor in adipose tissue fat accumulation.Silencing of Abcg1 expression by RNAi in 3T3-L1 preadipocytes compromised LPL-dependent TG accumulation during initial phase of differentiation. Generation of stable Abcg1 Knockdown 3T3-L1 adipocytes revealed that Abcg1 deficiency reduces TG storage and diminishes lipid droplet size through inhibition of Pparγ expression. Strikingly, local inhibition of adipocyte Abcg1 in adipose tissue from mice fed a high fat diet led to a rapid decrease of adiposity and weight gain. Analysis of two frequent ABCG1 SNPs (rs1893590 (A/C) and rs1378577 (T/G)) in morbidly obese individuals indicated that elevated ABCG1 expression in adipose tissue was associated with an increased PPARγ expression and adiposity concomitant to an increased fat mass and BMI (haplotype AT&gt;GC). The critical role of ABCG1 regarding obesity was further confirmed in independent populations of severe obese and diabetic obese individuals.For the first time, this study identifies a major role of adipocyte ABCG1 in adiposity and fat mass growth and suggests that adipose ABCG1 might represent a potential therapeutic target in obesity

Elevated Expression of Osteopontin May Be Related to Adipose Tissue Macrophage Accumulation and Liver Steatosis in Morbid Obesity

OBJECTIVE—Osteopontin (OPN) plays an important role in the development of insulin resistance and liver complications in dietary murine models. We aimed to determine the expression pattern of OPN and its receptor CD44 in obese patients and mice according to insulin resistance and liver steatosis

Adrenal suppression: A practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy

Inhaled corticosteroids (ICSs) are the most effective anti-inflammatory agents available for the treatment of asthma and represent the mainstay of therapy for most patients with the disease. Although these medications are considered safe at low-to-moderate doses, safety concerns with prolonged use of high ICS doses remain; among these concerns is the risk of adrenal suppression (AS). AS is a condition characterized by the inability to produce adequate amounts of the glucocorticoid, cortisol, which is critical during periods of physiological stress. It is a proven, yet under-recognized, complication of most forms of glucocorticoid therapy that can persist for up to 1 year after cessation of corticosteroid treatment. If left unnoticed, AS can lead to significant morbidity and even mortality. More than 60 recent cases of AS have been described in the literature and almost all cases have involved children being treated with ≥500 μg/day of fluticasone

Effect of Antihypertensive Therapy with Alpha Methyldopa on Levels of Angiogenic Factors in Pregnancies with Hypertensive Disorders

Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy

Marrow angiogenesis-associated factors as prognostic biomarkers in patients with acute myelogenous leukaemia

Bone marrow (BM) neoangiogenesis plays an important role in acute myelogenous leukaemia (AML), and depends on the interplay of members of the vascular endothelial growth factor (VEGF) and angiopoietin (Ang) families. We determined the marrow levels of seven molecules associated with angiogenesis in 52 AML patients before chemotherapy and 20 healthy controls: VEGF-A, VEGF/PlGF, VEGF-C, VEGF-D, Ang-1, Ang-2, and Tie-2. All the molecules were quantified using enzyme-linked immunosorbent assay (ELISA). Comparing to normal controls, the marrow levels of VEGF/PlGF, Ang-2, and Tie-2 were significantly higher, and those of VEGF-C and Ang-1 were significantly lower in the AML patients (P<0.001). A total of 31 patients were further subjected to survival analysis. Patients with lower Tie-2 (<26 ng ml−1) and Ang-2 levels (<4500 pg ml−1) displayed a survival advantage (P=0.037 and 0.042, respectively), same as patients with higher VEGF/PlGF (⩾1 pg ml−1) and VEGF-D levels (⩾350 pg ml−1) (P=0.020 and 0.016, respectively). An angio-index ((Ang-2 × Tie-2)/(VEGF/PlGF × VEGF-D)) was established and multivariate Cox regression analysis revealed that patients with higher angio-index values (⩾50) displayed poor prognosis (hazard ratio 5.91, 95% confidence interval 1.99–17.56; P=0.001). The angio-index is closely associated with the clinical outcome of AML patients and may be valuable in disease prognosis