1. Alfawaz HA, Bhat RS, Al-Ayadhi L, El-Ansary AK. {{Protective and restorative potency of Vitamin D on persistent biochemical autistic features induced in propionic acid-intoxicated rat pups}}. {BMC Complement Altern Med};2014 (Oct 25);14(1):416.
BACKGROUND: Reducing exposure to toxic environmental agents is a critical area of intervention. Prenatal or postnatal exposure to certain chemicals has been documented to increase the risk of autism spectrum disorder. Propionic acid (PA) found in some foods and formed as a metabolic product of gut microbiota has been reported to mediate the effects of autism.Results from animal studies may help to identify environmental contaminants and drugs that produce or prevent neurotoxicity, and may thereby aid in the treatment of neurodevelopmental disorders such as autism. The present study investigated the protective and/or therapeutic effects of vitamin D against brain intoxication induced by propionic acid (PPA) in rats. METHODS: Twenty-eight young male Western Albino rats were enrolled in the present study. They were grouped into four equal groups of 7. The control group received only phosphate buffered saline; the oral buffered PPA-treated group received a neurotoxic dose of 250 mg/kg body weight/day for 3 days; and the Vitamin D-protected group received 1000 IU/kg/day of alpha, 25-dihydroxyvitamin D (3) (1, 25-VD) for two weeks, after which the rats were injected with PPA 250 mg/Kg body weight/day for 3 days. The fourth group received PPA 250 mg/Kg body weight/day for 3 days followed by alpha, 25-dihydroxyvitamin D (3) (1, 25-VD) for two weeks (Vitamin D therapeutic effect).Vitamin D and calcium were measured in the plasma of the four studied groups. Serotonin, interferon gamma (IFN-gamma), glutathione-s-transferase activity and DNA double helix breaks were assayed in the brain tissue of the rats for all groups. RESULTS: The obtained data showed that the PPA-treated group demonstrated higher plasma vitamin D levels compared to the control rats, together with multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), an increase in IFN-gamma and inhibition of glutathione-s-transferase activity as three biomarkers of brain dysfunction. Additionally, Comet DNA assays showed remarkably higher tail length, tail DNA % damage and tail moment as a neurotoxic effect of PPA. CONCLUSIONS: Vitamin D showed a greater protective than therapeutic effect on PPA-induced neurotoxicity in rats, as there was a remarkable amelioration of the impaired biochemically measured parameters representing neurochemical, inflammation, and detoxification processes.
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2. Curran EA, O’Neill SM, Cryan JF, Kenny LC, Dinan TG, Khashan AS, Kearney PM. {{Research Review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis}}. {J Child Psychol Psychiatry};2014 (Oct 27)
BACKGROUND: Given the growing prevalence of birth by Caesarean section (CS) worldwide, it is important to understand any long-term effects CS delivery may have on a child’s development. We assessed the impact of mode of delivery on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a systematic review of the literature in PubMed, Embase, CINAHL, PsycINFO and Web of Science up to 28 February 2014. No publication date, language, location or age restrictions were employed. RESULTS: Thirteen studies reported an adjusted estimate for CS-ASD, producing a pooled odds ratio (OR) of 1.23 (95% CI: 1.07, 1.40). Two studies reported an adjusted estimate for CS-ADHD, producing a pooled OR of 1.07 (95% CI: 0.86, 1.33). CONCLUSIONS: Delivery by CS is associated with a modest increased odds of ASD, and possibly ADHD, when compared to vaginal delivery. Although the effect may be due to residual confounding, the current and accelerating rate of CS implies that even a small increase in the odds of disorders, such as ASD or ADHD, may have a large impact on the society as a whole. This warrants further investigation.
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3. de Bruin EI, Blom R, Smit FM, van Steensel FJ, Bogels SM. {{MYmind: Mindfulness training for Youngsters with autism spectrum disorders and their parents}}. {Autism};2014 (Oct 27)
BACKGROUND: Despite the dramatic increase in autism spectrum disorder in youth and the extremely high costs, hardly any evidence-based interventions are available. The aim of this study is to examine the effects of mindfulness training for adolescents with autism spectrum disorder, combined with Mindful Parenting training. METHOD: A total of 23 adolescents with autism spectrum disorder, referred to a mental health clinic, received nine weekly sessions of mindfulness training in group format. Their parents (18 mothers, 11 fathers) participated in parallel Mindful Parenting training. A pre-test, post-test, and 9-week follow-up design was used. Data were analyzed using multi-level analyses. RESULTS: Attendance rate was 88% for adolescents and fathers and 86% for mothers. Adolescents reported an increase in quality of life and a decrease in rumination, but no changes in worry, autism spectrum disorder core symptoms, or mindful awareness. Although parents reported no change in adolescent’s autism spectrum disorder core symptoms, they reported improved social responsiveness, social communication, social cognition, preoccupations, and social motivation. About themselves, parents reported improvement in general as well as in parental mindfulness. They reported improved competence in parenting, overall parenting styles, more specifically a less lax, verbose parenting style, and an increased quality of life. DISCUSSION: Mindfulness training for adolescents with autism spectrum disorder combined with Mindful Parenting is feasible. Although the sample size was small and no control group was included, the first outcomes of this innovative training are positive.
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4. Hardan AY, Gengoux GW, Berquist KL, Libove RA, Ardel CM, Phillips J, Frazier TW, Minjarez MB. {{A randomized controlled trial of Pivotal Response Treatment Group for parents of children with autism}}. {J Child Psychol Psychiatry};2014 (Oct 27)
BACKGROUND: With rates of autism diagnosis continuing to rise, there is an urgent need for effective and efficient service delivery models. Pivotal Response Treatment (PRT) is considered an established treatment for autism spectrum disorder (ASD); however, there have been few well-controlled studies with adequate sample size. The aim of this study was to conduct a randomized controlled trial to evaluate PRT parent training group (PRTG) for targeting language deficits in young children with ASD. METHODS: Fifty-three children with autism and significant language delay between 2 and 6 years old were randomized to PRTG (N = 27) or psychoeducation group (PEG; N = 26) for 12 weeks. The PRTG taught parents behavioral techniques to facilitate language development. The PEG taught general information about ASD (clinical trial NCT01881750; http://www.clinicaltrials.gov). RESULTS: Analysis of child utterances during the structured laboratory observation (primary outcome) indicated that, compared with children in the PEG, children in the PRTG demonstrated greater improvement in frequency of utterances (F(2, 43) = 3.53, p = .038, d = 0.42). Results indicated that parents were able to learn PRT in a group format, as the majority of parents in the PRTG (84%) met fidelity of implementation criteria after 12 weeks. Children also demonstrated greater improvement in adaptive communication skills (Vineland-II) following PRTG and baseline Mullen visual reception scores predicted treatment response to PRTG. CONCLUSIONS: This is the first randomized controlled trial of group-delivered PRT and one of the largest experimental investigations of the PRT model to date. The findings suggest that specific instruction in PRT results in greater skill acquisition for both parents and children, especially in functional and adaptive communication skills. Further research in PRT is warranted to replicate the observed results and address other core ASD symptoms.
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5. Jyonouchi H, Geng L, Davidow AL. {{Cytokine profiles by peripheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: an inflammatory subtype?}}. {J Neuroinflammation};2014 (Oct 27);11(1):187.
BackgroundSome children with autism spectrum disorders (ASD) are characterized by fluctuating behavioral symptoms following immune insults, persistent gastrointestinal (GI) symptoms, and a lack of response to the first-line intervention measures. These children have been categorized as the ASD-inflammatory subtype (ASD-IS) for this study. We reported a high prevalence of non-IgE mediated food allergy (NFA) in young ASD children before, but not all ASD/NFA children reveal such clinical features of ASD-IS. This study addressed whether behavioral changes of ASD-IS are associated with innate immune abnormalities manifested in isolated peripheral blood (PB) monocytes (Mo), major innate immune cells in the PB.MethodsThis study includes three groups of ASD subjects (ASD-IS subjects (N =24), ASD controls with a history of NFA (ASD/NFA (N =20), and ASD/non-NFA controls (N =20)) and three groups of non-ASD controls (non-ASD/NFA subjects (N =16), those diagnosed with pediatric acute onset-neuropsychiatric syndrome (PANS, N =18), and normal controls without NFA or PANS (N =16)). Functions of purified PB Mo were assessed by measuring the production of inflammatory and counter-regulatory cytokines with or without stimuli of innate immunity (lipopolysaccharide (LPS), zymosan, CL097, and candida heat extracts as a source of ss-lactam). In ASD-IS and PANS subjects, these assays were done in the state of behavioral exacerbation (`flare inverted question mark) and in the stable (`non-flare inverted question mark) condition. ASD-IS children in the `flare inverted question mark state revealed worsening irritability, lethargy and hyperactivity.Results`Flare inverted question mark ASD-IS PB Mo produced higher amounts of inflammatory cytokines (IL-1ss and IL-6) without stimuli than `non-flare inverted question mark ASD-IS cells. With zymosan, `flare inverted question mark ASD-IS cells produced more IL-1ss than most control cells, despite spontaneous production of large amounts of IL-1ss. Moreover, `flare inverted question mark ASD-IS Mo produced less IL-10, a counterregulatory cytokine, in response to stimuli than `non-flare inverted question mark cells or other control cells. These changes were not observed in PANS cells.ConclusionsWe observed an imbalance in the production of inflammatory (IL-1ss and IL-6) and counterregulatory (IL-10) cytokines by `flare inverted question mark ASD-IS monocytes, which may indicate an association between intrinsic abnormalities of PB Mo and changes in behavioral symptoms in the ASD-IS subjects.
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6. Zeglam AM, Al-Ogab MF, Al-Shaftery T. {{MRI or not to MRI! Should brain MRI be a routine investigation in children with autistic spectrum disorders?}}. {Acta Neurol Belg};2014 (Oct 26)
To evaluate the routine usage of Magnetic Resonance Imaging (MRI) of brain and estimate the prevalence of brain abnormalities in children presenting to the Neurodevelopment Clinic of Al-Khadra Hospital (NDC-KH), Tripoli, Libya with autistic spectrum disorders (ASD). The records of all children with ASD presented to NDC-KH over 4-year period (from January 2009 to December 2012) were reviewed. All MRIs were acquired with a 1.5-T Philips (3-D T1, T2, FLAIR coronal and axial sequences). MRIs were reported to be normal, abnormal or no significant abnormalities by a consultant neuroradiologist. One thousand and seventy-five children were included in the study. Seven hundred and eighty-two children (72.7 %) had an MRI brain of whom 555 (71 %) were boys. 26 children (24 males and 2 females) (3.3 %) demonstrated MRI abnormalities (8 leukodystrophic changes, 4 periventricular leukomalacia, 3 brain atrophy, 2 tuberous sclerosis, 2 vascular changes, 1 pineoblastoma, 1 cerebellar angioma, 1 cerebellar hypoplasia, 3 agenesis of corpus callosum, 1 neuro-epithelial cyst). An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in children with autism. These results could contribute to further research into the pathogenesis of autistic spectrum disorder.
