1. Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S, Barnhouse S, Lee W. {{Effect of a vitamin/mineral supplement on children and adults with autism}}. {BMC Pediatr};2011 (Dec 12);11(1):111.
ABSTRACT: BACKGROUND: Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited. METHOD: This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted. RESULTS: The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p=0.001), S-adenosylmethionine (SAM; +6%, p=0.003), reduced glutathione (+17%, p=0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p=0.002), nitrotyrosine (-29%, p=0.004), ATP (+25%, p=0.000001), NADH (+28%, p=0.0002), and NADPH (+30%, p=0.001). Most of these metabolic biomarkers improved to normal or near-normal levels. The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p=0.008), and on the subscores for Hyperactivity (p=0.003), Tantrumming (p=0.009), Overall (p=0.02), and Receptive Language (p=0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant. Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R2 = 0.61, p<0.0005) with the initial levels of biotin and vitamin K being the most significant (p<0.05); both biotin and vitamin K are made by beneficial intestinal flora. CONCLUSIONS: Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism. Trial registration number NCT01225198.
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2. Meyer KJ, Axelsen MS, Sheffield VC, Patil SR, Wassink TH. {{Germline mosaic transmission of a novel duplication of PXDN and MYT1L to two male half-siblings with autism}}. {Psychiatr Genet};2011 (Dec 12)
Autism is a neurodevelopmental disorder with a strong genetic component to susceptibility. In this study, we report the molecular characterization of an apparent de-novo 281 kb duplication of chromosome 2p25.3 in two male half-siblings with autism. The 2p25.3 duplication was first identified through a low-density microarray, validated with fluorescent in-situ hybridization, and duplication breakpoints were delineated using an Affymetrix 6.0 single-nucleotide polymorphism microarray. The fluorescent in-situ hybridization results validated the novel copy number variant and revealed the mother to be mosaic, with approximately 33% of her lymphoblast cells carrying the duplication. Therefore, the duplication was transmitted through the mechanism of germline mosaicism. In addition, duplication breakpoints were refined and showed that PXDN is fully duplicated, whereas seven exons of the terminal portion of the 25 exon gene MYT1L are within the duplicated region. MYT1L, a gene predominately expressed in the brain, has recently been linked with other neuropsychiatric illness such as schizophrenia and depression. Results from this study indicate that the 2p25.3 duplication disrupting PXDN and MYT1L is a potential autism-causing variant in the pedigree reported here and should receive further consideration as a candidate for autism.
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3. Seltzer MM, Barker ET, Greenberg JS, Hong J, Coe C, Almeida D. {{Differential sensitivity to life stress in FMR1 premutation carrier mothers of children with fragile X syndrome}}. {Health Psychol};2011 (Dec 12)
Objective: The premutation of the FMR1 gene (defined as between 55 and 200 CGG repeats) is estimated to affect 1 in 149 females and 1 in 643 males, and some people who carry the FMR1 premutation display signs of impairment. Method: This study focuses on 82 premutation carrier mothers (M age = 51.4 years; SD = 7.7) of adolescent and adult children with fragile X syndrome (FXS). A Gene x Environment interaction approach examined the ways in which the experience of negative life events interacts with genetic vulnerability to predict depressive symptoms, anxiety, and daily cortisol levels. Results: The associations of life events with all 3 dependent measures were associated with CGG repeat length but in a curvilinear manner. Mothers with midsize CGG repeats who experienced above-average numbers of negative life events in the previous year had more depressive symptoms and anxiety and had a blunted cortisol awakening response, as compared with those with higher or lower repeat lengths. However, mothers with midsize CGG repeats who experienced below-average numbers of negative life events in the previous year had the lowest levels of depressive symptoms and anxiety, and they exhibited the typical cortisol response to awakening, meeting the criteria for differential susceptibility. Conclusions: This research extends our understanding of the phenotypic effects of the expansion of the FMR1 gene, and it adds to the growing literature on the curvilinear relationship between CGG repeat length and mental and physical health. (PsycINFO Database Record (c) 2011 APA, all rights reserved).
