1. Delhey LM, Tippett M, Rose S, Bennuri SC, Slattery JC, Melnyk S, James SJ, Frye RE. {{Comparison of Treatment for Metabolic Disorders Associated with Autism:Reanalysis of Three Clinical Trials}}. {Front Neurosci}. 2018; 12: 19.
Autism spectrum disorder (ASD) affects about 1 in 45 individuals in the United States, yet effective treatments are yet to be defined. There is growing evidence that ASD is associated with abnormalities in several metabolic pathways, including the inter-connected folate, methylation and glutathione pathways. Several treatments that can therapeutically target these pathways have been tested in preliminary clinical trials. The combination of methylcobalamin (mB12) with low-dose folinic acid (LDFA) and sapropterin, a synthetic form of tetrahydrobiopterin (BH4) have been studied in open-label trials while high-dose folinic acid has been studied in a double-blind placebo controlled trial. All of these treatments have the potential to positively affect folate, methylation and glutathione pathways. Although the effect of mB12/LDFA and BH4 on methylation and glutathione metabolism have been examined in the open-label studies, these changes have not been compared to controls who received a placebo in order to account for the natural variation in the changes in these pathways. Furthermore, the recent study using high-dose folinic acid (HDFA) did not analyze the change in metabolism resulting from the treatment. Thus, we compared changes in methylation and glutathione metabolism and biomarkers of chronic oxidative stress as a result of these three treatments to individuals receiving placebo. In general, mB12/LDFA treatment had a significant effect on glutathione and cysteine metabolism with a medium effect size while BH4 had a significant effect on methylation and markers of chronic oxidative stress with a large effect size. HDFA treatment did not significantly influence biomarkers of methylation, glutathione or chronic oxidative stress. One caveat was that participants in the mB12/LDFA and BH4 studies had significantly worse markers of glutathione metabolism and chronic oxidative stress at baseline, respectively. Thus, the participants selected in these two clinical trials may have been those with the most severe metabolic abnormalities and most expected to respond to these treatments. Overall this study supports the notion that metabolic abnormalities in individuals with ASD may be amenable to targeted treatments and provide some insight into the mechanism of action of these treatments.
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2. Fatemi SH, Wong DF, Brasic JR, Kuwabara H, Mathur A, Folsom TD, Jacob S, Realmuto GM, Pardo JV, Lee S. {{Metabotropic glutamate receptor 5 tracer [(18)F]-FPEB displays increased binding potential in postcentral gyrus and cerebellum of male individuals with autism: a pilot PET study}}. {Cerebellum & ataxias}. 2018; 5: 3.
Background: Autism is a neurodevelopmental disorder that is first manifested during early childhood. Postmortem experiments have identified significantly elevated expression of metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and prefrontal cortex of individuals with autism. Methods: In the current study we employed the mGluR5 tracer [(18)F]-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([(18)F]-FPEB) to quantify mGluR5 binding in vivo in adults with autism vs. healthy controls using positron emission tomography (PET). Results: We identified significantly higher [(18)F]-FPEB binding potential in the postcentral gyrus and cerebellum of individuals with autism. There was a significant negative correlation between age and [(18)F]-FPEB binding potential in the cerebellum but not in the postcentral gyrus. In the precuneus, [(18)F]-FPEB binding potential correlated positively with the lethargy subscale score for the Aberrant Behavioral Checklist (ABC). In cerebellum, there were significant negative correlations between [(18)F]-FPEB binding potential and ABC total score, ABC hyperactivity subscale score, and the ABC inappropriate speech subscale score. Conclusions: These novel findings demonstrate for the first time that mGluR5 binding is altered in critical brain areas of subjects with autism, suggesting abnormal glutamate signaling in these regions. Finally, the correlations between altered [(18)F]-FPEB binding potential in the cerebellum and precuneus suggest that some autistic symptoms may be influenced by abnormal glutamate signaling.
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3. Fuentes-Albero M, Cauli O. {{Homocysteine levels in autism spectrum disorder: A clinical update}}. {Endocrine, metabolic & immune disorders drug targets}. 2018.
Homocysteine (Hcy) is a non-protein alpha-amino acid, which plays several important roles in human physiology and in the central nervous system. Although Hcy has several known biological properties in one-carbon metabolism, its overproduction might be harmful and could add to the pathophysiology associated with autism spectrum disorder (ASD). This review presents updated information about alterations in the concentration of this amino acid in biological fluids (blood and urine) in patients with ASD. In addition, we assessed its clinical significance by analyzing if there are any potential associations between abnormal Hcy levels and the severity ASD or any of its symptoms. Further research is still needed to correlate the occurrence of increased Hcy levels with specific symptoms/deficits in ASD and to evaluate the clinical impact on ASD of strategies that can reduce the Hcy concentration.
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4. Joseph B, Muralidhar D. {{The scope of parental awareness and mediated training of their children with Autism Spectrum Disorders in India}}. {Asian J Psychiatr}. 2018; 31: 107-8.
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5. Ninci J, Rispoli M, Neely LC, Guz S. {{Transferring picture exchange requests to receptive identification for children with ASD}}. {Dev Neurorehabil}. 2018; 21(3): 178-87.
The purpose of this study was to evaluate a procedure to transfer stimulus control from picture exchange requests to receptive identification. Three children with autism spectrum disorder (ASD) and absent receptive identification repertoires participated. An adapted alternating treatment design was used. During intervention, two high-preferred and two low-preferred targets were available during picture exchange requesting sessions. Participants requested primarily for one or both high-preferred targets. During receptive identification instructional sessions, one participant acquired one high-preferred target, one participant acquired all targets, and one participant demonstrated no improvements. Generalization to novel examples of targets was assessed pre- and post-intervention and programmed if necessary. One participant generalized his acquired high-preferred target without programming. Another participant generalized a high-preferred and a low-preferred target without programming, and acquired a high-preferred target with programming. Potential benefits of this intervention and suggestions for future research are presented.
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6. Rosman NP, Vassar R, Doros G, DeRosa J, Froman A, DiMauro A, Santiago S, Abbott J. {{Association of Prenatal Ultrasonography and Autism Spectrum Disorder}}. {JAMA Pediatr}. 2018.
Importance: The prevalence of autism spectrum disorder (ASD) has been increasing rapidly, with current estimates of 1 in 68 children affected. Simultaneously, use of prenatal ultrasonography has increased substantially, with limited investigation into its safety and effects on brain development. Animal studies have demonstrated that prenatal ultrasonography can adversely affect neuronal migration. Objective: To quantify prenatal ultrasound exposure by the frequency, timing, duration, and strength of ultrasonographic scans in children with later ASD, developmental delay, and typical development. Design, Setting, and Participants: This case-control study included 107 patients with ASD, 104 control individuals with developmental delay, and 209 controls with typical development. Participants were identified from medical records based on prenatal care and delivery at Boston Medical Center, a diverse, academic, safety-net medical center, from July 1, 2006, through December 31, 2014, with a gestational age at birth of at least 37 weeks. Data were analyzed from May 1, 2015, through November 30, 2017. Exposures: Ultrasonographic exposure was quantified by the number and timing of scans, duration of exposure, mean strength (depth, frame rate, mechanical index, and thermal index), and time of Doppler and 3- and 4-dimensional imaging. Main Outcomes and Measures: Among participants with ASD and controls with developmental delay and typical development, ultrasound exposure was quantified and compared per trimester and for the entire pregnancy, with adjustment for infant sex, gestational age at birth, and maternal age. Results: A total of 420 participants were included in the study (328 boys [78.1%] and 92 girls [21.9%]; mean age as of January 1, 2016, 6.6 years; 95% CI, 6.5-6.8 years). The ASD group received a mean of 5.9 scans (95% CI, 5.2-6.6), which was not significantly different from the 6.1 scans (95% CI, 5.4-6.8) in the developmental delay group or the 6.3 scans (95% CI, 5.8-6.8) in the typical development group. Compared with the typical development group, the ASD group had shorter duration of ultrasound exposure during the first (290.4 seconds [95% CI, 212.8-368.0 seconds] vs 406.4 seconds [95% CI, 349.5-463.3 seconds]) and second (1687.6 seconds [95% CI, 1493.8-1881.4 seconds] vs 2011.0 seconds [95% CI, 1868.9-2153.1 seconds]) trimesters but no difference in the number of scans. The ASD group had greater mean depth of ultrasonographic penetration than the developmental delay group in the first trimester (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.1-12.1 cm]). The ASD group had greater mean depth than the typical development group during the first (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.3-12.0 cm]) and the second (12.9 cm [95% CI, 12.6-13.3 cm] vs 12.5 cm [95% CI, 12.2-12.7 cm]) trimesters. Conclusions and Relevance: This study found significantly greater mean depth of ultrasonographic penetration in the ASD group compared with the developmental delay group in the first trimester and compared with the typical development group in the first and second trimesters. Further research is needed to determine whether other variables of ultrasound exposure also have adverse effects on the developing fetus.
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7. Webb SJ, Mourad PD. {{Prenatal Ultrasonography and the Incidence of Autism Spectrum Disorder}}. {JAMA Pediatr}. 2018.
