1. Bertoglio K, Jill James S, Deprey L, Brule N, Hendren RL. {{Pilot study of the effect of methyl B12 treatment on behavioral and biomarker measures in children with autism}}. {J Altern Complement Med} (May);16(5):555-560.
Abstract Objectives: The study objectives were to determine whether methyl B12 treatment improves behavioral measures in children with autism and whether improvement is associated with increased plasma concentrations of glutathione (GSH) and an increased redox ratio of reduced glutathione to oxidized glutathione (GSH/GSSG), both of which have been previously identified to be low in children with autism. Design: This was a 12-week, double-blind, placebo-controlled, cross-over clinical trial of injectable methyl B12. Following this 12-week study, subjects were given the option of entering a 6-month open-label trial of methyl B12. Settings/location: All procedures took place at the UC Davis M.I.N.D. Institute. Subjects: Subjects were 3 to 8 years old with autism. Interventions: All subjects received 6 weeks of placebo and 6 weeks of methyl B12 at a dose of 64.5 mcg/kg every three days administered subcutaneously into the buttocks. Outcome measures: Blood for GSH analysis and behavioral assessments were obtained at baseline, week 6, and week 12. Results: Thirty (30) subjects completed the 12-week, double-blind study and 22 subjects completed the 6-month extension study. No statistically significant mean differences in behavior tests or in glutathione status were identified between active and placebo groups. Nine (9) subjects (30%) demonstrated clinically significant improvement on the Clinical Global Impression Scale and at least two additional behavioral measures. More notably, these responders exhibited significantly increased plasma concentrations of GSH and GSH/GSSG. Conclusions: Comparison of the overall means between groups suggests that methyl B12 is ineffective in treating behavioral symptoms of autism. However, detailed data analysis suggests that methyl B12 may alleviate symptoms of autism in a subgroup of children, possibly by reducing oxidative stress. An increase in glutathione redox status (GSH/GSSG) may provide a biomarker for treatment response to methyl B12. Additional research is needed to delineate a subgroup of potential responders and ascertain a biomarker for response to methyl B12.
2. Cheung C, Yu K, Fung G, Leung M, Wong C, Li Q, Sham P, Chua S, McAlonan G. {{Autistic disorders and schizophrenia: related or remote? An anatomical likelihood estimation}}. {PLoS One};5(8)
Shared genetic and environmental risk factors have been identified for autistic spectrum disorders (ASD) and schizophrenia. Social interaction, communication, emotion processing, sensorimotor gating and executive function are disrupted in both, stimulating debate about whether these are related conditions. Brain imaging studies constitute an informative and expanding resource to determine whether brain structural phenotype of these disorders is distinct or overlapping. We aimed to synthesize existing datasets characterizing ASD and schizophrenia within a common framework, to quantify their structural similarities. In a novel modification of Anatomical Likelihood Estimation (ALE), 313 foci were extracted from 25 voxel-based studies comprising 660 participants (308 ASD, 352 first-episode schizophrenia) and 801 controls. The results revealed that, compared to controls, lower grey matter volumes within limbic-striato-thalamic circuitry were common to ASD and schizophrenia. Unique features of each disorder included lower grey matter volume in amygdala, caudate, frontal and medial gyrus for schizophrenia and putamen for autism. Thus, in terms of brain volumetrics, ASD and schizophrenia have a clear degree of overlap that may reflect shared etiological mechanisms. However, the distinctive neuroanatomy also mapped in each condition raises the question about how this is arrived in the context of common etiological pressures.
3. Christ SE, Kanne SM, Reiersen AM. {{Executive function in individuals with subthreshold autism traits}}. {Neuropsychology} (Sep);24(5):590-598.
Objective: Recent research has documented increased psychosocial difficulties in individuals who report higher-than-typical autistic traits but without an Autism Spectrum Disorder (ASD) diagnosis. Less is known, however, regarding the cognitive profile of individuals with subthreshold autism symptomatology. The objective of the present study was to provide additional insight into this issue and examine whether young adults who report higher degrees of autism traits also report experiencing increased difficulties with executive control. Method: The Behavior Rating Inventory of Executive Function was utilized to evaluate behavioral aspects of executive functioning in 66 and 28 individuals who endorsed high and low subthreshold levels of autism symptomatology, respectively. Results: After accounting for Attention Deficit/Hyperactivity Disorder (ADHD) symptomatology at both the group and individual participant levels, we found that autism traits continued to explain a significant amount of variance in participants’ overall level of executive function (Global Executive Composite) as well as within most individual executive domains. Interestingly, the high and low trait groups did not differ on the inhibitory control and organization of materials scales, areas of functioning that appears to be largely spared in individuals with ASD as well. Conclusions: Findings from the present study are consistent with past research linking ASD and executive control impairment. In addition, ASD and ADHD traits were associated with unique contributions to the executive control profile of individuals with subthreshold autism symptomatology. This finding underscores the importance of accounting for ADHD symptomatology in studying ASD. (PsycINFO Database Record (c) 2010 APA, all rights reserved).
4. Nomura Y, Nagao Y, Kimura K, Hachimori K, Segawa M. {{Epilepsy in autism: A pathophysiological consideration}}. {Brain Dev} (Aug 28)
Eighty cases of idiopathic autism with epilepsy and 97 cases without epilepsy were studied to evaluate the pathophysiology of epilepsy in autism. The initial visit to this clinic ranged 8months-30years 3months of age, and the current ages are 5years 8months-42years 3months, 60% reaching to over 30years of age. The average follow up duration is 22.2years+/-9.4years. The ages of onset of epilepsy were from 7months to 30years of age, with the two peaks at 3.2years and 16.7years. EEG central focus appeared earlier than frontal focus. Abnormality of locomotion and atonic NREM were observed more frequently in epileptic group. These suggest the neuronal system related to abnormality of locomotion and atonic NREM, which are the hypofunction of the brainstem monoaminergic system, is the pathomechanism underling the epilepsy in autism. By showing the abnormal sleep-wake rhythm and locomotion being the very initial symptoms in autism, we had shown the hypofunction of the brainstem monoaminergic system is the initial pathomechanism of autism. Thus, epilepsy in autism is not the secondary manifestation, but one of the pathognomonic symptoms of autism. The brainstem monoaminergic system project to the wider cortical area, and the initial monoaminergic hypofunction may lead to the central focus which appears earlier. The failure of the monoaminergic (serotonergic) system causes dysfunction of the pedunculo-pontine nucleus (PPN) and induces dysfunction of the dopamine (DA) system, and with development of the DA receptor supersensitivity consequently disinhibits the thalamo-frontal pathway, which after maturation of this pathway in teens cause the epileptogenesis in the frontal cortex.
5. Wong VC, Sun JG. {{Randomized controlled trial of acupuncture versus sham acupuncture in autism spectrum disorder}}. {J Altern Complement Med} (May);16(5):545-553.
Abstract Objective: We aim to study the efficacy of acupuncture versus sham acupuncture in children with autism spectrum disorder. Methods: A single-blind randomized control trial was conducted in 50 children. These children were randomly assigned to the treatment group with tongue acupuncture (40 sessions over 8 weeks) or the control group (sham tongue acupuncture to nonacupoints in the tongue). Results: There was improvement in both the treatment and control groups in all assessed measures but more so in the treatment than in the control group: (1) eye-hand coordination, performance, and practical reasoning of Griffiths Mental Developmental Scale; (2) sensory-motor, social, affectual, language, and total score of Ritvo-Freeman Real Life Scale; (3) Comprehension Language age in the Reynell Language Developmental Scale; and (4) Total Score and Mental Age in Symbolic Play Test. The only statistically significant improvement in the treatment as compared to the control group was seen in self-care and cognition domains of the Functional Independence Measure for children. Conclusions: We had demonstrated that a short course of acupuncture had efficacy in improving various developmental and behavioral aspects of children with autism. The long-term efficacy in functional gain needs to be further explored.
