1. Adams JB, Baral M, Geis E, Mitchell J, Ingram J, Hensley A, Zappia I, Newmark S, Gehn E, Rubin RA, Mitchell K, Bradstreet J, El-Dahr J. {{Safety and Efficacy of Oral DMSA Therapy for Children with Autism Spectrum Disorders: Part B – Behavioral Results}}. {BMC Clin Pharmacol};2009 (Oct 23);9(1):17.
ABSTRACT: BACKGROUND: This study investigated the effects of oral dimercapto succinic acid (DMSA) therapy on the behavioural symptoms of children with autism spectrum disorders (ASD) ages 3-8 years. METHODS: Phase 1 involved 65 children with ASD who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. RESULTS: The groups receiving one round and seven rounds of DMSA had significant improvements on all the assessment measures. The degree of improvement on the assessment measures could be partially explained by a regression analysis based on excretion of toxic metals and changes in glutathione (adjusted R2 of 0.28-0.75, p<0.02 in all cases). One round of DMSA had nearly the same benefit as seven rounds. The assessment measures correlated reasonably with one another at the beginning of the study (r=0.60-0.87) and even better at the end of the study (r=0.63-0.94). CONCLUSIONS: Overall, both one and seven rounds of DMSA therapy seems to be reasonably safe in children with ASD who have high urinary excretion of toxic metals, and possibly helpful in reducing some of the symptoms of autism in those children.
2. Adams JB, Baral M, Geis E, Mitchell J, Ingram J, Hensley A, Zappia I, Newmark S, Gehn E, Rubin RA, Mitchell K, Bradstreet J, El-Dahr J. {{Safety and Efficacy of Oral DMSA Therapy for Children with Autism Spectrum Disorders: Part A – Medical Results}}. {BMC Clin Pharmacol};2009 (Oct 23);9(1):16.
ABSTRACT: BACKGROUND: This study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years. METHODS: Phase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. RESULTS: DMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation. CONCLUSIONS: Overall, DMSA therapy seems to be reasonably safe, effective in removing several toxic metals (especially lead), dramatically effective in normalizing RBC glutathione, and effective in normalizing platelet counts. Only 1 round (3 days) was sufficient to improve glutathione and platelets. Additional rounds increased excretion of toxic metals.
3. Coben R, Linden M, Myers TE. {{Neurofeedback for Autistic Spectrum Disorder: A Review of the Literature}}. {Appl Psychophysiol} Biofeedback;2009 (Oct 24)
There is a need for effective interventions to address the core symptoms and problems associated with autistic spectrum disorder (ASD). Behavior therapy improves communication and behavioral functioning. Additional treatment options include psychopharmacological and biomedical interventions. Although these approaches help children with autistic problems, they may be associated with side effects, risks or require ongoing or long-term treatment. Neurofeedback is a noninvasive approach shown to enhance neuroregulation and metabolic function in ASD. We present a review of the literature on the application of Neurofeedback to the multiple problems associated with ASD. Directions for future research are discussed.
4. Samson AC, Hegenloh M. {{Stimulus Characteristics Affect Humor Processing in Individuals with Asperger Syndrome}}. {J Autism Dev Disord};2009 (Oct 27)
The present paper aims to investigate whether individuals with Asperger syndrome (AS) show global humor processing deficits or whether humor comprehension and appreciation depends on stimulus characteristics. Non-verbal visual puns, semantic and Theory of Mind cartoons were rated on comprehension, funniness and the punchlines were explained. AS individuals did not differ to the control group in humor appreciation of visual puns. However, they had difficulty understanding and appreciating Theory of Mind cartoons and provided mentalistic explanations less frequently than controls suggesting that humor processing is strongly related to the cognitive requirements that the stimuli pose on the perceiver. Furthermore, AS individuals referred in all conditions more frequently to non-joke relevant details. Therefore, humor processing is also influenced by their detail-oriented processing style.
5. Sheikh AM, Li X, Wen G, Tauqeer Z, Brown WT, Malik M. {{Cathepsin D and apoptosis related proteins are elevated in the brain of autistic subjects}}. {Neuroscience};2009 (Oct 22)
Autism is a severe neurodevelopmental disorder characterized by problems in communication, social skills, and repetitive behavior. Recent studies suggest that apoptotic mechanisms may partially contribute to the pathogenesis of this disorder. Cathepsin D is the predominant lysosomal protease and is abundantly expressed in the brain. It plays an important role in regulation of cellular apoptosis and has been shown to mediate apoptosis induced by cytokines TNF-alpha and IFN-gamma. In this study, we examined the expression levels of cathepsin D in the autistic brain. We found that cathepsin D protein expression was significantly increased in the frontal cortex, in pyramidal and granule cells of the hippocampus, and in cerebellar neurons in autistic subjects as compared to controls. In addition, we found that the expression of the anti-apoptotic protein Bcl2 was significantly decreased, while caspase-3, a critical executioner of apoptosis, was increased in the cerebellum of autistic subjects. Previously our studies have shown that Bcl2 expression is decreased and the BDNF-Akt-Bcl2 pathway is compromised in the frontal cortex of autistic subjects, which suggested that increased apoptosis may be involved in the pathogenesis of ASD. Our current finding of decreased Bcl2 and increased capase-3 in the cerebellum of autistic subjects further supports this suggestion. In addition, the finding of increased cathepsin D in the cerebellum of autistic subjects suggests that, through its regulation of apoptosis, the altered activities of cathepsin D in the autistic brain may play an important role in the pathogenesis of autism.
6. Wilson LB, Tregellas JR, Hagerman RJ, Rogers SJ, Rojas DC. A{{ voxel-based morphometry comparison of regional gray matter between fragile X syndrome and autism}}. {Psychiatry Res};2009 (Oct 21)
The phenotypic association between fragile X syndrome (FXS) and autism is well established, but no studies have directly compared whole-brain anatomy between the two disorders. We performed voxel-based morphometry analyses of magnetic resonance imaging (MRI) scans on 10 individuals with FXS, 10 individuals with autism, and 10 healthy comparison subjects to identify volumetric changes in each disorder. Regional gray matter volumes within frontal, parietal, temporal, and cingulate gyri, as well as in the caudate nuclei and cerebellum, were larger in the FXS group relative to the autism group. In addition, volume increases in FXS were observed in frontal gyri and caudate nuclei compared to controls. The autism group exhibited volume increases in frontal and temporal gyri relative to the FXS group, and no volume increases relative to controls. Volumetric deficits relative to controls were observed in regions of the cerebellum for both groups, with additional deficits in parietal and temporal gyri for the FXS group. Our caudate nuclei and frontal gyri results may implicate dysfunction of frontostriatal circuitry in FXS. Cerebellar deficits suggest atypical development of the cerebellum contributing to the phenotype of both disorders, but further imply that unique cerebellar regions contribute to the phenotype of each disorder.
