1. Chawarska K, Campbell D, Chen L, Shic F, Klin A, Chang J. {{Early generalized overgrowth in boys with autism}}. {Arch Gen Psychiatry};2011 (Oct);68(10):1021-1031.
CONTEXT: Multiple studies have reported an overgrowth in head circumference (HC) in the first year of life in autism. However, it is unclear whether this phenomenon is independent of overall body growth and whether it is associated with specific social or cognitive features. OBJECTIVES: To examine the trajectory of early HC growth in autism compared with control groups; to assess whether HC growth in autism is independent of height and weight growth during infancy; and to examine HC growth from birth to 24 months in relationship to social, verbal, cognitive, and adaptive functioning levels. DESIGN: Retrospective study. SETTING: A specialized university-based clinic. PARTICIPANTS: Boys diagnosed as having autistic disorder (n = 64), pervasive developmental disorder-not otherwise specified (n = 34), global developmental delay (n = 13), and other developmental problems (n = 18) and typically developing boys (n = 55). MAIN OUTCOME MEASURES: Age-related changes in HC, height, and weight between birth and age 24 months; measures of social, verbal, and cognitive functioning at age 2 years. RESULTS: Compared with typically developing controls, boys with autism were significantly longer by age 4.8 months, had a larger HC by age 9.5 months, and weighed more by age 11.4 months (P = .05 for all). None of the other clinical groups showed a similar overgrowth pattern. Boys with autism who were in the top 10% of overall physical size in infancy exhibited greater severity of social deficits (P = .009) and lower adaptive functioning (P = .03). CONCLUSIONS: Boys with autism experienced accelerated HC growth in the first year of life. However, this phenomenon reflected a generalized process affecting other morphologic features, including height and weight. The study highlights the importance of studying factors that influence not only neuronal development but also skeletal growth in autism.
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2. Flaherty DK. {{The vaccine-autism connection: a public health crisis caused by unethical medical practices and fraudulent science}}. {Ann Pharmacother};2011 (Oct);45(10):1302-1304.
In 1998, Dr. Andrew Wakefield, a British gastroenterologist, described a new autism phenotype called the regressive autism-enterocolitis syndrome triggered by environmental factors such as measles, mumps, and rubella (MMR) vaccination. The speculative vaccination-autism connection decreased parental confidence in public health vaccination programs and created a public health crisis in England and questions about vaccine safety in North America. After 10 years of controversy and investigation, Dr. Wakefield was found guilty of ethical, medical, and scientific misconduct in the publication of the autism paper. Additional studies showed that the data presented were fraudulent. The alleged autism-vaccine connection is, perhaps, the most damaging medical hoax of the last 100 years.
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3. Ghanizadeh A. {{Could fever and neuroinflammation play a role in the neurobiology of autism? A subject worthy of more research}}. {Int J Hyperthermia};2011 (Oct 3)
Autism is neuropsychiatric disorder in which a hyperglutamate state may play a role. It is suggested here that fever or hyperthermia may be able to alter glutamate levels in the brain and may therefore be able to impact on the symptoms of autism. More study on this possibility is clearly warranted.
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4. Gomot M, Wicker B. {{A challenging, unpredictable world for people with Autism Spectrum Disorder}}. {Int J Psychophysiol};2011 (Oct 1)
Autism is a pervasive neurodevelopmental disorder characterized by impairment of communication and social interaction, as well as by high levels of repetitive and ritualistic behaviours. This last dimension results in major difficulties in daily life: clinical reports of individuals with Autism Spectrum Disorder (ASD) show that they present tantrums as a response to change, or restricted interests and repetitive behaviours in order to prevent or minimize change. Such a crucial need to maintain sameness suggests substantial differences in how the ASD brain predicts the environment, and this might have a fundamental role in the deficit revealed in the highly unpredictable social world. Several lines of evidence indicating difficulties in generating or using predictions in ASD due to atypical information processing will be presented in this review. For instance, several studies have revealed that people with ASD demonstrate a unique profile of cognitive abilities, with strategies that depend to an abnormally large extent on sensory systems, at the expense of more integrative processing requiring an awareness of contextual subtleties necessary for prediction. At a more elementary level, patients with autism manifest unusual processing of unpredictable events, which might be rooted in a basic difference in how the brain orients to changing, novel sensory stimuli. This review presents results from ERPs and fMRI studies illustrating the psychophysiological mechanisms and neural bases underlying such phenomena in ASD. We propose that such dysfunction in the ability to build flexible prediction in ASD may originate from impaired top-down influence over a variety of sensory and higher level information processing, a physiopathological hypothesis which dovetails with the cortical under connectivity current theory.
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5. Horev G, Ellegood J, Lerch JP, Son YE, Muthuswamy L, Vogel H, Krieger AM, Buja A, Henkelman RM, Wigler M, Mills AA. {{Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism}}. {Proc Natl Acad Sci U S A};2011 (Oct 3)
Recurrent copy number variations (CNVs) of human 16p11.2 have been associated with a variety of developmental/neurocognitive syndromes. In particular, deletion of 16p11.2 is found in patients with autism, developmental delay, and obesity. Patients with deletions or duplications have a wide range of clinical features, and siblings carrying the same deletion often have diverse symptoms. To study the consequence of 16p11.2 CNVs in a systematic manner, we used chromosome engineering to generate mice harboring deletion of the chromosomal region corresponding to 16p11.2, as well as mice harboring the reciprocal duplication. These 16p11.2 CNV models have dosage-dependent changes in gene expression, viability, brain architecture, and behavior. For each phenotype, the consequence of the deletion is more severe than that of the duplication. Of particular note is that half of the 16p11.2 deletion mice die postnatally; those that survive to adulthood are healthy and fertile, but have alterations in the hypothalamus and exhibit a « behavior trap » phenotype-a specific behavior characteristic of rodents with lateral hypothalamic and nigrostriatal lesions. These findings indicate that 16p11.2 CNVs cause brain and behavioral anomalies, providing insight into human neurodevelopmental disorders.
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6. Hunsaker MR, Greco CM, Spath MA, Smits AP, Navarro CS, Tassone F, Kros JM, Severijnen LA, Berry-Kravis EM, Berman RF, Hagerman PJ, Willemsen R, Hagerman RJ, Hukema RK. {{Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice}}. {Acta Neuropathol};2011 (Oct);122(4):467-479.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder generally presenting with intention tremor and gait ataxia, but with a growing list of co-morbid medical conditions including hypothyroidism, hypertension, peripheral neuropathy, and cognitive decline. The pathological hallmark of FXTAS is the presence of intranuclear inclusions in both neurons and astroglia. However, it is unknown to what extent such inclusions are present outside the central nervous system (CNS). To address this issue, we surveyed non-CNS organs in ten human cases with FXTAS and in a CGG repeat knock-in (CGG KI) mouse model known to possess neuronal and astroglial inclusions. We find inclusions in multiple tissues from FXTAS cases and CGG KI mice, including pancreas, thyroid, adrenal gland, gastrointestinal, pituitary gland, pineal gland, heart, and mitral valve, as well as throughout the associated autonomic ganglia. Inclusions were observed in the testes, epididymis, and kidney of FXTAS cases, but were not observed in mice. These observations demonstrate extensive involvement of the peripheral nervous system and systemic organs. The finding of intranuclear inclusions in non-CNS somatic organ systems, throughout the PNS, and in the enteric nervous system of both FXTAS cases as well as CGG KI mice suggests that these tissues may serve as potential sites to evaluate early intervention strategies or be used as diagnostic factors.
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7. Siniscalco D, Sapone A, Giordano C, Cirillo A, de Novellis V, de Magistris L, Rossi F, Fasano A, Maione S, Antonucci N. {{The Expression of Caspases is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients}}. {J Autism Dev Disord};2011 (Oct 4)
Autism and autism spectrum disorders (ASDs) are heterogeneous complex neuro-developmental disorders characterized by dysfunctions in social interaction and communication skills. Their pathogenesis has been linked to interactions between genes and environmental factors. Consistent with the evidence of certain similarities between immune cells and neurons, autistic children also show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the activation of caspases, cysteinyl aspartate-specific proteases involved in apoptosis and several other cell functions in PBMCs from 15 ASD children compared to age-matched normal healthy developing controls. The mRNA levels for caspase-1, -2, -4, -5 were significantly increased in ASD children as compared to healthy subjects. Protein levels of Caspase-3, -7, -12 were also increased in ASD patients. Our data are suggestive of a possible role of the capsase pathway in ASD clinical outcome and of the use of caspase as potential diagnostic and/or therapeutic tools in ASD management.
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8. Thomas Curtis J, Chen Y, Buck DJ, Davis RL. {{Chronic inorganic mercury exposure induces sex-specific changes in central TNFalpha expression: Importance in autism?}}. {Neurosci Lett};2011 (Oct 17);504(1):40-44.
Mercury is neurotoxic and increasing evidence suggests that environmental exposure to mercury may contribute to neuropathologies including Alzheimer’s disease and autism spectrum disorders. Mercury is known to disrupt immunocompetence in the periphery, however, little is known about the effects of mercury on neuroimmune signaling. Mercury-induced effects on central immune function are potentially very important given that mercury exposure and neuroinflammation both are implicated in certain neuropathologies (i.e., autism). Furthermore, mounting evidence points to the involvement of glial activation in autism. Therefore, we utilized an in vivo model to assess the effects of mercury exposure on neuroimmune signaling. In prairie voles, 10 week mercury exposure (60ppm HgCl(2) in drinking water) resulted in a male-specific increase in TNFalpha protein expression in the cerebellum and hippocampus. These findings are consistent with our previously reported male-specific mercury-induced deficits in social behavior and further support a role for heavy metals exposure in neuropathologies such as autism. Subsequent studies should further evaluate the mechanism of action and biological consequences of heavy metals exposure. Additionally, these observations highlight the potential of neuroimmune markers in male voles as biomarkers of environmental mercury toxicity.
