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Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Common features between autism spectrum disorders (ASDs) and cancer have been discerned using methodologies from a number of disciplines, including genetics, bioinformatics and epidemiological studies. To understand such apparent overlaps between these two conditions and the mechanisms that may underlie these linkages, it is important to look at their multi-level systems context. Here we discuss ASDs and cancer linkages across levels ranging from genes to pathways and systems, as well as from the vantage points of mechanism and of clinical and epidemiological studies. Review of existing findings yielded evidence that ASDs and cancer overlap extensively in signal transduction pathways that are involved in metabolic processes. We hypothesize that further studies focusing on illuminating the relationships between ASDs and cancer, specifically with regard to signaling pathways that regulate metabolic activities, could help shed new insight on these conditions and develop treatment strategies that, by targeting underlying mechanisms, may be more efficient and effective for both conditions. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is associated with difficulty in processing speech in a noisy background, but the neural mechanisms that underlie this deficit have not been mapped. To address this question, we used magnetoencephalography to compare the cortical responses between ASD and typically developing (TD) individuals to a passive mismatch paradigm. We repeated the paradigm twice, once in a quiet background, and once in the presence of background noise. We focused on both the evoked mismatch field (MMF) response in temporal and frontal cortical locations, and functional connectivity with spectral specificity between those locations. In the quiet condition, we found common neural sources of the MMF response in both groups, in the right temporal gyrus and inferior frontal gyrus (IFG). In the noise condition, the MMF response in the right IFG was preserved in the TD group, but reduced relative to the quiet condition in ASD group. The MMF response in the right IFG also correlated with severity of ASD. Moreover, in noise, we found significantly reduced normalized coherence (deviant normalized by standard) in ASD relative to TD, in the beta band (14-25 Hz), between left temporal and left inferior frontal sub-regions. However, unnormalized coherence (coherence during deviant or standard) was significantly increased in ASD relative to TD, in multiple frequency bands. Our findings suggest increased recruitment of neural resources in ASD irrespective of the task difficulty, alongside a reduction in top-down modulations, usually mediated by the beta band, needed to mitigate the impact of noise on auditory processing. Autism Res 2016,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 631-647. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We report the history of a child with autism and epilepsy who, after limited response to other interventions following her regression into autism, was placed on a gluten-free, casein-free diet, after which she showed marked improvement in autistic and medical symptoms. Subsequently, following pubertal onset of seizures and after failing to achieve full seizure control pharmacologically she was advanced to a ketogenic diet that was customized to continue the gluten-free, casein-free regimen. On this diet, while still continuing on anticonvulsants, she showed significant improvement in seizure activity. This gluten-free casein-free ketogenic diet used medium-chain triglycerides rather than butter and cream as its primary source of fat. Medium-chain triglycerides are known to be highly ketogenic, and this allowed the use of a lower ratio (1.5:1) leaving more calories available for consumption of vegetables with their associated health benefits. Secondary benefits included resolution of morbid obesity and improvement of cognitive and behavioral features. Over the course of several years following her initial diagnosis, the child’s Childhood Autism Rating Scale score decreased from 49 to 17, representing a change from severe autism to nonautistic, and her intelligence quotient increased 70 points. The initial electroencephalogram after seizure onset showed lengthy 3 Hz spike-wave activity; 14 months after the initiation of the diet the child was essentially seizure free and the electroencephalogram showed only occasional 1-1.5 second spike-wave activity without clinical accompaniments. [ABSTRACT FROM AUTHOR]

Abstract: Autism spectrum conditions (ASCs) are defined behaviorally, but they also involve multileveled disturbances of underlying biology that find striking parallels in the physiological impacts of electromagnetic frequency and radiofrequency radiation exposures (EMF/RFR). Part I (Vol 776) of this paper reviewed the critical contributions pathophysiology may make to the etiology, pathogenesis and ongoing generation of behaviors currently defined as being core features of ASCs. We reviewed pathophysiological damage to core cellular processes that are associated both with ASCs and with biological effects of EMF/RFR exposures that contribute to chronically disrupted homeostasis. Many studies of people with ASCs have identified oxidative stress and evidence of free radical damage, cellular stress proteins, and deficiencies of antioxidants such as glutathione. Elevated intracellular calcium in ASCs may be due to genetics or may be downstream of inflammation or environmental exposures. Cell membrane lipids may be peroxidized, mitochondria may be dysfunctional, and various kinds of immune system disturbances are common. Brain oxidative stress and inflammation as well as measures consistent with blood–brain barrier and brain perfusion compromise have been documented. Part II of this paper documents how behaviors in ASCs may emerge from alterations of electrophysiological oscillatory synchronization, how EMF/RFR could contribute to these by de-tuning the organism, and policy implications of these vulnerabilities. It details evidence for mitochondrial dysfunction, immune system dysregulation, neuroinflammation and brain blood flow alterations, altered electrophysiology, disruption of electromagnetic signaling, synchrony, and sensory processing, de-tuning of the brain and organism, with autistic behaviors as emergent properties emanating from this pathophysiology. Changes in brain and autonomic nervous system electrophysiological function and sensory processing predominate, seizures are common, and sleep disruption is close to universal. All of these phenomena also occur with EMF/RFR exposure that can add to system overload (‘allostatic load’) in ASCs by increasing risk, and can worsen challenging biological problems and symptoms; conversely, reducing exposure might ameliorate symptoms of ASCs by reducing obstruction of physiological repair. Various vital but vulnerable mechanisms such as calcium channels may be disrupted by environmental agents, various genes associated with autism or the interaction of both. With dramatic increases in reported ASCs that are coincident in time with the deployment of wireless technologies, we need aggressive investigation of potential ASC—EMF/RFR links. The evidence is sufficient to warrant new public exposure standards benchmarked to low-intensity (non-thermal) exposure levels now known to be biologically disruptive, and strong, interim precautionary practices are advocated. [Copyright &y& Elsevier]

Although Autism Spectrum Disorders (ASD) are generally assumed to be lifelong, we review evidence that between 3% and 25% of children reportedly lose their ASD diagnosis and enter the normal range of cognitive, adaptive and social skills. Predictors of recovery include relatively high intelligence, receptive language, verbal and motor imitation, and motor development, but not overall symptom severity. Earlier age of diagnosis and treatment, and a diagnosis of Pervasive Developmental Disorder-Not Otherwise Specified are also favorable signs. The presence of seizures, mental retardation and genetic syndromes are unfavorable signs, whereas head growth does not predict outcome. Controlled studies that report the most recovery came about after the use of behavioral techniques. Residual vulnerabilities affect higher-order communication and attention. Tics, depression and phobias are frequent residual co-morbidities after recovery. Possible mechanisms of recovery include: normalizing input by forcing attention outward or enriching the environment; promoting the reinforcement value of social stimuli; preventing interfering behaviors; mass practice of weak skills; reducing stress and stabilizing arousal. Improving nutrition and sleep quality is non-specifically beneficial. [ABSTRACT FROM AUTHOR]

Data sharing in autism neuroimaging presents scientific, technical, and social obstacles. We outline the desiderata for a data-sharing scheme that combines imaging with other measures of phenotype and with genetics, defines requirements for comparability of derived data and recommendations for raw data, outlines a core protocol including multispectral structural and diffusion-tensor imaging and optional extensions, provides for the collection of prospective, confound-free normative data, and extends sharing and collaborative development not only to data but to the analytical tools and methods applied to these data. A theme in these requirements is the need to preserve creative approaches and risk-taking within individual laboratories at the same time as common standards are provided for these laboratories to build on. [ABSTRACT FROM AUTHOR]

In this article we address analytic challenges inherent in brain volumetrics (i.e., the study of volumes of brains and brain regions). It has sometimes been assumed in the literature that deviations in regional brain size in clinical samples are directly related to maldevelopment or pathogenesis. However, this assumption may be incorrect; such volume differences may, instead, be wholly or partly attributable to individual differences in overall dimension (e.g., for head, brain, or body size). What quantitative approaches can be used to take these factors into account? Here, we provide a review of volumetric and nonvolumetric adjustment factors. We consider three examples of common statistical methods by which one can adjust for the effects of body, head, or brain size on regional volumetric measures: the analysis of covariance , the proportion , and the residual approaches. While the nature of the adjustment will help dictate which method is most appropriate, the choice is context sensitive, guided by numerous considerations—chiefly the experimental hypotheses, but other factors as well (including characteristic features of the disorder and sample size). These issues come into play in logically framing the assessment of putative abnormalities in regional brain volumes. [ABSTRACT FROM AUTHOR]

The most replicated finding in autism neuroanatomy--a tendency to unusually large brains--has seemed paradoxical in relation to the specificity of the abnormalities in three behavioral domains that define autism. We now know a range of things about this phenomenon, including that brains in autism have a growth spurt shortly after birth and then slow in growth a few short years afterward, that only younger but not older brains are larger in autism than in controls, that white matter contributes disproportionately to this volume increase and in a nonuniform pattern suggesting postnatal pathology, that functional connectivity among regions of autistic brains is diminished, and that neuroinflammation (including microgliosis and astrogliosis) appears to be present in autistic brain tissue from childhood through adulthood. Alongside these pervasive brain tissue and functional abnormalities, there have arisen theories of pervasive or widespread neural information processing or signal coordination abnormalities (such as weak central coherence, impaired complex processing, and underconnectivity), which are argued to underlie the specific observable behavioral features of autism. This convergence of findings and models suggests that a systems- and chronic disease-based reformulation of function and pathophysiology in autism needs to be considered, and it opens the possibility for new treatment targets. [ABSTRACT FROM AUTHOR]

Abstract: The interface of developmental neuroimaging with developmental neurotoxicology can, broadly speaking, address two complementary concerns. The first is to study the impact of specific exposures on brain development. The second is to study known neurobehavioral disorders with an eye to discerning toxicological contributions to pathogenesis. Pathogenesis targets brain based upon physical properties (receptors, growth factors, etc.) while behavior is modulated by regional and neural systems alterations. The distribution of pathogenesis-brain relationships overlaps only partially with that of brain-behavior relationships. The goal of this paper is to highlight methodological issues involved in designing and interpreting volumetric neuroimaging studies in the light of this loose coupling. [Copyright &y& Elsevier]

Social and emotional processing uses neural systems involving structures ranging from the brain stem to the associational cortex. Neuroimaging research has attempted to identify abnormalities in components of these systems that would underlie the behavioral abnormalities seen in disorders of social and emotional processing, notably autism spectrum disorders, the focus of this review. However, the findings have been variable. The most replicated anatomic finding (a tendency toward large brains) is not modular, and metabolic imaging and functional imaging (although showing substantial atypicality in activation) are not consistent regarding specific anatomic sites. Moreover, autism spectrum disorder demonstrates substantial heterogeneity on multiple levels. Here evidence is marshaled from a review of neuroimaging data to support the claim that abnormalities in social and emotional processing on the autism spectrum are a consequence of systems disruptions in which the behaviors are a final common pathway and the focal findings can be variable, downstream of other pathogenetic mechanisms, and downstream of more pervasive abnormalities. (J Child Neurol 2004;19:772-784). [ABSTRACT FROM AUTHOR]

The article presents the author's views on the contradiction in opinions concerning the etiology of autism. The author blames brain research for taking a piecemeal approach to autism, as it analyzed specific regions of the brain to find out causes that might explain the specific behavioral deficits. He deplores over the maltreatment meted out by the medical establishment to autistic patients because of a sense that autism is a hopeless and incurable brain condition.

Background The non-prescription medication paracetamol (acetaminophen, APAP) is currently recommended as a safe pain and fever treatment during pregnancy. However, recent studies suggest a possible association between APAP use in pregnancy and offspring neurodevelopment. Objectives To conduct a review of publications reporting associations between prenatal APAP use and offspring neurodevelopmental outcomes. Methods Relevant sources were identified through a key word search of multiple databases (Medline, CINAHL, OVID and TOXNET) in September 2016. All English language observational studies of pregnancy APAP and three classes of neurodevelopmental outcomes (autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intelligence quotient (IQ)) were included. One reviewer (AZB) independently screened all titles and abstracts, extracted and analyzed the data. Results 64 studies were retrieved and 55 were ineligible. Nine prospective cohort studies fulfilled all inclusion criteria. Data pooling was not appropriate due to heterogeneity in outcomes. All included studies suggested an association between prenatal APAP exposure and the neurodevelopmental outcomes; ADHD, ASD, or lower IQ. Longer duration of APAP use was associated with increased risk. Associations were strongest for hyperactivity and attention-related outcomes. Little modification of associations by indication for use was reported. Conclusions Together, these nine studies suggest an increased risk of adverse neurodevelopmental outcomes following prenatal APAP exposure. Further studies are urgently needed with; precise indication of use and exposure assessment of use both in utero and in early life. Given the current findings, pregnant women should be cautioned against indiscriminate use of APAP. These results have substantial public health implications. [ABSTRACT FROM AUTHOR]

Background: Twenty years of research on early intensive treatment using applied behavior analysis (ABA) for children with autism has consistently produced robust effects. There appears to be a subset of children whose response to intensive ABA treatments includes achieving a level of functioning that is indistinguishable from typically developing peers. The purpose of this study was to describe a subset of children who recovered from autism following intensive ABA interventions. Methods: We reviewed the clinical files of 38 children with autism who achieved an optimal outcome after receiving intensive ABA services. results: The mean age at intake was 40 months. Average IQ was 83.6 at intake and 107.9 at discharge. Mean adaptive skills were 68.04 at intake and 88.87 at discharge. Conclusions: Our study corroborates the finding that some children with autism who receive early intensive behavioral intervention achieve functioning in the average range. [ABSTRACT FROM AUTHOR]