Margaret L. Bauman

Histoanatomic observations of the brain in early infantile autism

Early infantile autism is a behaviorally defined syndrome that is often associated with abnormalities on neurologic examination and seizures. We report on the brain of a 29-year-old autistic man as compared with that of an age- and sex-matched normal control, using gapless sections of whole brain. Abnormalities were found in the hippocampus, subiculum, entorhinal cortex, septal nuclei, mamillary body, selected nuclei of the amygdala, neocerebellar cortex, roof nuclei of the cerebellum, and inferior olivary nucleus.

Density and Distribution of Hippocampal Neurotransmitter Receptors in Autism: An Autoradiographic Study*

Neuropathological studies in autistic brains have shown small neuronal size and increased cell packing density in a variety of limbic system structures including the hippocampus, a change consistent with curtailment of normal development. Based on these observations in the hippocampus, a series of quantitative receptor autoradiographic studies were undertaken to determine the density and distribution of eight types of neurotransmitter receptors from four neurotransmitter systems (GABAergic, serotoninergic [5-HT], cholinergic, and glutamatergic). Data from these single concentration ligand binding studies indicate that the GABAergic receptor system (3[H]-flunitrazepam labeled benzodiazepine binding sites and 3[H]-muscimol labeled GABAA receptors) is significantly reduced in high binding regions, marking for the first time an abnormality in the GABA system in autism. In contrast, the density and distribution of the other six receptors studied (3[H]-8OH-DPAT labeled 5-HT1A receptors, 3[H]-ketanserin labeled 5-HT2 receptors, 3[H]-pirenzepine labled M1 receptors, 3[H]-hemicholinium labeled high affinity choline uptake sites, 3[H]-MK801 labeled NMDA receptors, and 3[H]-kainate labeled kainate receptors) in the hippocampus did not demonstrate any statistically significant differences in binding.

The anterior cingulate cortex in autism: heterogeneity of qualitative and quantitative cytoarchitectonic features suggests possible subgroups

Autism is a behaviorally defined disorder with deficits in social interaction, communication, atypical behaviors, and restricted areas of interest. Postmortem studies of the brain in autism have shown a broad spectrum of abnormalities in the cerebellum and neocortex, involving limbic regions such as anterior cingulate cortex (ACC, Brodmann’s area 24). Using stereological techniques, we analyzed quantitatively cytoarchitectonic subdomains of the ACC (areas 24a, b, c) with regard to cell packing density and cell size. Microscopic examination of the ACC was also done to identify any neuropathologies. Results showed a significant decrease in cell size in layers I–III and layers V–VI of area 24b and in cell packing density in layers V–VI of area 24c. Direct comparisons revealed irregular lamination in three of nine autism brains and increased density of neurons in the subcortical white matter in the remaining cases. Because previous studies have suggested that von Economo neurons (VENs) may be altered in autism, a preliminary study of their density and size was undertaken. VEN density did not differ between autism and control brains overall. However, among the nine autism cases, there were two subsets; three brains with significantly increased VEN density and the remaining six cases with reduced VEN density compared to controls. Collectively, the findings of this pilot study may reflect the known heterogeneity in individuals with autism and variations in clinical symptomotology. Further neuroanatomic analyses of the ACC, from carefully documented subjects with autism, could substantially expand our understanding of ACC functions and its role in autism.

Parvalbumin‐, calbindin‐, and calretinin‐immunoreactive hippocampal interneuron density in autism

Lawrence YA, Kemper TL, Bauman ML, Blatt GJ. Parvalbumin‐, calbindin‐, and calretinin‐immunoreactive hippocampal interneuron density in autism.u2028Acta Neurol Scand: 2010: 121: 99–108.u2028© 2009 The Authors Journal compilation

Early Intervention for Children With Autism Spectrum Disorder Under 3 Years of Age: Recommendations for Practice and Research

This article reviews current evidence for autism spectrum disorder (ASD) interventions for children aged <3 years, based on peer-reviewed articles published up to December 2013. Several groups have adapted treatments initially designed for older, preschool-aged children with ASD, integrating best practice in behavioral teaching methods into a developmental framework based on current scientific understanding of how infants and toddlers learn. The central role of parents has been emphasized, and interventions are designed to incorporate learning opportunities into everyday activities, capitalize on “teachable moments,” and facilitate the generalization of skills beyond the familiar home setting. Our review identified several comprehensive and targeted treatment models with evidence of clear benefits. Although some trials were limited to 8- to 12-week outcome data, enhanced outcomes associated with some interventions were evaluated over periods as long as 2 years. Based on this review, recommendations are proposed for clinical practice and future research.

Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism

Autism is a developmental disorder with prenatal origins, currently estimated to affect 1 in 91 children in the United States. Social‐emotional deficits are a hallmark of autism and early neuropathology studies have indicated involvement of the limbic system. Imaging studies demonstrate abnormal activation of the posterior cingulate cortex (PCC), a component of the limbic system. Abnormal activation has also been noted in the fusiform gyrus (FFG), a region important for facial recognition and a key element in social interaction. A potential imbalance between excitatory and inhibitory interneurons in the cortex may contribute to altered information processing in autism. Furthermore, reduced numbers of GABA receptors have previously been reported in the autistic brain. Thionin‐stained sections were used to qualitatively assess cytoarchitectonic patterning and quantitatively determine the density of neurons and immunohistochemistry was used to determine the densities of a subset of GABAergic interneurons utilizing parvalbumin‐and calbindin‐immunoreactivity. In autism, the PCC displayed altered cytoarchitecture with irregularly distributed neurons, poorly demarcated layers IV and V, and increased presence of white matter neurons. In contrast, no neuropathology was observed in the FFG. There was no significant difference in the density of thionin, parvalbumin, or calbindin interneurons in either region and there was a trend towards a reduced density of calbindin neurons in the PCC. This study highlights the presence of abnormal findings in the PCC, which appear to be developmental in nature and could affect the local processing of social–emotional behaviors as well as functioning of interrelated areas. Autism Res 2011,4:200–211.

Early identification of autism spectrum disorder: Recommendations for practice and research

Early identification of autism spectrum disorder (ASD) is essential to ensure that children can access specialized evidence-based interventions that can help to optimize long-term outcomes. Early identification also helps shorten the stressful “diagnostic odyssey” that many families experience before diagnosis. There have been important advances in research into the early development of ASDs, incorporating prospective designs and new technologies aimed at more precisely delineating the early emergence of ASD. Thus, an updated review of the state of the science of early identification of ASD was needed to inform best practice. These issues were the focus of a multidisciplinary panel of clinical practitioners and researchers who completed a literature review and reached consensus on current evidence addressing the question “What are the earliest signs and symptoms of ASD in children aged ≤24 months that can be used for early identification?” Summary statements address current knowledge on early signs of ASD, potential contributions and limitations of prospective research with high-risk infants, and priorities for promoting the incorporation of this knowledge into clinical practice and future research.

Early Screening of Autism Spectrum Disorder: Recommendations for Practice and Research.

This article reviews current evidence for autism spectrum disorder (ASD) screening based on peer-reviewed articles published to December 2013. Screening provides a standardized process to ensure that children are systematically monitored for early signs of ASD to promote earlier diagnosis. The current review indicates that screening in children aged 18 to 24 months can assist in early detection, consistent with current American Academy of Pediatrics’ recommendations. We identify ASD-specific and broadband screening tools that have been ev-aluated in large community samples which show particular promise in terms of accurate classification and clinical utility. We also suggest strategies to help overcome challenges to implementing ASD screening in community practice, as well as priorities for future research.

Guidelines for early identification, screening, and clinical management of children with autism spectrum disorders.

Congratulations to the American Academy of Pediatrics (AAP). Two of their recent clinical reports published in Pediatrics , “Identification and Evaluation of Children With Autism Spectrum Disorders”1 and “Management of Children With Autism Spectrum Disorders,”2 will enable pediatricians to address parent concerns sooner, facilitating the early identification of children with autism spectrum disorders (ASDs). As physicians and developmentalists with decades of accumulated experience in working with children with developmental challenges, we applaud and welcome these publications. However, we would like to expand on these reports. In this commentary we (1) describe a broader functional/developmental framework for screening for ASDs, (2) provide a critique of the current trend toward behavioral treatments as primary intervention strategies, and (3) present research evidence for functional/developmental approaches.nnA broader and more refined “functional” developmental framework3 looks for compromises in the childs healthy milestones and helps parents and other caregivers work with the child to improve that area of functioning and overall healthy progression.* This approach helps families identify challenges early in the first and second years of life and to begin to help their children before the 18- and 24-month screenings recommended by the AAP.4 An overfocus on specific problem behaviors without a framework for promoting healthy development may prove to be counterproductive.5nnScreening that focuses on specific behaviors or symptoms (eg, whether a child responds to his or her name toward the end of the first year) may identify a percentage … nnAddress correspondence to Stanley I. Greenspan, MD, 7201 Glenbrook Road, Bethesda, MD 20814. E-mail: stanleygreenspan{at}gmail.com

Early Identification and Interventions for Autism Spectrum Disorder: Executive Summary

* Abbreviations:n ASD — : autism spectrum disordern DSM-5 — : Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition M-CHAT — : Modified Checklist for Autism in ToddlersnnAutism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social communication skills and isolated areas of interest.1 The current prevalence of these disorders is estimated to be 1 in 68,2 and recent estimates of the risk of recurrence in families with at least 1 child diagnosed with ASD are 10% to 19%.3–5 Advances have been made in identifying genetic variants that can account for biological vulnerability to ASD,6,7 although recent studies examining patterns of heredity implicate environmental factors and potential gene-by-environment interactions.8 Although the exact etiology remains unknown in most families, some researchers suggest that the pathogenesis of the disorder begins during prenatal life.9,10 It is likely that ASD is heterogeneous in its etiology as well as in its clinical presentation.11nnThe American Academy of Pediatrics has recommended screening for ASDs at 18 and 24 months of age,12 but recent research suggests that atypical behaviors may be detectable in some children at even younger ages.13,14 However, we are still learning how the timing and developmental course of early ASD symptoms vary across children and how best to detect such symptoms across the continuum of children seen in community practice. In addition, reports15 that early intervention can improve developmental and behavioral outcomes in infants and toddlers have lent urgency to identifying children across the autism spectrum at an earlier age. Advances in genetic, neuroimaging, and other neurobiological research have also raised the potential of biomarker screening. Given the progress in these areas, a review of the current state of the science on early identification, screening, and intervention of ASD was warranted.nnThese issues were the focus of an international, multidisciplinary panel of clinical practitioners and researchers with expertise in ASD and developmental … nnAddress correspondence to Lonnie Zwaigenbaum, MD, Autism Research Center, Glenrose Rehabilitation Hospital, Room E209, 10230 111 Ave, Edmonton, AB, Canada T5G 0B7. E-mail: lonniez{at}ualberta.ca