Autism as a Developmental Neurobiological Disorder: New Insights from Functional Neuroimaging

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1 Oxford Medicine Online You are looking at 1-10 of 35 items for: pathophysiology mental disorder MED00810 MED00160 Autism as a Developmental Neurobiological Disorder: New Insights from Functional Neuroimaging Nancy J. Minshew, K. Suzanne Scherf, Marlene Behrmann, and Katherine Humphreys DOI: /med/ This chapter calls for a paradigm shift in the study of autism in order to address the most pressing questions about how genetic and developmental neurobiological findings can be integrated with findings about the characterization of the behavioral syndrome. The chapter is organized as follows. First, it provides a brief review of the current neurobehavioral theories of autism. Second, it challenges these theories by reviewing current evidence, particularly from longitudinal studies of infants at high risk for developing autism, which challenges the notion of a single causative behavioral or cognitive feature of the syndrome or even a cluster of core causative behavioral or cognitive features. Third, it proposes that research on autism spectrum disorders would benefit from taking the perspective that autism is a developmental neurobiological disorder, rather than a behavioral or single systems disorder. Finally, it describes a program of research in the domain of visual processing that illustrates the strength of this interdisciplinary approach to uncover novel relations between the behavioral and brain bases of autism, and that supports the claim that disruptions to neural connectivity are a fundamental contributing factor to the etiology of autism. Comorbid Obsessive-Compulsive Disorders Bonnie P. Taylor and Eric Hollander DOI: /med/ This chapter focuses on the overlap of repetitive, restricted, and/or stereotyped patterns of behavior, interests, and/or activities that characterize both autism spectrum disorders (ASD) and related obsessive-compulsive spectrum disorders (OCSDs) including obsessivecompulsive disorder, obsessive-compulsive personality disorder, body dysmorphic disorder, and trichotillomania. The chapter is organized as follows. First, it outlines the symptomatic commonalities in repetitive behaviors between ASD and other OCSDs. Next, it summarizes research findings related to the frequent comorbidity, similar course, and potentially overlapping genetic, neurobiological, and neuropsychological correlates across these disorders. Finally, it presents different approaches to subtyping the diverse symptoms that Page 1 of 5

2 comprise the repetitive behavior domain. The identification of homogeneous subgroups will arm investigators with more power to uncover the unique pathogenesis that underlies each repetitive phenotype. Pharmacotherapy for Autism Spectrum Disorders James T. McCracken DOI: /med/ Children, adolescents, and adults with the full range of the autism spectrum disorders (ASDs) are frequently referred for possible pharmacologic treatment for an array of associated difficult-to-manage behaviors, and to support adaptation and progress from other forms of interventions. This chapter reviews the available evidence for each of the major drug classes, as well as information regarding their safety and optimal use. It discusses current recommendations based on the best evidence available for the largest and most commonly presented targets for treatment in individuals with ASDs. Finally, it describes future directions for drug development in ASDs based on emerging models of etio-pathophysiology of ASDs and related conditions. Epilepsy and Electroencephalography in Autism Spectrum Disorders Roberto Tuchman DOI: /med/ This chapter reviews studies on the prevalence of epilepsy and epileptiform activity in autism spectrum disorders (ASD). The wide range of co-occurrence of seizures and epileptic activity is dependent on multiple variables that include age, presence of genetic syndrome or underlying brain pathology, and degree of intellectual disability. The best estimate of the prevalence on epilepsy in ASD is 8% in ASD without significant intellectual disability and 20% in ASD with intellectual disability. The prevalence of epileptiform activity in individuals with ASD and no clinical history of seizures is approximately 6% to 30% and is dependent on the type of electroencephalography (EEG) study done, the length of the EEG recording, methodology specific to collecting and interpretation of EEGs, and the specific population of children with ASD being studied. The prevalence of epilepsy and of epileptiform activity is significantly higher greater than 50% in those with severe intellectual disability, genetic syndromes, and other associated brain pathology. An emerging consensus is that shared genetic and molecular mechanisms account for the common co-occurrence of ASD and epilepsy. Page 2 of 5

3 Repetitive Behaviors in Individuals with Autism Spectrum Disorders James W. Bodfish DOI: /med/ Repetitive behaviors frequently dominate the daily activity of autistic children, can significantly interfere with opportunities to develop functional behaviors, and are frequently the target of intervention and treatment. A central theme in the recent research findings in repetitive behavior is that while all cases by definition have expressed repetitive behaviors, several distinct subtypes of repetitive behavior appear to exist across persons with autism spectrum disorders. This chapter discusses the phenomenology, pathogenesis, and interventions for repetitive behaviors. Rare Genetic Variants and Autism Spectrum Disorders Hande Kaymakçalan and Matthew W. State DOI: /med/ This chapter discusses the contribution of rare and very rare genetic variation to autism spectrum disorders (ASD). The first section provides a basic background into the nature of genetic variation and distinctions between common and rare alleles. The second describes two competing, but not necessarily mutually exclusive, hypotheses about the genomic underpinnings of ASD, the common-variant: common-disease hypothesis and the rarevariant: common-disease hypothesis. The section third addresses the so-called outlier strategy of gene discovery, in which the focus is on rare and very rare alleles irrespective of their overall contribution to population risk. The fourth addresses the emerging evidence regarding the cumulative contribution of rare variation to ASD, including a consideration of opportunities and challenges facing current efforts to tackle this question. Finally, the chapter considers recent rare variant discoveries that have raised the prospect that a given specific genetic mutation may contribute to a broad spectrum of neuropsychiatric and neurodevelopmental outcomes ranging from ASD to mental retardation, seizure, and schizophrenia. Autism Spectrum Disorders: Looking Backward and Looking Forward Michael Rutter DOI: /med/ There have been huge changes in the understanding of autistic spectrum disorders, and research findings have clarified a range of crucial questions that, at the same time, presents many further challenges. This chapter begins with a summary of some of the main research Page 3 of 5

4 accomplishments to date, then proceeds to outline a range of challenges that remain. Throughout, there is an emphasis on research findings and research challenges that have potentially important clinical implications. Motor Functioning and Dyspraxia in Autism Spectrum Disorders Matthew W. Mosconi, Yukari Takarae, and John A. Sweeney DOI: /med/ Investigations of neurobehavioral aspects of autism spectrum disorders (ASD) primarily has focused on an analysis of abnormalities in complex cognitive operations including social cognition, communication, and executive functioning, which represent the defining clinical characteristics of the disorder. However, recent behavioral, neurophysiological, neuroimaging, and histological evidence suggests that motor system development is also abnormal in ASD. These observations highlight the need for systematic investigation of the developmental trajectory and causes of atypical motor function and dyspraxia in these disorders. This chapter reviews studies on motor system neurophysiology and its dysfunction in ASD; vestibular modulation of motor control in ASD; gross motor impairments in individuals with ASD; fine motor impairments in individuals with ASD; oculomotor impairments in ASD; evidence of dsypraxia in ASD; motor development in infants and young children with ASD; and factors associated with motor deficits in ASD. Diagnosis and Assessment of Autism Spectrum Disorders: A Medical Perspective Daniel L. Coury DOI: /med/ This chapter discusses the medical aspects of autism spectrum disorders (ASDs), and their influence on diagnosis, assessment, and treatment. As part of a multidisciplinary diagnostic evaluation for autism, which typically includes a pediatrician, psychologist, speechlanguage pathologist, and occupational therapist, the medical evaluation is a key component that can inform not only diagnosis but treatment. A thorough developmental and family history should be taken with the goal of identifying risk factors for developmental disorders including autism. The developmental history should include prenatal conditions that affect the developing fetus, perinatal experiences, and conditions or illnesses encountered in infancy and childhood. The medical assessment also should address any coexisting functional complaints. Concerns seen most frequently in children with ASDs include gastrointestinal and related nutritional status, sleep issues, innate immunity or risk for infectious diseases, and general behaviors such as stereotypies or hyperactivity. Psychiatric comorbidities such as ADHD, anxiety, and depression are very common, especially in older children and adolescents. Page 4 of 5

5 Commentary: Future Directions in the Treatment of Autism Spectrum Disorders Evdokia Anagnostou, Mark F. Bear, and Geraldine Dawson DOI: /med/ This commentary considers current challenges, gaps, and future directions of with autism spectrum disorders (ASD) treatment research, including research on neuropsychopharmacological and behavioral/psychosocial interventions for ASD. Emerging data from basic science (neuropathology, genetics/genomics/proteomics, animal models) have made it possible to start identifying neurochemical systems involved in the pathophysiology of autism that can be specifically targeted with neuropsychopharmacological interventions. It is anticipated that, ultimately, pharmacological agents targeting systems involved in the pathophysiology of ASD will be used to facilitate existing behavioral interventions. Page 5 of 5