著者: Daniel H Geschwind, Pat Levitt
雑誌名: Curr Opin Neurobiol. 2007 Feb;17(1):103-11. doi: 10.1016/j.conb.2007.01.009. Epub 2007 Feb 1.
Abstract/Text
Autism is a common and heterogeneous childhood neurodevelopmental disorder. Analogous to broad syndromes such as mental retardation, autism has many etiologies and should be considered not as a single disorder but, rather, as 'the autisms'. However, recent genetic findings, coupled with emerging anatomical and functional imaging studies, suggest a potential unifying model in which higher-order association areas of the brain that normally connect to the frontal lobe are partially disconnected during development. This concept of developmental disconnection can accommodate the specific neurobehavioral features that are observed in autism, their emergence during development, and the heterogeneity of autism etiology, behaviors and cognition.
PMID
17275283 Curr Opin Neurobiol. 2007 Feb;17(1):103-11. doi: 10.101･･･
著者: Francesca Happé, Angelica Ronald, Robert Plomin
雑誌名: Nat Neurosci. 2006 Oct;9(10):1218-20. doi: 10.1038/nn1770.
Abstract/Text
We argue that there will be no single (genetic or cognitive) cause for the diverse symptoms defining autism. We present recent evidence of behavioral fractionation of social impairment, communication difficulties and rigid and repetitive behaviors. Twin data suggest largely nonoverlapping genes acting on each of these traits. At the cognitive level, too, attempts at a single explanation for the symptoms of autism have failed. Implications for research and treatment are discussed.
PMID
17001340 Nat Neurosci. 2006 Oct;9(10):1218-20. doi: 10.1038/nn17･･･
著者: Kunio Miyake, Takae Hirasawa, Tsuyoshi Koide, Takeo Kubota
雑誌名: Adv Exp Med Biol. 2012;724:91-8. doi: 10.1007/978-1-4614-0653-2_7.
Abstract/Text
Autism was previously thought to be caused by environmental factors. However, genetic factors are now considered to be more contributory to the pathogenesis of autism, based on the recent findings of mutations in the genes which encode synaptic molecules associated with the communication between neurons. Epigenetic is a mechanism that controls gene expression without changing DNA sequence but by changing chromosomal histone modifications and its abnormality is associated with several neurodevelopmental diseases. Since epigenetic modifications are known to be affected by environmental factors such as nutrition, drugs and mental stress, autistic diseases are not only caused by congenital genetic defects, but may also be caused by environmental factors via epigenetic mechanism. In this chapter, we introduce autistic diseases caused by epigenetic failures and discuss epigenetic changes by environmental factors and discuss new treatments for neurodevelopmental diseases based on the recent epigenetic findings.
PMID
22411236 Adv Exp Med Biol. 2012;724:91-8. doi: 10.1007/978-1-461･･･
著者: D L Robins, D Fein, M L Barton, J A Green
雑誌名: J Autism Dev Disord. 2001 Apr;31(2):131-44.
Abstract/Text
Autism, a severe disorder of development, is difficult to detect in very young children. However, children who receive early intervention have improved long-term prognoses. The Modified Checklist for Autism in Toddlers (M-CHAT), consisting of 23 yes/no items, was used to screen 1,293 children. Of the 58 children given a diagnostic/developmental evaluation, 39 were diagnosed with a disorder on the autism spectrum. Six items pertaining to social relatedness and communication were found to have the best discriminability between children diagnosed with and without autism/PDD. Cutoff scores were created for the best items and the total checklist. Results indicate that the M-CHAT is a promising instrument for the early detection of autism.
PMID
11450812 J Autism Dev Disord. 2001 Apr;31(2):131-44.
著者: U Frith, F Happé
雑誌名: Cognition. 1994 Apr-Jun;50(1-3):115-32.
Abstract/Text
The theory of mind account of autism has been remarkably successful in making specific predictions about the impairments in socialization, imagination and communication shown by people with autism. It cannot, however, explain either the non-triad features of autism, or earlier experimental findings of abnormal assets and deficits on non-social tasks. These unexplained aspects of autism, and the existence of autistic individuals who consistently pass false belief tasks, suggest that it may be necessary to postulate an additional cognitive abnormality. One possible abnormality-weak central coherence--is discussed, and preliminary evidence for this theory is presented.
PMID
8039356 Cognition. 1994 Apr-Jun;50(1-3):115-32.
著者: G Rizzolatti, L Fadiga, V Gallese, L Fogassi
雑誌名: Brain Res Cogn Brain Res. 1996 Mar;3(2):131-41.
Abstract/Text
In area F5 of the monkey premotor cortex there are neurons that discharge both when the monkey performs an action and when he observes a similar action made by another monkey or by the experimenter. We report here some of the properties of these 'mirror' neurons and we propose that their activity 'represents' the observed action. We posit, then, that this motor representation is at the basis of the understanding of motor events. Finally, on the basis of some recent data showing that, in man, the observation of motor actions activate the posterior part of inferior frontal gyrus, we suggest that the development of the lateral verbal communication system in man derives from a more ancient communication system based on recognition of hand and face gestures.
PMID
8713554 Brain Res Cogn Brain Res. 1996 Mar;3(2):131-41.
著者: Lindsay M Oberman, Edward M Hubbard, Joseph P McCleery, Eric L Altschuler, Vilayanur S Ramachandran, Jaime A Pineda
雑誌名: Brain Res Cogn Brain Res. 2005 Jul;24(2):190-8. doi: 10.1016/j.cogbrainres.2005.01.014.
Abstract/Text
Autism spectrum disorders (ASD) are largely characterized by deficits in imitation, pragmatic language, theory of mind, and empathy. Previous research has suggested that a dysfunctional mirror neuron system may explain the pathology observed in ASD. Because EEG oscillations in the mu frequency (8-13 Hz) over sensorimotor cortex are thought to reflect mirror neuron activity, one method for testing the integrity of this system is to measure mu responsiveness to actual and observed movement. It has been established that mu power is reduced (mu suppression) in typically developing individuals both when they perform actions and when they observe others performing actions, reflecting an observation/execution system which may play a critical role in the ability to understand and imitate others' behaviors. This study investigated whether individuals with ASD show a dysfunction in this system, given their behavioral impairments in understanding and responding appropriately to others' behaviors. Mu wave suppression was measured in ten high-functioning individuals with ASD and ten age- and gender-matched control subjects while watching videos of (1) a moving hand, (2) a bouncing ball, and (3) visual noise, or (4) moving their own hand. Control subjects showed significant mu suppression to both self and observed hand movement. The ASD group showed significant mu suppression to self-performed hand movements but not to observed hand movements. These results support the hypothesis of a dysfunctional mirror neuron system in high-functioning individuals with ASD.
PMID
15993757 Brain Res Cogn Brain Res. 2005 Jul;24(2):190-8. doi: 10･･･
著者: Lindsay M Oberman, Vilayanur S Ramachandran, Jaime A Pineda
雑誌名: Neuropsychologia. 2008 Apr;46(5):1558-65. doi: 10.1016/j.neuropsychologia.2008.01.010. Epub 2008 Jan 19.
Abstract/Text
In an early description of the mu rhythm, Gastaut and Bert [Gastaut, H. J., & Bert, J. (1954). EEG changes during cinematographic presentation. Clinical Neurophysiology, 6, 433-444] noted that it was blocked when an individual identified himself with an active person on the screen, suggesting that it may be modulated by the degree to which the individual can relate to the observed action. Additionally, multiple recent studies suggest that the mirror neurons system (MNS) is impaired in individuals with autism spectrum disorders (ASD), which may affect their ability to relate to others. The current study aimed to investigate MNS sensitivity by examining mu suppression to familiarity, i.e., the degree to which the observer is able to identify with the actor on the screen by using familiar versus unfamiliar actors. The participants viewed four 80s videos that included: (1) stranger: an unfamiliar hand performing a grasping action; (2) familiar: the child's guardian or sibling's hand performing the same action; (3) own: the participant's own hand performing the same action; (4) bouncing balls: two balls moving vertically toward and away from each other. The study revealed that mu suppression was sensitive to degree of familiarity. Both typically developing participants and those with ASD showed greater suppression to familiar hands compared to those of strangers. These findings suggest that the MNS responds to observed actions in individuals with ASD, but only when individuals can identify in some personal way with the stimuli.
PMID
18304590 Neuropsychologia. 2008 Apr;46(5):1558-65. doi: 10.1016/･･･
著者: Atsushi Senju, Victoria Southgate, Sarah White, Uta Frith
雑誌名: Science. 2009 Aug 14;325(5942):883-5. doi: 10.1126/science.1176170. Epub 2009 Jul 16.
Abstract/Text
Adults with Asperger syndrome can understand mental states such as desires and beliefs (mentalizing) when explicitly prompted to do so, despite having impairments in social communication. We directly tested the hypothesis that such individuals nevertheless fail to mentalize spontaneously. To this end, we used an eye-tracking task that has revealed the spontaneous ability to mentalize in typically developing infants. We showed that, like infants, neurotypical adults' (n = 17 participants) eye movements anticipated an actor's behavior on the basis of her false belief. This was not the case for individuals with Asperger syndrome (n = 19). Thus, these individuals do not attribute mental states spontaneously, but they may be able to do so in explicit tasks through compensatory learning.
PMID
19608858 Science. 2009 Aug 14;325(5942):883-5. doi: 10.1126/scie･･･
著者: L Wing, J Gould
雑誌名: J Autism Dev Disord. 1979 Mar;9(1):11-29.
Abstract/Text
The prevalence, in children aged under 15, of severe impairments of social interaction, language abnormalities, and repetitive stereotyped behaviors was investigated in an area of London. A "socially impaired" group (more than half of whom were severely retarded) and a comparison group of "sociable severely mentally retarded" children were identified. Mutism or echolalia, and repetitive stereotyped behaviors were found in almost all the socially impaired children, but to a less marked extent in a minority of the sociable severely retarded. Certain organic conditions were found more often in the socially impaired group. A subgroup with a history of Kanner's early childhood autism could be identified reliably but shared many abnormalities with other socially impaired children. The relationships between mental retardation, typical autism, and other conditions involving social impairment were discussed, and a system of classification based on quality of social interaction was considered.
PMID
155684 J Autism Dev Disord. 1979 Mar;9(1):11-29.
著者: Mats Cederlund, Christopher Gillberg
雑誌名: Dev Med Child Neurol. 2004 Oct;46(10):652-60.
Abstract/Text
The objective of this study was to investigate the background and associated factors in a representative group of young males with Asperger syndrome (AS) presenting at a specialized autism clinic. One hundred males aged 5 years 6 months to 24 years 6 months, with a mean age of 11 years 4 months (SD 3y 10mo), who had a clinical diagnosis of AS were included in the study. An in-depth review of their medical records and neuropsychological test data was performed. There was a high rate (51%) of non-verbal learning disability (defined as Verbal IQ more than 15 points higher than Performance IQ), but otherwise there was little or no support for the notion of right-hemisphere brain dysfunction being at the core of the syndrome. There was a very high rate of close relatives with autism spectrum problems, but also high rates of prenatal and perinatal problems, including prematurity and postmaturity. In comparison with general population data, those with AS very often had a combination of genetic and prenatal and perinatal risk factors. Non-verbal learning disability test results applied in about half the group. There was a subgroup of individuals with AS who had macrocephalus. However, there was no support for an association of AS with low body mass index.
PMID
15473168 Dev Med Child Neurol. 2004 Oct;46(10):652-60.
著者: Hitoshi Hara
雑誌名: Brain Dev. 2007 Sep;29(8):486-90. doi: 10.1016/j.braindev.2006.12.012. Epub 2007 Feb 26.
Abstract/Text
So-called "idiopathic" autism, which exhibited no major complications before diagnosis is well-known as one of the risk factors for epilepsy. This retrospective follow-up study aimed to clarify the characteristics of epilepsy in the autism; onset of seizure, seizure types, EEG findings and epilepsy outcome and the differences as a group between the autism with epilepsy and those without epilepsy. One hundred thirty individuals with autistic disorder or atypical autism diagnosed in childhood were followed up over 10 years and were evaluated almost every year up to 18-35 years of age. Their medical records related to perinatal conditions, IQ, social maturity scores and several factors of epilepsy were reviewed in October 2005. Thirty-three of the follow-up group (25%) exhibited epileptic seizures. The onset of epilepsy was distributed from 8 to 26 years of age. Two types of seizure were observed; partial seizure with secondarily generalized seizure and generalized seizure. Twenty of the epileptics (61%) showed the partial seizure. Although 18% of the non-epileptic group exhibited epileptic discharges on EEG, 68% of the epileptic group revealed epileptiform EEG findings before the onset of epilepsy. No differences were observed concerning the sex ratio, autistic disorder/atypical autism and past history of febrile seizures between the epileptic and non-epileptic groups. Lower IQ, lower social maturity score and higher frequency of prescribed psychotropics were observed in the epileptic group compared to the non-epileptics. Idiopathic autism was confirmed as the high risk factor for epilepsy. Epileptiform EEG findings predict subsequent onset of epileptic seizures in adolescence. Epilepsy is one of negative factors on cognitive, adaptive and behavioral/emotional outcomes for individuals with autism.
PMID
17321709 Brain Dev. 2007 Sep;29(8):486-90. doi: 10.1016/j.braind･･･
著者: Danielle C Llaneza, Susan V DeLuke, Myra Batista, Jacqueline N Crawley, Kristin V Christodulu, Cheryl A Frye
雑誌名: Physiol Behav. 2010 Jun 1;100(3):268-76. doi: 10.1016/j.physbeh.2010.01.003. Epub 2010 Jan 21.
Abstract/Text
Autism spectrum disorders (ASD) affect approximately 1 in 150 children across the U.S., and are characterized by abnormal social actions, language difficulties, repetitive or restrictive behaviors, and special interests. ASD include autism (autistic disorder), Asperger Syndrome, and Pervasive Developmental Disorder not otherwise specified (PDD-NOS or atypical autism). High-functioning individuals may communicate with moderate-to-high language skills, although difficulties in social skills may result in communication deficits. Low-functioning individuals may have severe deficiencies in language, resulting in poor communication between the individual and others. Behavioral intervention programs have been developed for ASD, and are frequently adjusted to accommodate specific individual needs. Many of these programs are school-based and aim to support the child in the development of their skills, for use outside the classroom with family and friends. Strides are being made in understanding the factors contributing to the development of ASD, particularly the genetic contributions that may underlie these disorders. Mutant mouse models provide powerful research tools to investigate the genetic factors associated with ASD and its co-morbid disorders. In support, the BTBR T+tf/J mouse strain incorporates ASD-like social and communication deficits and high levels of repetitive behaviors. This commentary briefly reviews the reciprocal relationship between observations made during evidence-based behavioral interventions of high- versus low-functioning children with ASD and the accumulating body of research in autism, including animal studies and basic research models. This reciprocity is one of the hallmarks of the scientific method, such that research may inform behavioral treatments, and observations made during treatment may inform subsequent research.
Copyright 2010 Elsevier Inc. All rights reserved.
PMID
20093134 Physiol Behav. 2010 Jun 1;100(3):268-76. doi: 10.1016/j･･･
著者: S L Smalley
雑誌名: Am J Hum Genet. 1997 Jun;60(6):1276-82. doi: 10.1086/515485.
Abstract/Text
PMID
9199546 Am J Hum Genet. 1997 Jun;60(6):1276-82. doi: 10.1086/51･･･
著者: Scott M Myers, Chris Plauché Johnson, American Academy of Pediatrics Council on Children With Disabilities
雑誌名: Pediatrics. 2007 Nov;120(5):1162-82. doi: 10.1542/peds.2007-2362. Epub 2007 Oct 29.
Abstract/Text
Pediatricians have an important role not only in early recognition and evaluation of autism spectrum disorders but also in chronic management of these disorders. The primary goals of treatment are to maximize the child's ultimate functional independence and quality of life by minimizing the core autism spectrum disorder features, facilitating development and learning, promoting socialization, reducing maladaptive behaviors, and educating and supporting families. To assist pediatricians in educating families and guiding them toward empirically supported interventions for their children, this report reviews the educational strategies and associated therapies that are the primary treatments for children with autism spectrum disorders. Optimization of health care is likely to have a positive effect on habilitative progress, functional outcome, and quality of life; therefore, important issues, such as management of associated medical problems, pharmacologic and nonpharmacologic intervention for challenging behaviors or coexisting mental health conditions, and use of complementary and alternative medical treatments, are also addressed.
PMID
17967921 Pediatrics. 2007 Nov;120(5):1162-82. doi: 10.1542/peds.･･･
著者: O I Lovaas
雑誌名: J Consult Clin Psychol. 1987 Feb;55(1):3-9.
Abstract/Text
PMID
3571656 J Consult Clin Psychol. 1987 Feb;55(1):3-9.
著者: Serena Wieder, Stanley I Greenspan
雑誌名: Autism. 2003 Dec;7(4):425-35. doi: 10.1177/1362361303007004008.
Abstract/Text
The developmental, individual-difference, relationship-based model (DIR), a theoretical and applied framework for comprehensive intervention, examines the functional developmental capacities of children in the context of their unique biologically based processing profile and their family relationships and interactive patterns. As a functional approach, it uses the complex interactions between biology and experience to understand behavior and articulates the developmental capacities that provide the foundation for higher order symbolic thinking and relating. During spontaneous 'floor time' play sessions, adults follow the child's lead utilizing affectively toned interactions through gestures and words to move the child up the symbolic ladder by first establishing a foundation of shared attention, engagement, simple and complex gestures, and problem solving to usher the child into the world of ideas and abstract thinking. This process is illustrated by a case example of a young boy on the autism spectrum interacting with his father during 'floor time' over a 3 year period.
PMID
14678681 Autism. 2003 Dec;7(4):425-35. doi: 10.1177/136236130300･･･
