ISSN:1080-4013    

DOI:10.1002/mrdd.20037

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2004

数据来源: WILEY

摘要:

AbstractThe goal of this review of the research literature is to discuss approaches to the early detection of autism in infancy. Early detection would enable diagnoses to be made before 18 months of age rather than at 24–30 months, the age where diagnoses start to be made now. After summarizing the criteria for a deficit to be considered “core” to the disorder, the literature on research strategies used in early detection is examined. In order to guide the design of future studies, the review then turns to an overview of what is known about the processes of early social development in typically developing children that underlie the domains in which core deficits are manifested in young children with autism. The social domains covered in the review are those that show development in typically developing infants below 18 months of age: dyadic interaction and imitation; emotion discrimination; and attachment. The review concludes that all of these areas are worthy of investigation in young children, particularly those at higher risk of showing some of the core deficits of autism such as the infant siblings of children with autism. © 2004 Wiley‐Liss, Inc. MRDD Research Reviews 2004;10

ISSN:1080-4013    

DOI:10.1002/mrdd.20046

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2004

数据来源: WILEY

摘要:

AbstractThis article seeks to elucidate the trajectory of development in adolescents and adults with autism. Prospective, retrospective, and cross‐sectional studies are reviewed to reveal the manifestation of and changes in the core symptoms of autism in adolescence and adulthood. Comparing children with adolescents and adults, modest degrees of symptom abatement and improvement in skills have been documented in multiple studies, as are increases in verbal and decreases in performance IQ. Nevertheless, most individuals do not attain normative outcomes in adulthood and continue to manifest significant degrees of symptomatology and dependency. However, a small sub‐group (about 15%) has more favorable adult outcomes. © 2004 Wiley‐Liss, Inc. MRDD Research Reviews 2004;10:2

ISSN:1080-4013    

DOI:10.1002/mrdd.20038

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2004

数据来源: WILEY

摘要:

AbstractThe importance of genetic factors in autism has prompted the development of mutant mouse models to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (1) face validity, i.e., resemblance to the human symptoms; (2) construct validity, i.e., similarity to the underlying causes of the disease; and (3) predictive validity, i.e., expected responses to treatments that are effective in the human disease. There is a growing need for mouse behavioral tasks with all three types of validity for modeling the symptoms of autism. We are in the process of designing a set of tasks with face validity for the defining features of autism: deficits in appropriate reciprocal social interactions, deficits in verbal social communication, and high levels of ritualistic repetitive behaviors. Social approach is tested in an automated three‐chambered apparatus that offers the subject a choice between a familiar environment, a novel environment, and a novel environment containing a stranger mouse. Preference for social novelty is tested in the same apparatus, with a choice between the start chamber, the chamber containing a familiar mouse, and the chamber containing a stranger mouse. Social communication is evaluated by measuring the ultrasonic distress vocalizations emitted by infant mouse pups and the parental response of retrieving the pup to the nest. Resistance to change in ritualistic repetitive behaviors is modeled by forcing a change in habit, including reversal of the spatial location of a reinforcer in a T‐maze task and in the Morris water maze. Mouse behavioral tasks that may model additional features of autism are discussed, including tasks relevant to anxiety, seizures, sleep disturbances, and sensory hypersensitivity. Applications of these tests include (1) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism, (2) characterization of mutant mice derived from random chemical mutagenesis, (3) DNA microarray analyses of genes in inbred strains of mice that differ in social interaction, social communication and resistance to change in habit, and (4) evaluation of proposed therapeutics for the treatment of autism. Published 2004 Wiley‐Liss, Inc. MRDD Research Reviews 2004;10:24

ISSN:1080-4013    

DOI:10.1002/mrdd.20039

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2004

数据来源: WILEY

摘要:

AbstractIn this review article, we summarize recent progress toward understanding the neural structures and circuitry underlying dysfunctional social cognition in autism. We review selected studies from the growing literature that has used the functional neuroimaging techniques of cognitive neuroscience to map out the neuroanatomical substrates of social cognition in autism. We also draw upon functional neuroimaging studies with neurologically normal individuals and individuals with brain lesions to highlight the insights these studies offer that may help elucidate the search for the neural basis of social cognition deficits in autism. We organize this review around key brain structures that have been implicated in the social cognition deficits in autism: (1) the amygdala, (2) the superior temporal sulcus region, and (3) the fusiform gyrus. We review some of what is known about the contribution of each structure to social cognition and then review autism studies that implicate that particular structure. We conclude with a discussion of several potential future directions in the cognitive neuroscience of social deficits in autism. © 2004 Wiley‐Liss, Inc. MRDD Research Reviews 2004;10:259

ISSN:1080-4013    

DOI:10.1002/mrdd.20040

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2004

数据来源: WILEY

摘要:

AbstractAutism is a heritable disorder characterized by phenotypic and genetic complexity. This review begins by surveying current linkage, gene association, and cytogenetic studies performed with the goal of identifying autism disease susceptibility variants. Though numerous linkages and associations have been identified, they tend to diminish upon closer examination or attempted replication. The review therefore explores challenges to current methodologies presented by the complexities of autism that might underlie some of the current difficulties, and finishes by describing emerging phenotypic, statistical, and molecular investigational approaches that offer hope of overcoming those challenges. © 2004 Wiley‐Liss, Inc. MRDD Research Reviews 2004;10:272

ISSN:1080-4013    

DOI:10.1002/mrdd.20041

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2004

数据来源: WILEY

摘要:

AbstractNew insights into biological factors that underlie autism may be gained by comparing autism to other neurodevelopmental disorders that have autistic features and relatively well‐delineated genetic etiologies or neurobiological findings. This review moves beyond global diagnoses of autism and instead uses an endophenotypic approach to compare specific clusters of autistic symptomatology to features of chromosome 15q11‐q13 disorders. Paternally or maternally derived deficiencies of 15q11‐q13 result in Prader‐Willi or Angelman syndromes, and we first use a global approach to review potential autism susceptibility genes in the 15q11‐q13 region. We then use a more trait‐based approach to suggest possible ties between specific phenotypic characteristics of autism and Prader‐Willi syndrome, namely savant‐like skills. We conclude with insights from pathophysiological studies that implicate altered development of specific neuron types and circuits in the cerebral cortex as part of the pathophysiological processes associated with autism and mental retardation. © 2004 Wiley‐Liss, Inc. MRDD Research Revie

ISSN:1080-4013    

DOI:10.1002/mrdd.20042

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2004

数据来源: WILEY

摘要:

AbstractThe potential role of environmental factors in autism spectrum disorders (ASD) is an area of emerging interest within the public and scientific communities. The high degree of heritability of ASD suggests that environmental influences are likely to operate through their interaction with genetic susceptibility during vulnerable periods of development. Evaluation of the plausibility of specific neurotoxicants as etiological agents in ASD should be guided by toxicological principles, including dose–effect dependency and pharmacokinetic parameters. Clinical and epidemiological investigations require the use of sufficiently powered study designs with appropriate control groups and unbiased case ascertainment and exposure assessment. Although much of the existing data that have been used to implicate environmental agents in ASD are limited by methodological shortcomings, a number of efforts are underway that will allow more rigorous evaluation of the role of environmental exposures in the etiology and/or phenotypic expression of the disorder. Surveillance systems are now in place that will provide reliable prevalence estimates going forward in time. Anticipated discoveries in genetics, brain pathology, and the molecular/cellular basis of functional impairment in ASD are likely to provide new opportunities to explore environmental aspects of this disorder. © 2004 Wiley‐Liss, Inc. MRDD Research Reviews 2004;10:292

ISSN:1080-4013    

DOI:10.1002/mrdd.20043

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2004

数据来源: WILEY

摘要:

AbstractAutism is a complex, behaviorally defined, developmental brain disorder with an estimated prevalence of 1 in 1,000. It is now clear that autism is not a disease, but a syndrome with a strong genetic component. The etiology of autism is poorly defined both at the cellular and the molecular levels. Based on the fact that seizure activity is frequently associated with autism and that abnormal evoked potentials have been observed in autistic individuals in response to tasks that require attention, several investigators have recently proposed that autism might be caused by an imbalance between excitation and inhibition in key neural systems including the cortex. Despite considerable ongoing effort toward the identification of chromosome regions affected in autism and the characterization of many potential gene candidates, only a few genes have been reproducibly shown to display specific mutations that segregate with autism, likely because of the complex polygenic nature of this syndrome. Among those, several candidate genes have been shown to control the early patterning and/or the late synaptic maturation of specific neuronal subpopulations controlling the balance between excitation and inhibition in the developing cortex and cerebellum. In the present article, we review our current understanding of the developmental mechanisms patterning the balance between excitation and inhibition in the context of the neurobiology of autism. © 2004 Wiley‐Liss, Inc. MRDD Research Reviews 2004;10:303

ISSN:1080-4013    

DOI:10.1002/mrdd.20044

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2004

数据来源: WILEY

摘要:

AbstractA wide variety of nonestablished treatments have been proposed as “cures” for the core features of autism and are used frequently despite having largely escaped scientific scrutiny. In contrast, a growing body of empirical evidence supports the use of a few forms of theory‐based and empirically validated treatment for some aspects of the core features of autism. These include behavioral/psychoeducational interventions and specific forms of medication treatment, which can produce significant improvements in communication, social interaction, and problem behaviors that both maintain over time and generalize across settings. While there is no doubt that treatment and educational services for persons with autism have improved over the past 6 decades, it also appears that significant issues remain with respect to (1) the routine application of validated treatments for the majority of cases with autism, (2) the resistance to even validated forms of treatment for a substantial minority of cases with autism, and (3) the extent to which validated treatments effectively treat the specific core features of autism that are most disabling for persons with autism and their families. © 2004 Wiley‐Liss, Inc. MRDD Research Reviews 2004;10

ISSN:1080-4013    

DOI:10.1002/mrdd.20045

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2004

数据来源: WILEY