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PubMed2000

Construction of a physical and transcript map flanking the imprinted MEST/PEG1 region at 7q32.

MEST/PEG1, a gene expressed paternally in mesodermal derivatives in early embryonic stages, is the first imprinted gene mapped to chromosome 7q32. Since imprinted genes are clustered in general at a chromosomal region, we speculated that a similar imprinted-gene cluster may exist at chromosome region 7q32 and that the functions of some such genes may contribute to the phenotype of Silver-Russell syndrome including maternal uniparental disomy for chromosome 7 (maternal UPD7). As an initial step toward the isolation of imprinted genes at 7q32, we adopted an integrated approach involving the construction of a PAC contig and ESTs mapping in the vicinity of MEST. Here, we have constructed a complete contig of PAC and BAC clones and a transcript map spanning the entire approximately 1-Mb region between D7S530 and D7S649. We developed 60 novel STSs and precisely mapped 47 genes/ESTs. This map contains a putative autistic disorder locus that has been suggested to be localized near markers D7S530 and D7S684. This integrated physical and transcript map provides a valuable resource for identification of an imprinted gene(s) in this region as well as a candidate gene(s) for autistic disorder.

Base Sequence↗
PubMed1993

[Mild hearing loss in children with communication disorders].

The prevalence of MHL in 202, 1 to 6 year-old children with communication disorders who visited our clinic in 1991 was investigated. 1) 31% of the subjects had MHL bilaterally. The prevalence of MHL was 44% at age 1 year, 20% at age 2 years, 36% at age 3 years, 24% at age 4 years, 39% at age 5 years, 33% at age 6 years. 2) 88% of children with MHL had OME, 10% had mild sensorineural hearing loss, and 2% had cerminous plug. 3) The prevalence of MHL in children with mental retardation and autistic disorders was 9%, that with stuttering was 9%, that of OME accompanied by moderate and severe hearing disorders was 6%. 4) The primary causes in 191, except for those with stuttering, were as follows; the prevalence of MHL was 30%, that of mental retardation and autistic disorders was 24%, and that of articulation disorders was 28%. 5) On the other hand, the prevalence of MHL in children with retarded language development and articulation disorders was 30%, which was significantly higher than that of the other communication disorders. Accordingly, the results of this study suggest that MHL in early childhood greatly influences communication disorders.

Chi-Square Distribution↗
PubMed1994

Risperidone in the treatment of pervasive developmental disorder.

Elevated concentrations of blood serotonin have been documented in autistic children and mentally retarded adults. Antiserotonergic pharmacotherapy has been partially effective in treating a subgroup of children with autistic disorder. Therefore, the possibility is raised that an antiserotonergic treatment may be of value to adult psychiatric patients with a history of pervasive developmental disorder. Two such cases are described where the patients underwent psychiatric and neuropsychological examination before and after treatment with risperidone, a potent 5-HT2 antagonist with additional D2 antagonistic properties. Particular improvements were documented in both patients, despite long histories of cognitive compromise and high likelihood of damage to the central nervous system.

Adolescent↗
PubMed1990

Social relatedness and autism: current research, issues, directions.

Social relatedness has recently become a primary focus of investigators in the field of autism. This shift to regarding disturbances in social relatedness as one of the defining manifestations of the disorder marks the movement of research on autistic disorder back to its origins, when Kanner first noted the "social and affective" symptoms of autism as pathognomonic. Currently, social impairment in autism is viewed as more pervasively characteristic of the disorder than any other single symptom. Further, there has been a recent proliferation of research designed to document the nature of social deficit in autism, and whether it is primarily affective, communicative, or cognitive in nature, or involves some combination of these three variables. This review summarizes recent research focusing on social relatedness in autism and discusses the implications of these findings.

Autistic Disorder↗
PubMed2001

Conversational characteristics of children with fragile X syndrome: repetitive speech.

The production of repetitive speech during conversations was studied in people with fragile X syndrome, autistic disorder, or mental retardation not caused by fragile X. Repetitive speech was found to be more prevalent among those with fragile X compared to the control groups, especially within atypical utterances. These results suggest that the repetitive speech seen in individuals with fragile X is not the result of either general developmental delay or undiagnosed autistic disorder, and they support our hypothesis that such speech dysfluency reflects the effects of physiological arousal caused by hypersensitivity to social and sensory stimuli. Our results are interpreted within Perkins' theory of neuropsycholinguistic function.

Adolescent↗
PubMed2001

Do autism spectrum disorders differ from each other and from non-spectrum disorders on emotion recognition tests?

We tested whether dimensional measures of empathic ability, theory of mind, and intelligence would differentiate autism spectrum disorders from each other and from non-spectrum disorders. Tests were administered to children with a diagnosis of Autistic Disorder (AutD; n = 20), Asperger's Disorder (AspD; n = 28), Attention Deficit/Hyperactivity Disorder (Inattentive Type) (ADHD; n = 35), Mental Retardation (Mild) (MR; n = 34), Anxiety Disorder (AnxD; n = 14), or No Psychological Disorder (NPD; n = 36). Results showed that empathic ability discriminated among groups on the autism spectrum (AutD < AspD < NPD). Because empathic ability is not independent of intelligence (AutD < AspD < NPD on intelligence; MR < ADHD < NPD on empathic ability), both dimensions are necessary to discriminate autism spectrum from non-spectrum disorders. When intelligence is covaried, empathic ability discriminated AutD, but not AspD, from other disorders (AutD < MR < ADHD < NPD = AnxD = AspD).

Adolescent↗
PubMed2002

Brain anatomy and sensorimotor gating in Asperger's syndrome.

Asperger's syndrome (an autistic disorder) is characterized by stereotyped and obsessional behaviours, and pervasive abnormalities in socio-emotional and communicative behaviour. These symptoms lead to social exclusion and a significant healthcare burden; however, their neurobiological basis is poorly understood. There are few studies on brain anatomy of Asperger's syndrome, and no focal anatomical abnormality has been reliably reported from brain imaging studies of autism, although there is increasing evidence for differences in limbic circuits. These brain regions are important in sensorimotor gating, and impaired 'gating' may partly explain the failure of people with autistic disorders to inhibit repetitive thoughts and actions. Thus, we compared brain anatomy and sensorimotor gating in healthy people with Asperger's syndrome and controls. We included 21 adults with Asperger's syndrome and 24 controls. All had normal IQ and were aged 18-49 years. We studied brain anatomy using quantitative MRI, and sensorimotor gating using prepulse inhibition of startle in a subset of 12 individuals with Asperger's syndrome and 14 controls. We found significant age-related differences in volume of cerebral hemispheres and caudate nuclei (controls, but not people with Asperger's syndrome, had age-related reductions in volume). Also, people with Asperger's syndrome had significantly less grey matter in fronto-striatal and cerebellar regions than controls, and widespread differences in white matter. Moreover, sensorimotor gating was significantly impaired in Asperger's syndrome. People with Asperger's syndrome most likely have generalized alterations in brain development, but this is associated with significant differences from controls in the anatomy and function of specific brain regions implicated in behaviours characterizing the disorder. We hypothesize that Asperger's syndrome is associated with abnormalities in fronto-striatal pathways resulting in defective sensorimotor gating, and consequently characteristic difficulties inhibiting repetitive thoughts, speech and actions.

Adolescent↗
PubMed1976

A pair of classically early infantile autistic siblings.

This case study describes in detail two autistic siblings who were mentioned in Rimland's analysis of checklists for psychotic children, as the only pair of classically early infantile autistic siblings (Rimland, 1971). One of the children, a nonverbal girl, now 13 years old, who developed epileptic seizures at age 41/2, shows all symptoms of early infantile autism even today. Her brother, now 24 years old, however, does not fit any of the known psychopathological patterns of childhood. The boy showed all symptoms of early infantile autism, but also some of the main characteristics of childhood schizophrenia and austic psychopathy. It is suggested that we are dealing perhaps with an unusual mixed type falling within a broad category of genetically determined types of autistic disorders.

Adolescent↗
PubMed2001

A test of central coherence theory: can adults with high-functioning autism or Asperger syndrome integrate fragments of an object?

INTRODUCTION: Visuoconceptual integration was explored as a test of central coherence theory (Frith, 1989). Individuals with autism are thought to have weak central coherence so the prediction was that these individuals would show an impaired ability to integrate visual information. METHOD: Two groups with autistic disorder were recruited: adults with either autism or Asperger syndrome. All were normally intelligent and were matched with members of the general population of Cambridge. A modified version of the Hooper Visual Organisation Test was used in which line drawings depicting simple objects had been cut into pieces and arranged in a puzzle-like fashion. The participants were required to conceptually integrate the fragments in order to identify the object. A second condition presented just a single piece of an object and participants were required to identify objects from a single piece. RESULTS: Both clinical groups were significantly impaired in their ability to integrate pieces holistically, but they were unimpaired in their ability to identify an object from a single piece. CONCLUSION: Individuals with an autistic disorder are less able to integrate visual elements. Of the two clinical groups, the autism group had the greater deficit, and it applied to the majority of the group. Possible explanations for the clinical groups' weak central coherence are explored.

Journal Article↗
PubMed1998

Clinical assessment of adventitious movements.

Many procedures with variable validity and reliability have been developed in research settings to evaluate adventitious movements and related phenomena in specific populations, e.g., people with schizophrenia treated with dopamine antagonists, but these only provide global assessments or rate specific movements. A battery for rating individuals with possible movements disorders in a comprehensive way in clinical settings is needed so a protocol to assess briefly and thoroughly potential movement disorders was videotaped for five prepubertal boys with autistic disorder and severe mental retardation in a clinical trial. Utilizing a Movement Assessment Battery, four raters independently scored videotapes of 10-16 movements assessments of each of the five subjects. Experienced raters attained agreement of 59% to 100% on ratings of tardive dyskinesia and 48% to 100% on tics. Hindrances to reliability included poor quality of some tapes, high activity of subjects, and fatigue of raters.

Autistic Disorder↗
PubMed2006

The yield of subtelomeric FISH analysis in the evaluation of autistic spectrum disorders.

To assess the frequency of cryptic subtelomeric rearrangements in children and adolescents with autism spectrum disorders, blood samples were studied using a complete set of subtelomeric FISH probes in 72 children with autism spectrum disorders. All children had normal high resolution karyotype, DNA fra-X analysis, brain MRI, metabolic work-up, and physical/neurological examination. Subtelomeric analysis did not detect abnormalities in any of the subjects, suggesting the uselessness of such investigations in individuals with primary autism spectrum disorders.

Child↗
PubMed1996

Survey of difficult to contain and treat children and adolescents.

Child psychiatrists and paediatricians are faced by a number of disturbed children and adolescents who become a major treatment challenge due to a combination of their dangerous and/or disruptive behaviour and the unavailability of resources. Paediatricians and psychiatrists in one regional health area were questioned about the number of such children and adolescents under 18 years of age seen over a 20 month period. The response rate was 44% (86/194 specialists approached). A total of 72 children and adolescents were identified. For a health district with a total population of 200,000, this represents nearly five children (about one of these identified by paediatricians and one with associated learning disability). The majority of cases were adolescents with chronic problems (over one month's duration) but most cases reported by paediatricians were acute in preadolescents. Conduct disorders, autistic spectrum, and psychotic disorders were the most common clinical problems. Seriously disruptive behaviour had been present in two thirds and marked problems with behaviour that was a physical risk to others and to the self were present in over half and nearly a third of cases respectively. Services had been universally stretched by these children's difficulties. Clinicians thought the needs of these children would have been best met either through psychiatric day hospital type facilities or in combined paediatric/child psychiatric inpatient units.

Adolescent↗
PubMed1993

Definitional issues and neurobiological foundations of selected severe neurodevelopmental disorders.

This article reviews current definitional issues, selected neuropsychological findings, and presumed neurobiological underpinnings of two of the more commonly identified severe neurodevelopmental disorders: mental retardation and autistic disorder. Although these disorders represent two of the more common severe neurodevelopmental disorders encountered by child neuropsychologists practicing in clinical and research settings, they have not received the amount of attention from the field of neuropsychology as other kinds of neurodevelopmental disorders. Although there are few definitional controversies surrounding these disorders, findings accrued to date reveal solid evidence for neurological processes underlying each of these disorders. In addition, each of these diagnoses likely represents a heterogeneous group of disorders, suggesting that a syndrome analysis approach would prove beneficial for increasing our understanding of each disorder. Conclusions are drawn for the clinician and researcher, particularly with respect to using a neuropsychological perspective and assessment strategies with children with more severe disorders.

Journal Article↗
PubMed2006

Sensorimotor gating deficits in adults with autism.

BACKGROUND: Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and is impaired in a family of neuropsychiatric disorders characterized by abnormalities of inhibitory function. Adults with autistic disorder (AD) exhibit clinical features of inhibitory deficits, such as restrictive and repetitive behaviors, that may be explained by deficits in sensorimotor gating. METHODS: Acoustic startle reactivity, habituation, and PPI (30-, 60-, 120-msec interstimulus intervals) were assessed in 14 adult men diagnosed with AD and 16 typically developing normal comparison (NC) participants. All participants were administered measures of intelligence and frontal-executive functioning. RESULTS: Adults with AD exhibited significantly less PPI in the 60-msec condition than NC participants, which was correlated with increased ratings of restricted and repetitive behaviors. The groups did not differ on measures of startle amplitude or overall habituation. There was, however, a significant group-by-block habituation effect. Furthermore, PPI was not related to intelligence but was moderately associated with performance on a measure of frontal-executive functioning. CONCLUSIONS: Adults with AD have sensorimotor gating deficits similar to other neurodevelopmental disorders, implicating a failure of normal inhibitory regulation of sensory, motor, and attentional mechanisms. Thus, PPI deficits may be indirectly linked to one of the hallmark features of AD.

Acoustic Stimulation↗
PubMed2004

Interrelationship between Autism Diagnostic Observation Schedule-Generic (ADOS-G), Autism Diagnostic Interview-Revised (ADI-R), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) classification in children and adolescents with mental retardation.

The interrelationship between the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule-Generic (ADOS-G) and clinical classification was studied in 184 children and adolescents with Mental Retardation (MR). The agreement between the ADI-R and ADOS-G was fair, with a substantial difference between younger and older children (5-8 vs. 8+ years). Compared with the Diagnostic and Statistical Manual of Mental Disorders-IV-TR (DSM-IV-TR) classification of Autistic Disorder (AD) and Pervasive Developmental Disorder (PDD), both instruments measure AD or PDD validly and reliably. Even in low-functioning children the interrelationship between the instruments and the clinical classification was satisfactory. The combination of ADI-R and ADOS-G identifies AD or PDD, as described in the DSM-IV-TR, most appropriately. Both instruments seem to be of great value in the diagnostic process of PDD in children and adolescents with MR.

Adolescent↗
PubMed2000

Inverse correlation between frontal lobe and cerebellum sizes in children with autism.

Certain cognitive and behavioural deficits suggest that the frontal lobe functions abnormally in patients with autism, but little anatomical research is available to either verify or refute this. In contrast, several neuropathological and neuroimaging studies have demonstrated anatomical abnormalities in the cerebellum in autistic patients. The current study shows that frontal lobe cortex volume is increased in a subset of patients with autism and that this increase correlates with the degree of cerebellar abnormality. This evidence of concurrent structural abnormalities in both the frontal lobe and the cerebellum has important implications for understanding the development and persistence of the autistic disorder.

Autistic Disorder↗
PubMedDate not supplied

[Autism in tuberous sclerosis].

During the last five years, it has been recognized a very high incidence of autism in children affected by tuberous sclerosis; we believe that this association may be more than just a coincidence and that it may be that the autistic behavior spectrum is related to a great extent, to the anatomic localization of tubers in the frontal and temporoparietal areas. In this study we report our experience with 27 consecutive children, 12 boys and 15 girls with a diagnosis of tuberous sclerosis confirmed by clinical and MRI and or CT findings according to the diagnostic criteria developed by the Diagnosis Criteria Committee of the National Tuberous Sclerosis Association. They were studied during the period of 1988 to 1990. Ages range from 18 months to 16 years (mean: 6.5 years). Twenty-four had epilepsy and were receiving antiepileptic treatment. Seven of the 27 children (25.9 per cent) fulfilled the diagnostic criteria for autistic disorder according to the DSM-III-R. The autistic behavior was evident in all of them by three and half years. The seven children had mental retardation. MRI and CT findings with subependymal calcifications and cortical tubers of frontal and temporoparietal predominance were seen in five of the seven autistic children. In one child, CT was normal and in the other it was not performed. Five were girls and all had West syndrome; two were boys and neither had seizures. Most of the reported cases of children with tuberous sclerosis and autism had experiences West syndrome. In our patients, five of the seven children with autism had west syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗