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PubMed1991

Toward DSM-IV: a developmental approach to autistic disorder.

As a developmental disorder, autism presents as a combination of unusually delayed maturational stages constrained by neuropathology that also produces many atypical behaviors. This process was labeled atypical ontogeny. To understand the development of autistic symptoms, it is necessary to consider each behavior in the context of what is normal for the child's nonverbal mental age and then the extent to which the behavior is delayed or atypical, given factors such as degree of delay, function, and frequency of expression. Many symptoms of autism are not unique to autism, and many reflect at least in part the underlying degree of mental retardation present in a large proportion of autistic individuals. Given this, it is important to rate autistic symptoms in the context of the child's mental development in areas of intelligence not specifically affected by the autism (i.e., nonverbal intelligence) in order to be sure that the symptom is characteristic of autism and not just reflective of the degree of mental retardation. In order to do this, the clinician must have a good understanding of the normal milestones in development in each of the areas in which autistic children develop symptoms. Developmental examples of both normal and atypical milestones, as well as a reliable indicator of nonverbal level of development, would help a user of the DSM-IV criteria for autistic disorder make more accurate decisions in reaching a diagnosis. The DSM-III-R criteria for autistic disorder have many other problems, such as lack of certain kinds of reliability and validity, poor specificity, and redundancy. Discussion of these problems is beyond the scope of this article but is presented elsewhere. What have been presented here are recommendations for revising DSM-III-R diagnostic criteria for autistic disorder insofar as there are implications for putting developmental psychopathology into a developmental context.

Autistic Disorder↗

PubMed2003

Parental identification of early behavioural abnormalities in children with autistic disorder.

The aim of the study was to identify early behavioural abnormalities in children later diagnosed with autistic disorder. Accurate identification of such deficits has implications for early diagnosis, intervention and prognosis. The parents of 153 children with autistic disorder completed a questionnaire asking them to describe early childhood behaviours of concern and to recall the age of onset. Core deficit-linked behaviours were then identified and the ontogeny of their development was noted. Behaviour categories were: (1) gross motor difficulties, (2) social awareness and play deficits, (3) language and communication difficulties, and (4) unusual preoccupations. The findings supported the notion that the nature and prevalence of these deficits depend on age. Consistent with past research, there was a significant interval between parents first noticing abnormalities and the making of a definitive diagnosis. The implications for this delay are discussed.

Adolescent↗

PubMed2004

Behaviour profiles in a population of infants later diagnosed as having autistic disorder.

In order to complement findings in the field of early autism and in the context of our studies on the quantitative neurobiological evaluation of patients with autism, we studied a large population of infants later diagnosed as having autistic disorder, using multivariate descriptive statistical methods. The population included 74 infants between six and 35 months, evaluated with the Infant Behavioural Summarised Evaluation (IBSE) scale. Thirteen of the 33 items of the IBSE scale were selected according to previous studies on older patients with autistic disorder. Correspondence analysis was applied to these 13 items, followed by a classical cluster analysis. This procedure permitted the identification of four different profiles which were distinguished on the basis of five main behaviours: activity, auditory perception, sensorimotility, eye contact and use of objects. These profiles are similar to those identified in older children with autism. This study provides an objective description of early clinical markers of the heterogeneity in autism and thus contributes to the description of the onset of autistic disorder. It identified more precise clinical subtyping which will be valuable for future bioclinical studies.

Autistic Disorder↗

PubMed1992

Differential response of seven subjects with autistic disorder to clomipramine and desipramine.

OBJECTIVE: Clomipramine, a serotonin reuptake blocker that has unique antiobsessional properties, was hypothesized to have a different effect from that of desipramine, a tricyclic antidepressant with selective adrenergic effects, for the stereotyped, repetitive behaviors in autism. METHOD: Seven subjects, ages 6-18 years, with autistic disorder completed a 10-week double-blind, crossover trial of clomipramine and desipramine following a 2-week single-blind, placebo phase. RESULTS: Clomipramine was superior to desipramine and placebo, as indicated by standardized ratings of autism and anger as well as ratings of repetitive and compulsive behaviors. Clomipramine and desipramine were equally superior to placebo for ratings of hyperactivity. Parents of all seven subjects elected to have their children continue to take clomipramine after the study. CONCLUSIONS: Clomipramine and desipramine are differentially effective in treating the obsessive-compulsive and core symptoms in autistic disorder. Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.

Adolescent↗

PubMed1990

Autistic disorder in Sotos syndrome: a case report.

A case study of a child with Sotos syndrome, normal intelligence, and autistic disorder is presented. Initial descriptions of Sotos syndrome included severe to mild mental retardation. More recent studies indicate language and learning disabilities with normal intelligence. Our patient met criteria for a diagnosis of autistic disorder. Sotos syndrome is another genetic and neurodevelopmental syndrome that can be associated with autistic as well as communication and language disorders.

Autistic Disorder↗

PubMed2005

Intervention,treatmentand care in autistic disorder. Challenging case reports from northern Finland.

OBJECTIVES: Autism produces characteristic patterns of behaviour, and individuals with autistic disorder (AD) have a lot in common in terms of behaviour and mannerisms. Individuals with autism, however, also have their own overall personalities, which both underlie and interact with their autism. This article focuses on challenges of identifying AD and delivering appropriate services in face of long distances and limited resources. STUDY DESIGN: This study is a retrospective descriptive chart review and cases series. Hospital records and data on the treatment/habilitation status of 187 children and adolescents with autistic disorder aged 3-18 years were evaluated from Northern Finland. METHODS: Nine subjects, representing the age group of 9- to 17-year-olds, did not show any improvement on the Childhood Autism Rating Scale (CARS) and in the clinical examination during the follow-up period 1990--97. In this study, these children and adolescents with AD were evaluated more carefully. RESULTS: The treatment programs and therapies varied, depending on the availability of trained staff. There were various reasons for the absence of the most suitable treatment, or habilitation, at the individual level. The difficulties also varied over time and between individuals. In addition, after the follow-up period, four of the nine (55.6%) individuals showed more positive outcome when the level of autism had been taken into account in the planning of the intervention for, treatment and care of AD. CONCLUSION: The possible reasons for poor outcome included the level of mental disability, impairments of speech and communication, lack of knowledge of autism at the municipal level, long distance to services, severe epilepsy, additional medical diagnosis, parental acceptance of the child's autism and late start of the intervention for, or habilitation of autism.

Adolescent↗

PubMed1998

[Low-dose levodopa therapy of autistic disorder: evaluation of clinical effectiveness].

Based upon the hypothesis that brain monoamine metabolism is disorganized in some children with an autistic disorder, we tried low dose levodopa therapy (0.5 mg/kg/day) proposed by Segawa, et al. We treated 20 patients with an autistic disorder diagnosed according to DSM-IV, and evaluated the effectiveness. A double blind cross over method was applied in this study because of the small number of patients. Drug effects were observed carefully by the psychologists and pediatric neurologists using an evaluation sheet consisting of twenty items. No significant effectiveness was observed in this study, although four cases (20%) showed some improvement. In conclusion, administration of low dose levodopa to autistic children resulted in no clear clinical improvements of autistic symptoms.

Autistic Disorder↗

PubMed2006

The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms.

OBJECTIVE: To examine psychopathology and influence of intelligence level on psychiatric symptoms in children with the 22q11.2 deletion syndrome (22q11DS). METHOD: Sixty patients, ages 9 through 18 years, were evaluated. Assessments followed standard protocols, including structured and semistructured interviews of parents, videotaped psychiatric interview, and intelligence assessment of the child. Intelligence level, psychiatric symptoms, and classification provided the main outcome. RESULTS: High rates of autism spectrum disorders (30 of 60, 50.0%) and psychotic symptoms (16 of 60, 26.7%) were found in this sample. In 7 of 60 (11.7%), the psychotic symptoms interfered with behavior and caused considerable distress. In these cases, the diagnosis of a psychotic disorder was applied. The average age of the children with psychotic symptoms at time of assessment was 14.2 years. Although it is likely that the high rate of psychopathology in this sample is to some extent associated with the lower level of cognitive function, a major effect of the degree of cognitive impairment on psychiatric morbidity was not found. CONCLUSION: Autism spectrum disorders and subthreshold autistic symptomatology are common in children with 22q11DS. Furthermore, a high rate of psychosis and psychotic symptoms is found in this childhood sample, suggesting an early onset of psychosis in 22q11DS patients. Autistic and psychotic disorders should be considered to be main elements of the behavioral phenotype of 22q11DS children.

Adolescent↗

PubMed2003

Possible association between congenital cytomegalovirus infection and autistic disorder.

We encountered seven children with symptomatic congenital cytomegalovirus (CMV) infection from 1988 to 1995, of whom two (28.6%) developed typical autistic disorder. Case 1: A boy born at 38 weeks' gestation with a birth weight of 3164 g showed generalized petechiae, hepatosplenomegaly, and positive serum CMV-specific IgM antibodies. He was profoundly deaf, mentally retarded, and exhibited a lack of eye contact, stereotyped repetitive play, and hyperactivity. Case 2: A boy delivered at 39 weeks gestation with a birthweight of 2912 g showed non-progressive dilatation of the lateral ventricles observed postnatally. CMV-specific IgM antibodies were positive and CMV-DNA in the urine was confirmed by PCR. The boy was mentally retarded but not deaf. He showed no interest in people and delayed speech development. Subependymal cysts were detected by cranial ultrasound after birth in both patients. This is the first report describing subependymal cysts and the later development of AD. Cranial magnetic resonance imaging revealed an abnormal intensity area in the periventricular white matter suggestive of disturbed myelination; however, no migration disorders were found in our patients. These findings suggest that the timing of injury to the developing brain by CMV may be in the third trimester in some patients with autistic disorder.

Autistic Disorder↗

PubMed2003

Validity of DQ as an estimate of IQ in children with autistic disorder.

The purpose of the present paper was to test the validity of developmental quotients (DQ) on the Mental Development Scale for Infants and Young Children (MDSIYC) as an estimate of intelligence quotient (IQ). Correlations were carried out of its DQ with an IQ on the Japanese version of the Stanford-Binet in 94 children with Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) autistic disorder. With IQ, DQ in the five MDSIYC areas (motor, play, socialization, self-help, and speech) and full-scale DQ (mean of five-area DQ) had significant correlations (Pearson r) of 0.46, 0.56, 0.53, 0.46, 0.85, and 0.68, respectively, suggesting that speech DQ is the most valid estimate of IQ.

Autistic Disorder↗

PubMed1999

[Language in autistic disorders].

Autism is a developmental disorder affecting social relationships, communication and flexibility of thought. These three basic aspects of autism may present in many different forms and degrees. Therefore autism should be considered to be a spectrum of autistic disorders rather than a single strictly defined condition. The spectrum of autistic disorders extends from intelligent individuals with acceptable social integration, to severely retarded patients with scarcely any social interaction. Language is almost always affected either in its formal aspects or in its usage. Autistic linguistic disorders form a specific language disorder (developmental dysphasia) and a pragmatic disorder linked both to the primary language problem and to the social cognitive deficit. We discuss the different linguistic syndromes observed in autistic patients with special emphasis on the semantic-pragmatic disorder.

Asperger Syndrome↗

PubMed2004

Autistic disorder in nineteenth-century London: three case reports.

This article examines the existence, description, perception, treatment, and outcome of symptoms consistent with autistic disorder in nineteenth-century London, England, based on case histories from the notes of Dr William Howship Dickinson at Great Ormond Street Hospital for Children. Three cases meeting the DSM-IV criteria for autistic disorder are described in detail. Other cases in which autistic traits are described are briefly summarized. The article explores the environment of contemporary medical practice, beliefs about childhood brain disorders, and social practice regarding children with brain disorders, and the impact of these factors on assessment and treatment. It correlates Dickinson's observations with current research on autism, providing information about children with autism before the condition was formally named in 1943.

Autistic Disorder↗

PubMed1991

Low field magnetic resonance imaging of the central nervous system in 15 children with autistic disorder.

Fifteen children, 10 boys and 5 girls, with autistic disorder, were studied with low field magnetic resonance imaging (MRI). The age ranged from 2.7-13.1 years, with a mean of 8.3 years. All patients but one (who refused) had a normal CT scan of the C.N.S. The MRI investigation was performed during anaesthesia with a low field magnetic resonance imager. The cerebrum, cerebellum, and brain stem were examined. No pathological changes were found in any of the patients studied.

Adolescent↗

PubMed2007

Assessing the early characteristics of autistic disorder using video analysis.

The behaviours of infants were observed using home videos, in an attempt to identify social difficulties characteristic of infants with autistic disorder. Three groups of infants were analysed: 15 infants who had later been diagnosed with autism, 15 infants who had a developmental or language delay, and 15 typically developing infants. Social behaviours were coded using both quantitative and qualitative measures. The principal discriminating items between the groups were found to be 'peer interest', 'gaze aversion', 'anticipatory postures', and 'proto-declarative showing'. The results suggest that these children later diagnosed with autism are clinically distinct from their peers before the age of two years, and that there are clearly observable behaviours which are important predictors of autistic disorder in pre-verbal children.

Autistic Disorder↗

PubMed2003

[Studies on the adverse effects of fluvoxamine treatment in children with autistic disorder: correlation with genetic polymorphism in serotonin related genes].

Selective serotonin re-uptake inhibitors (SSRIs) have recently been applied to the children with autistic disorder. To create better treatment, we studied here clinical adverse effects of fluvoxamine and correlated them with genetic polymorphism of two genes, the promoter region of serotonin transporter gene (5-HTTLPR) and serotonin 2A receptor gene (5-HT2AR). Twenty-eight subjects, consisting of 23 boys and 5 girls, aged from 3 to 18 years old diagnosed as having autistic disorder were analyzed during fluvoxamine administration. The dosages and duration of fluvoxamine treatment are 1.5 to 3 mg/kg/day and 2 weeks to 17 months (mean 7.9 months), respectively. There were several clinical adverse effects such as sleep disturbance in 9 cases, climb up to high places in 8, gastrointestinal symptoms in 6, hyperactivities in 5, excitement in 4, general fatigability in 2 and urticaria in 1. Medication was discontinued in 2 patients with fatigability and 1 with sleep disturbance, diarrhea and poor appetite. There was no significant correlation between genetic polymorphism in 5-HTTLPR and the occurrence of clinical adverse effects of fluvoxamine. However hyperactivity was significantly more frequent in the subjects with 102T/102T polymorphism of 5-HT2AR, and patients with sleep disturbance were significantly less frequent in the subjects with 102C/102C polymorphism. We conclude that the clinical adverse effects such as climb up to high places and hyperactivity during fluvoxamine treatment may be relatively specific in children, and that genetic polymorphism of 5-HT2AR may be related to the appearance of clinical adverse effects.

Adolescent↗

PubMed2005

Gastrointestinal factors in autistic disorder: a critical review.

Interest in the gastrointestinal (GI) factors of autistic disorder (autism) has developed from descriptions of symptoms such as constipation and diarrhea in autistic children and advanced towards more detailed studies of GI histopathology and treatment modalities. This review attempts to critically and comprehensively analyze the literature as it applies to all aspects of GI factors in autism, including discussion of symptoms, pathology, nutrition, and treatment. While much literature is available on this topic, a dearth of rigorous study was found to validate GI factors specific to children with autism.

Autistic Disorder↗

PubMed1995

Functional deficits in autistic disorder: characterization by technetium-99m-HMPAO and SPECT.

UNLABELLED: Autistic disorder is an early and severe developmental disorder characterized by deficits in verbal and nonverbal language, social skills, cognitive functioning and an abnormal repertoire of behaviors. Current research, however, has failed to identify the neurobiological mechanisms that underlie autism or those cortical brain regions, if any, that are abnormal. METHODS: We examined regional cerebral blood flow (rCBF) in six young, severely autistic patients. High-resolution brain SPECT with 99mTc-HMPAO was performed while five of the six patients were under general anesthesia. The scans reflected the subjects' rCBF in their usual alert behavioral state, since the tracer was injected at least 15 min prior to anesthesia and is rapidly extracted and fixed in the brain. A computer-automated cortical region of interest (ROI) generator was used to define 12 annular cortical regions (region 1 = left frontal, clockwise to region 12 = right frontal) for count data acquisition. The ratio of average counts in each ROI to whole-slice counts for the autistic patients was compared to age-matched controls using repeated measures (splt-plot) ANOVA statistical analysis for three representative brain levels. RESULTS: In the autistic patients, cortical regions 3, 4, and 10 were abnormally low at the cortical level canthomeatal (CM) + 3.5 cm. At level CM + 5.5 cm, regions 3, 4, 5 and 10 were abnormally low, and at level CM + 7.5 cm, regions 7 and 9 were also abnormally low. These regions correspond to abnormally low rCBF values located predominately in the temporal and parietal lobes, with the left cerebral hemisphere showing greater rCBF abnormalities than the right. CONCLUSION: Our findings suggest that the temporal and parietal lobes have abnormal rCBF in autism. HMPAO brain SPECT in combination with general anesthesia is particularly useful for imaging severely noncompliant patients.

Adolescent↗

PubMed1999

Association study of the NF1 gene and autistic disorder.

Neurofibromatosis type 1 (NF1) is increased about 150-fold in autistic patients. The aim of this study was to test for an association between the NF1 locus and autistic disorder. The allele distributions of three markers of the NF1 gene were studied in 85 autistic patients and 90 controls. No differences in allele distributions were observed. However, we found a new allele (allele 5) of the GXAlu marker in four autistic patients. Allele 5 was absent in a larger control population (213 individuals). The patients with allele 5 had a more severe clinical picture, mainly in the fields of motility and tonus. Our preliminary results suggest that the NF1 region is not a major susceptibility locus for autism. However, the GXAlu marker of the NF1 gene appears as a possible candidate for a susceptibility locus in a small subgroup of severely affected autistic patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:729-732, 1999.

Adolescent↗