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Naltrexone in young autistic children: replication study and learning measures.

OBJECTIVE: This study expanded upon previous work on naltrexone efficacy and safety in young autistic children and assessed performance on learning measures. METHOD: Eleven children with autistic disorder, aged 3.0 to 8.3 years, were studied in home, school, and outpatient laboratory, bringing to 24 the combined study sample. Naltrexone, 1.0 mg/kg, was given daily in a randomized, double-blind, crossover design. Dependent measures were parent and teacher Clinical Global Impressions (CGI) and Naltrexone Side Effects Rating Scale (SE), Conners Parent Impulsivity/Hyperactivity Factor, Teacher Hyperactivity Factor, laboratory CGI, and analysis of videotaped behavior. Learning measures were the Early Intervention Developmental Profile-Language and paired-associate learning. RESULTS: Comparisons between naltrexone and baseline, but not naltrexone and placebo, on parent and teacher ratings showed statistical significance. Three of 11 subjects improved in two or more settings. Side effects were mild. Administering naltrexone was a challenge. The combined study sample showed improvement on all parent measures and on Teacher CGI and SE-Restlessness compared with baseline and placebo. Eleven of the 24 children improved in two or more settings. Scores on learning measures did not change across conditions. CONCLUSIONS: Naltrexone was associated with modest improvement of behavior in 11 of 24 children, but learning did not improve.

Attention↗

Catatonia and autistic spectrum disorders.

The phenomenon of catatonic-like states in people with autistic spectrum disorders is discussed in the context of current knowledge about catatonia as it occurs in severe mental illness and, less frequently documented, in conjunction with developmental disorders. The existing literature on catatonic-like states in people with autistic spectrum disorders is summarized, and it is suggested that such states are not directly comparable with the existing concepts of catatonia. A concept of 'autistic catatonia' is outlined in terms of both its phenomenology and its possible aetiological and maintaining factors. A case study is presented that examines this phenomenon from a cognitive neuropsychological perspective, together with implications for everyday management. The implications of this work for both research and clinical practice are discussed.

Adolescent↗

Autistic-spectrum disorders in Down syndrome: further delineation and distinction from other behavioral abnormalities.

The present study extends our previous work characterizing the behavioral features of autistic-spectrum disorder (ASD) in Down syndrome (DS) using the Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AutBehav). We examined which specific behaviors distinguished the behavioral phenotype of DS + ASD from other aberrant behavior disorders in DS, by determining the relative contribution of ABC and AutBehav subscales and items to the diagnosis of ASD. A total of 127 subjects (aged 2-24 years; mean age: 8.4 years; approximately 70% male), comprising: a cohort of 64 children and adolescents with DS and co-morbid ASD (DS + ASD), 19 with DS and stereotypic movement disorder (DS + SMD), 18 with DS and disruptive behaviors (DS + DB), and 26 with DS and no co-morbid behavior disorders (DS + none) were examined using the aforementioned measures of aberrant behavior. We found that subjects with DS + ASD showed the most severe aberrant behavior, especially stereotypy compared to DS + none and lethargy/social withdrawal and relating problems compared to DS + SMD. Specifically, relatively simple stereotypic behavior differentiated DS + ASD from DS + DB, whereas odd/bizarre stereotypic and anxious behavior characterized DS + ASD relative to DS + SMD and DS + none. Additionally, in a subset of subjects with DS + ASD and anxiety, social withdrawal was particularly pronounced. Overall, our findings indicate that a diagnosis of DS + ASD represents a distinctive set of aberrant behaviors marked by characteristic odd/bizarre stereotypic behavior, anxiety, and social withdrawal.

Adolescent↗

5-HTTLPR variants not associated with autistic spectrum disorders.

To determine whether there is an association of polymorphic variants of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) and autistic spectrum disorders, we analyzed the 5-HTTLPR genotypes of 72 autistic subjects, 11 fragile X syndrome patients with autistic behavior, 43 normal subjects, and 49 fragile X syndrome non-autistic subjects. The distribution frequency of 5-HTTLPR long allele (L) and the short allele (S) variants showed no differences between subjects. Our findings do not support the hypothesis that polymorphic 5-HTTLPR variants are a susceptibility factor for autistic disorders.

Alleles↗

Prevalence of autistic spectrum disorder in children attending mainstream schools in a Welsh education authority.

All mainstream primary schools in Cardiff were invited in July 1998 to participate in a prevalence survey of autistic spectrum disorder. Teachers of each class filled in a questionnaire based on ICD-10 criteria for autistic disorders. The Autism Spectrum Screening Questionnaire (ASSQ) was completed on children identified with problems identified by the questionnaire. A total of 11692 children born between 1 September 1986 and 31 August 1990 were screened: 234 (2%) children were identified as requiring an ASSQ; 151 of 234 (65%) ASSQs were returned. Of the 151, 60 children (52 male, 8 female; 40%) scored 22 or more. Their notes and the involved professionals were consulted. Thirty-five children, unknown to specialist services or with complex features, required additional assessment. Seventeen children (all male) were found to be on the autistic spectrum. When the overall rubric was disentangled we found a diverse population of affected children including a handful who did not fit easily into ICD-10 classification. Correcting for incomplete ascertainment we found a minimum prevalence of 20.2 out of every 10 000 (SE = 4.5) for autistic spectrum disorder in this population.

Age Factors↗

Comorbidity of autistic spectrum disorders in children with Down syndrome.

The aim of the study was to identify the comorbidity of autistic spectrum disorders in a population of children with Down syndrome (DS). All children with DS within a defined population of South Birmingham were identified. The Asperger Syndrome Screening Questionnaire and the Child Autism Rating Scale were completed and diagnosis made according to ICD-10 criteria following interview and observation. Thirty-three of 58 identified children completed the measures, four of whom received a diagnosis of an autistic spectrum disorder. This is equivalent to a minimum comorbid rate of 7%. The questionnaire items concerning social withdrawal, restricted or repetitive interests, clumsiness, and unusual eye contact were associated with an autistic disorder. Of the remaining 29 participating children, 11 also displayed marked obsessional and ritualistic behaviours. The comorbid occurrence of autism and DS is at least 7%. It is important that these children are identified and receive appropriate education and support. A full assessment of social, language, and communication skills and behaviour is crucial, particularly in children with DS who appear different from other children with DS. Potential mechanisms accounting for this comorbidity are discussed.

Adolescent↗

Fluorine magnetic resonance spectroscopy measurement of brain fluvoxamine and fluoxetine in pediatric patients treated for pervasive developmental disorders.

OBJECTIVE: Pediatric populations, including those with autistic disorder or other pervasive developmental disorders, increasingly are being prescribed selective serotonin reuptake inhibitors (SSRIs). Little is known about the age-related brain pharmacokinetics of SSRIs; there is a lack of data regarding optimal dosing of medications for children. The authors used fluorine magnetic resonance spectroscopy ((19)F MRS) to evaluate age effects on whole-brain concentrations of fluvoxamine and fluoxetine in children taking SSRIs. METHOD: Twenty-one pediatric subjects with diagnoses of autistic disorder or other pervasive developmental disorders, 6-15 years old and stabilized with a consistent dose of fluvoxamine or fluoxetine, were recruited for the study; 16 successfully completed the imaging protocol. Whole-brain drug levels in this group were compared to similarly acquired data from 28 adults. RESULTS: A significant relationship between dose and brain drug concentration was observed for both drugs across the age range studied. Brain fluvoxamine concentration in the children was lower, consistent with a lower dose/body mass drug prescription; when brain concentration was adjusted for dose/mass, age effects were no longer significant. Brain fluoxetine concentration was similar between age groups; no significant age effects on brain fluoxetine drug levels remained after adjustment for dose/mass. Observations of brain fluoxetine bioavailability and elimination half-life also were similar between age groups. CONCLUSIONS: These findings suggest that fluvoxamine or fluoxetine prescriptions adjusted for dose/mass are an acceptable treatment approach for medicating children with autistic disorder or other pervasive developmental disorders. It must be determined whether these findings can be generalized to other pediatric populations.

Adolescent↗

Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement.

One hundred and twenty-nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

Autistic Disorder↗

Episodic memory in adults with autistic spectrum disorders: recall for self- versus other-experienced events.

People with autistic spectrum disorders (ASD) have difficulties in recalling recently experienced events, which is dependent upon intact functioning of several aspects of 'self awareness'. The current study examined impaired episodic recall in ASD and its relationship to specific impairments in aspects of 'self awareness'. Between-group (participants with learning disabilities with and without autistic spectrum disorder) experimental design examining free and cued recall of table-top activities that were either self-experienced by participants or observed being performed by the experimenter. Participants with ASD did not show superiority of free recall for self-experienced events over observed events, nor for recall of other-experienced events over self-experienced events, but did demonstrate a superiority for cued recall of self-experienced events. The implications for theory and practice are discussed.

Adult↗

Autistic spectrum disorders in childhood epilepsy surgery candidates.

One third of children with autistic spectrum disorders (or pervasive developmental disorders) enter that state by regression from a more normal prior development at the onset of epilepsy or epileptiform abnormality in the electroencephalogram. In a very small proportion structural lesions of the temporal lobes are discovered. These form part of the sample of children coming to a surgical treatment programme. Ninety-eight child candidates for epilepsy surgery were seen by one neuropsychiatrist. Their psychiatric diagnoses were coded on DSM IV schedules. Other variables of interest were the age at onset of epilepsy; the nature, the side, and time of acquisition of the lesion; intelligence, and sex. There were 19 children with autistic spectrum disorders including eight with Asperger's syndrome. Ten of the children in the autistic group had right brain lesions; six were dysembryoplastic neuroepithelial tumours (DNETs); two were cortical dysplasias; one tuberous sclerosis; one hemi-cortical defect; and 1 mesial temporal sclerosis. Nine started epilepsy in their first year; nine had IQs in the retarded range; nine of the 11 were male. Six of eight Asperger's children had right brain lesions; two DNETs; four mesial temporal sclerosis; one Rasmussen encephalitis. Four started epilepsy in their first year; one was retarded; five were female. Children who had no, or other, psychiatric disorder also showed "mass" lesions, or temporal sclerosis but with different biases as to side, sex, and very early onset of epilepsy from the autistic spectrum group. Very early onset of epilepsy, with lesions of embryonal origin, in the right temporal lobe, strongly predisposed males towards autistic regression. Such patients should be referred very early for consideration of urgent surgical treatment.

Age of Onset↗

Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children.

Children with autistic spectrum disorders (ASDs) tend to suffer from severe gastrointestinal problems. Such symptoms may be due to a disruption of the indigenous gut flora promoting the overgrowth of potentially pathogenic micro-organisms. The faecal flora of patients with ASDs was studied and compared with those of two control groups (healthy siblings and unrelated healthy children). Faecal bacterial populations were assessed through the use of a culture-independent technique, fluorescence in situ hybridization, using oligonucleotide probes targeting predominant components of the gut flora. The faecal flora of ASD patients contained a higher incidence of the Clostridium histolyticum group (Clostridium clusters I and II) of bacteria than that of healthy children. However, the non-autistic sibling group had an intermediate level of the C. histolyticum group, which was not significantly different from either of the other subject groups. Members of the C. histolyticum group are recognized toxin-producers and may contribute towards gut dysfunction, with their metabolic products also exerting systemic effects. Strategies to reduce clostridial population levels harboured by ASD patients or to improve their gut microflora profile through dietary modulation may help to alleviate gut disorders common in such patients.

Autistic Disorder↗

Elevated plasma gamma-aminobutyric acid (GABA) levels in autistic youngsters: stimulus for a GABA hypothesis of autism.

BACKGROUND: Autistic Disorder is an early-onset developmental disorder with severe lifelong impact on social functioning, communication, and behavior. There is currently no marker or cure. The pathophysiology and etiology are obscure. Evidence for abnormal gamma-aminobutyric acid (GABA) function in Autistic Disorders is limited. A few case-reports and small studies have reported differences in GABA levels in plasma, platelets, and urine, compared to controls. Further studies on abnormalities of GABA function in Autistic Disorder are warranted. MATERIAL/METHODS: Plasma GABA levels were measured using a new and sensitive technique, based on gas chromatography/mass spectrometry, in a small group of youngsters with Autistic Disorder and Attention-Deficit/Hyperactivity Disorder. Participants were outpatients between ages 5-15, satisfying modern criteria for these disorders. RESULTS: Elevated plasma GABA levels were found in youngsters with Autistic Disorder. Psychotropic medications did not seem to affect plasma GABA levels in this study. Plasma GABA levels decreased with age. CONCLUSIONS: Elevated plasma GABA levels may be a biochemical marker of Autistic Disorder. This study supports the hypothesis that GABAergic mechanisms play a role in the etiology or pathophysiology of Autistic Disorder. However, the hypothesis remains unspecified owing to lack of research. Future studies on the clinical associations of seizure disorders, mood disorders, and catatonia in autistic people may provide the necessary data to formulate a coherent theory of GABA dysfunction in Autistic Disorder. More trials of medication with known or suspected effects on GABA function are warranted.

Adolescent↗

Early intervention for infants with autistic spectrum disorders in Japan.

BACKGROUND: To date, many researchers in Japan have assumed that the cause of autistic spectrum disorders is attributable to some disorder in the ability of the child. However, we have been working on the premise that autistic spectrum disorders are brought about by relationship disturbances in early infancy and have been attempting to validate this hypothesis through early intervention. METHODS: We have examined the developmental process of affective communication in infants with autistic spectrum disorders. We have postulated that approach-avoidance motivational conflict (Richer) is the primary factor impeding the development of affective communication and have focused therapeutic intervention on this perspective. RESULTS: As a result, attachment behavior was markedly improved in children, but affective communication with their mothers was not. Examing the mothers' images of themselves in infancy in mother-infant psychotherapy, problems that the mothers had themselves in infacy with attachment behavior to their own mothers affected the mothers' internal representation of their children, leading to active evolution of mother-child interaction and development of affective communication between the mother and child. CONCLUSIONS: In this context, the basis and significance of the internal representation of both parties being determinants in the quality of mother-child communication are discussed. Our goal in early intervention is not the elevation of a child's linguistic-cognitive abilities, but the creation of a comforting relationship in which both parent and child can live securely, without strain.

Autistic Disorder↗

Intervention pilot for parents of children with autistic spectrum disorder.

Parents of children who receive the diagnosis of autistic spectrum disorder (ASD) experience a situational crisis related to receiving the diagnosis, which causes feelings of distress and urgency to access services for the affected child. This paper describes a randomized trial (n = 31) that was conducted at a regional diagnostic center of a large metropolitan children's hospital to (a) refine a nursing intervention designed for parents of children with ASD and (b) to identify methodological revisions for a larger study. A secondary purpose was to test the effects of a post-diagnosis nursing intervention on parents' reports of stress, impact of event (diagnosis), and use of services after a child is newly diagnosed with ASD. The intervention consisted of usual care plus 3 hours contact with a pediatric nurse practitioner (PNP) for counseling, instruction, and assistance with implementation of the recommended treatment plan. The control group received only the usual care post-diagnosis, which consisted of a 1-hour consultation session to receive the results of diagnostic tests and a written copy of the recommended treatment plan provided by a developmental pediatrician and/or PNP. Between group differences in measures of "impact of event" and "perceived stress" were not statistically significant. This was attributed to a small sample size. A larger study is feasible and recommended with an expanded nursing intervention and a significantly larger sample recruited from an additional recruitment site. Nurses working with this special population must recognize that parents have information and counseling needs that begin after they receive the diagnosis of ASD for their child and can address these needs with a standardized nursing intervention.

Adult↗

Neuropsychiatric assessment of children with autism: a population-based study.

Thirty-five children with autistic disorder and 17 with autistic-like conditions underwent an exhaustive neurobiological evaluation, and the findings were contrasted with those obtained from various comparison groups. Almost 90 per cent of the children with autistic disorder and autistic-like conditions had major indications of brain damage or dysfunction. Some of those who did not show such abnormalities had a first-degree relative with Asperger syndrome. The rate of abnormality was similar to that of severely mentally retarded children, but in excess of that of normal children. Within the autism group, abnormality rate did not correlate with degree of mental retardation. It is concluded that autism has multiple biological aetiologies and that autistic symptoms in a child should always prompt a thorough medical/neurobiological evaluation.

Adolescent↗

Motion and form coherence detection in autistic spectrum disorder: Relationship to motor control and 2:4 digit ratio.

Children with autistic spectrum disorder and controls performed tasks of coherent motion and form detection, and motor control. Additionally, the ratio of the 2nd and 4th digits of these children, which is thought to be an indicator of foetal testosterone, was measured. Children in the experimental group were impaired at tasks of motor control, and had lower 2D:4D than controls. There were no group differences in motion or form detection. However a sub-group of children with autism were selectively impaired at motion detection. There were significant relationships between motion coherence detection and motor control in both groups of children, and also between motion detection, fine motor control and 2D:4D in the group of children with autistic spectrum disorder.

Asperger Syndrome↗

[Diagnostic criteria of autism and Asperger's syndrome: similarities and differences].

The American Psychiatric Association's last version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; APA, 1994) identifies within pervasive developmental disorders five subgroups: (a) autistic disorder; (b) Rett's disorder; (c) childhood disintegrative disorder; (d) Asperger's disorder's and (e) pervasive developmental disorder not otherwise specified. However, the diagnosis of the different sub-groups is difficult to establish, particularly between autistic disorder and Asperger's disorder. This article exposes the diagnostic criteria of autism and Asperger's syndrome in order to illustrate the similarities and differences between the two disorders.

Autistic Disorder↗