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Pre-attentive auditory sensory processing in autistic spectrum disorder. Are electromagnetic measurements telling us a coherent story?

Sensory processing is a crucial underpinning of the development of social cognition, a function which is compromised in variable degree in patients with pervasive developmental disorders (PDD). In this manuscript, we review some of the most recent and relevant contributions, which have looked at auditory sensory processing derangement in PDD. The variability in the clinical characteristics of the samples studied so far, in terms of severity of the associated cognitive deficits and associated limited compliance, underlying aetiology and demographic features makes a univocal interpretation arduous. We hypothesise that, in patients with severe mental deficits, the presence of impaired auditory sensory memory as expressed by the mismatch negativity could be a non-specific indicator of more diffuse cortical deficits rather than causally related to the clinical symptomatology. More consistent findings seem to emerge from studies on less severely impaired patients, in whom increased pitch perception has been interpreted as an indicator of increased local processing, probably as compensatory mechanism for the lack of global processing (central coherence). This latter hypothesis seems extremely attractive and future trials in larger cohorts of patients, possibly standardising the characteristics of the stimuli are a much-needed development. Finally, specificity of the role of the auditory derangement as opposed to other sensory channels needs to be assessed more systematically using multimodal stimuli in the same patient group.

Attention↗

Effect of fluoxetine on regional cerebral metabolism in autistic spectrum disorders: a pilot study.

The regional metabolic effects of fluoxetine were examined in patients with autism spectrum disorders. Six adult patients with DSM-IV and Autism Diagnostic Interview (ADI) diagnoses of autism (n = 5) and Asperger's syndrome (n = 1), entered a 16-wk placebo-controlled cross-over trial of fluoxetine. The patients received (18)F-deoxyglucose positron emission tomography with co-registered magnetic resonance imaging at baseline and at the end of the period of fluoxetine administration. After treatment, the patients showed significant improvement on the scores of the Yale--Brown Obsessive--Compulsive Scale -- Obsessions subscale and the Hamilton Anxiety Scale; Clinical Global Impressions -- Autism scores showed 3 of the patients much improved and 3 unchanged. Relative metabolic rates were significantly higher in the right frontal lobe following fluoxetine, especially in the anterior cingulate gyrus and the orbitofrontal cortex. Patients with higher metabolic rates in the medial frontal region and anterior cingulate when unmedicated were more likely to respond favourably to fluoxetine. These results are consistent with those in depression indicating that higher cingulate gyrus metabolic rates at baseline predict SRI response.

Adult↗

Use of complementary and alternative treatments for children with autistic spectrum disorders is increasing.

Interventions considered to be CAM are in constant flux. New treatments emerge, older treatments become less popular, and the cycle recurs. Data supporting new treatments should be scrutinized for scientific study design, clinical safety, and scientific validity. Many families approach the clinician armed with brochures, handouts, and printouts from Web sites that are dedicated to the care and support of parents and children with ASD. A recent web search using "autism and detoxification" resulted in almost 8,000 sites. The Defeat Autism Now! (DAN!) Project arose in 1995 from collaboration of members of the Autism Research Institute. The DAN! Project advocates a specific and extensive protocol for diagnosis and treatment and can be viewed at http://www.autism.com/ari/#dan. The scientific validation and support for many interventions is incomplete and disparate from the recommendation in the American Academy of Pediatrics Policy Statement. Families should be encouraged to discuss all proposed investigations or treatments they wish to try with their primary care provider so the practitioner can serve as the medical home (Sidebar, page 688). The clinician should communicate and collaborate with the family and educational professionals to encourage objective identification of what works. With increasing access to health information and societal pressure for families to actively participate in their health management, continued growth of interest in CAM can be anticipated. Clinicians must remember that parents may have different beliefs regarding the effectiveness of treatment and different tolerance for treatment risks. Practitioners must keep avenues of communication open, remain open-minded, and not assume a "don't ask, don't tell" posture in the context of providing a medical home to the increasing number of children diagnosed with autism.

Autistic Disorder↗

Essential fatty acids and phospholipase A2 in autistic spectrum disorders.

A health questionnaire based on parental observations of clinical signs of fatty acid deficiency (FAD) showed that patients with autism and Asperger's syndrome (ASP) had significantly higher FAD scores (6.34+/-4.37 and 7.64+/-6.20, respectively) compared to controls (1.78+/-1.68). Patients with regressive autism had significantly higher percentages of 18:0,18:2n-6 and total saturates in their RBC membranes compared to controls, while 24:0, 22:5n-6, 24:1 and the 20:4n-6/20:5n-3 ratio were significantly higher in both regressive autism and ASP groups compared to controls. By comparison, the 18:1n-9 and 20:4n-6 values were significantly lower in patients with regressive autism compared to controls while 22:5n-3, total n-3 and total dimethyl acetals were significantly lower in both regressive autism and ASP groups compared to controls. Storage of RBC at -20 degrees C for 6 weeks resulted in significant reductions in highly unsaturated fatty acid levels in polar lipids of patients with regressive autism, compared to patients with classical autism or ASP, or controls. Patients diagnosed with both autism and ASP showed significantly increased levels of EPA ( approximately 200%) and DHA ( approximately 40%), and significantly reduced levels of ARA ( approximately 20%), 20:3n-6 and ARA/EPA ratio in their RBC polar lipids, when supplemented with EPA-rich fish oils, compared to controls and non-supplemented patients with autism. Patients with both regressive autism and classical autism/Asperger's syndrome had significantly higher concentrations of RBC type IV phospholipase A2 compared to controls. However, patients with autism/ASP, who had taken EPA supplements, had significantly reduced PLA2 concentrations compared to unsupplemented patients with classical autism or ASP.

Asperger Syndrome↗

Children with autistic spectrum disorders. I: comparison of placebo and single dose of human synthetic secretin.

AIMS: To examine the effect of a single dose of human synthetic secretin (HSS) on behaviour and communication in children with autism spectrum disorder (ASD) using an objective measure of communication and social reciprocity and standardised rating scales. METHODS: Randomised, crossover, double blind, and placebo controlled trial of a single intravenous dose of human synthetic secretin (HSS) 2 CU/kg. The 62 subjects (3-8 years) were assigned to group 1 (saline placebo/HSS) or group 2 (HSS/saline placebo). Diagnosis was confirmed by ADI-R (Autism Diagnostic Interview-Revised) algorithm. Severity of symptoms was rated using the CARS (Childhood Autism Rating Scale). Outcome measures included Communication and Symbolic Behavior Scale (CSBS), Ritvo Real-life Rating Scale, weekly Global Rating Scale (GBRS) by parents and teachers, and daily log of gastrointestinal symptoms. The communication subscale of the CSBS, specifying communication function, reciprocity, and social-affective signalling was videotaped and scored by a blinded, trained observer. RESULTS: Sixty one children completed the study. After randomisation, there were no significant differences in gender, race, age, and parent and teacher GBRS and Ritvo Scale between the two groups. Compared with placebo, secretin treatment was not associated with significant improvement of CSBS standard scores from baseline to 2 or 4 weeks post-infusion. Five children showed clinical improvement in standard scores: two after HSS and three after placebo. There were no significant changes in gastrointestinal symptoms after HSS or saline placebo. CONCLUSIONS: A single dose of intravenous human secretin is not effective in changing behaviour and communication in children with ASD when compared to placebo.

Autistic Disorder↗

Risperidone in preschool children with autistic spectrum disorders: an investigation of safety and efficacy.

INTRODUCTION: Early intervention in autism spectrum disorders (ASDs) appears promising and may represent a window of opportunity for more effective treatment. Whereas the safety and efficacy of risperidone have been established for children aged 5 and older, they has not been adequately tested in preschool children. METHODS: A randomized placebo-controlled study of risperidone in preschool children was conducted in a sample of young children, most of whom were also undergoing intensive behavioral treatment. RESULTS: Preschool children tolerated low-dose risperidone well with no serious adverse effects observed over a 6-month treatment period. Weight gain and hypersalivation were the most common side effects reported, and hyperprolactinemia without lactation or related signs was observed. Significant differences between groups found at baseline complicated the analyses; however, controlling for some of these differences revealed that preschoolers on risperidone demonstrated greater improvements in autism severity. The change in autism severity scores from baseline to 6-month follow up for the risperidone group was 8% compared to 3% for the placebo group. Notably, both groups significantly improved over the 6-month treatment period. CONCLUSIONS: Study findings suggest that risperidone is well tolerated in preschoolers over a 6-month period, but that only minimally greater improvement in target symptoms was evident in the risperidone group, possibly due to the differences between groups at baseline or due to the small sample size. Although these findings are not sufficient to direct treatment, they suggest that larger-scale, double-blind, placebo-controlled investigations of risperidone in preschoolers with ASDs should now be conducted.

Antipsychotic Agents↗

Pharmacotherapy of target symptoms in autistic spectrum disorders.

There are no aetiologically-based treatments available to cure autism. Though psychotropics have a role in the management of some symptoms of autism, clinical trial evidence for the use of psychotropics is in its infancy and needs close monitoring. About half of the subjects with high functioning pervasive developmental disorders (PDDs) are currently reported to be on psychotropics (anti-depressants, stimulants and antipsychotics), with many of them being on anti-epileptic medication simultaneously. Despite this high level of psychotropic use, few studies exist investigating the pharmacokinetics, pharmacodynamics or side-effect profiles in this population. Multiprofessional and parent partnership is essential in managing autism and psychopharmacology should be used in conjunction with environmental manipulation, educational modification and/or behavioral management strategies. A symptomatic approach to managing the difficult behaviours associated with autism is recommended. Some symptoms of autism may be medication responsive (hyperactivity, obsessions, rituals, inattention, tics, etc), while other symptoms may be responsive to behavioural interventions, but may require medication (aggression, anxiety, depression, impulsivity, sleep difficulties, etc), and symptoms which need specific skill remediation are usually non-responsive to medication (deficits in academic, social or sport domains). The new atypical antipsychotics (such as risperidone, olanzapine, amisulpiride, quetiapine) and SSRIs are increasingly being used in autism, with encouraging results, but a risk-benefit ratio of pharmacotherapy is essential with due weight being given to the side-effects of medication. Despite symptomatic improvement with medication, one should remain cautious about long-term use of psychotropics. It is also important to recognize that psychotropics can sometimes worsen behaviour, and can produce iatrogenic symptoms. Certain anti-epileptic medication and psychotropic drugs are metabolized by the same cytochrome P450 isoenzymes in the liver. In such circumstances, the addition of a psychotropic agent may drastically alter the levels of the anti-epileptic medication and vice versa. It is suggested that specialist clinics should be involved when one is considering complex medication regimes, experimental drugs, polypharmacy, or if patients show unusual side-effects or is drug resistant.

Adolescent↗

[Best practice guidelines for the early detection of Autistic Spectrum Disorders (I)].

INTRODUCTION: The interest in early detection of Autism Spectrum Disorders (ASD) lies in the accumulated evidence of the fact that an early customized intervention for children with an ASD and their families leads to an improvement of the child's prognosis in most cases. OBJECTIVE: To establish criteria and procedures for early identification of children at risk of ASD and to facilitate full diagnostic assessment and prompt referral leading to adequate support. Early detection of ASD is extremely important, since early specific individualized treatment for the child and his or her family leads to long-term improvement in many children' prognosis. DEVELOPMENT: Firstly, a critical appraisal of the situation of early detection of ASD in Spain is made after reviewing the scarce bibliography available on current screening and diagnostic practices in the country. Data generated by questionnaires received from 646 Spanish families is also taken into account. Secondly, the Study Group of the Instituto de Salud Carlos III recommends the screening and early diagnosis process to be followed, describing the necessary steps, the public services involved and the available screening and diagnostic tools. CONCLUSIONS: The Study Group draws the main conclusions regarding the situation of ASD early detection in Spain, and makes a consensus proposal for the detection procedures, including routine developmental surveillance and identification of children at risk for ASD by using sensitive and specific assessment tools.

Child↗

[Early detection of autism in children. Review of literature].

The difficulties with early detection of autistic disorder in children are discussed. DSM-IV diagnostic criteria are presented. Usefulness of clinical interview and clinical experiment in diagnosing autistic disorder are analyzed.

Age Factors↗

Patterns of development in young children with autism.

OBJECTIVE: To determine the extent to which the developmental profile of children less than 4 years can help in distinguishing children with autism from children with developmental delay. METHODS: Subjects were 32 children with autism as per the DSM IV criteria and 32 children with developmental delay matched on chronological and academic age. The Developmental Profile II was used to assess the developmental functioning in five domains including physical, social, self help, academic, and communication. RESULTS: The two groups showed significantly different developmental profiles and these differences were accounted for mainly by significantly lower social skills and superior motor skills in the autistic group as compared to the developmentally delayed group. CONCLUSION: Developmental Profile II may help in distinguishing young children with autistic disorder from non-autistic children with comparable developmental delays.

Autistic Disorder↗

Multisite, double-blind, placebo-controlled trial of porcine secretin in autism.

OBJECTIVE: To examine the efficacy of intravenous porcine secretin for the treatment of autistic disorder. METHOD: Randomized, double-blind, placebo-controlled, crossover design. Fifty-six subjects with autistic disorder received either a secretin or placebo infusion at baseline and the other substance at week 4. Subjects were given the Autism Diagnostic Observation Schedule (ADOS) and other pertinent developmental measures at baseline and at weeks 4 and 8 to assess drug effects. RESULTS: For the primary efficacy analysis, change of ADOS social-communication total score from week 0 to week 4, no statistically significant difference was obtained between placebo (-0.8 +/- 2.9) and secretin groups (-0.6 +/- 1.4; t54 = 0.346, p < .73). The other measures showed no treatment effect for secretin compared with placebo. CONCLUSION: There was no evidence for efficacy of secretin in this randomized, placebo-controlled, double-blind trial.

Autistic Disorder↗

[Reading mind from pictures of eyes: theory of mind, language ability, general intellectual ability, and autism].

Some researchers have claimed that theory of mind or 'mind reading' ability, necessary for inferring the mental states of others, depends on language ability. However, previous tests of theory of mind were verbally demanding, and high correlations found might have been an artifact. This paper reports the performance of 22 children with autism, with varying degrees of dysfunction, on a test devised by Baron-Cohen, Jolliffe, Mortimore, and Robertson (1997), based on a relatively nonverbal theory of mind. The test involved inference of mental states from photographs of human eyes. Results indicated that mind reading ability was independent of language ability, general intelligence, or mental age. Test scores were, however, strongly related to the severity of autistic disorder. These results suggest both the independence of mind-reading ability from language ability and general intelligence, and a strong relationship between theory of mind deficit and the autistic disorder.

Autistic Disorder↗

Using self-report to identify the broad phenotype in parents of children with autistic spectrum disorders: a study using the Autism-Spectrum Quotient.

BACKGROUND: The concept of the 'broad phenotype' of autism refers to the finding that relatives of people with autism often have mild forms of autistic-like characteristics, such as social and communicative difficulties. This study used the Autism Spectrum Quotient (AQ), a questionnaire devised to assess features of the broad phenotype in adults, with parents of people with autism, to see whether they would be more likely to obtain extreme scores than a control group. METHODS: The AQ was administered to parents of 69 people with an autism spectrum disorder and parents of 52 controls. RESULTS: On two of the five subscales of the AQ, social skills and communication, parents of people with autism obtained higher scores than control parents. The other three scales, attention to detail, attention switching, and imagination, did not differentiate groups. The correlation between social skills and communication scales was .663. The scales can be combined to give an index of broad phenotype. CONCLUSIONS: The AQ appears to be sensitive to the broad phenotype, provided attention is restricted to the social skills and communication scales.

Adult↗

Dental care of autistic children within the non-specialized Public Dental Service.

Children with an autistic disorder may need more dental care and may also be more difficult to treat than healthy children. This study compared oral health in autistic and healthy children. Also explored was the dental management of autistic children within the non-specialized Public Dental Service. The study was designed as a case-control study with all cases of autistic disorders aged 3-19 years identified within a primary care area in southwest Sweden. One dentist did a clinical investigation of cases and one control per case. The patients, or their parents, answered a questionnaire. 28 patients were identified and 20 (71%) agreed to participate in the study. Cases and controls had a similar prevalence of fillings, caries, gingivitis and degree of oral hygiene. However, the need of orthodontic treatment seemed to be greater among the autistic children. According to a standardised assessment, autistic children were less able to cooperate in the dental treatment. Approximately 30% of the cases had occasionally been subjected to specialized dental care. The results of this study indicate that the care provided to autistic children within the non-specialized Public Dental Service is satisfactory, provided that there is access to a paediatric dentist when necessary.

Adolescent↗

On doing the "impossible": inferring that a putative causal relationship does not exist.

A simple heuristic is proposed for drawing a warranted inference that a causal relationship does not exist between two events. It is illustrated by a study of the putative indirect causal relationship between Autistic Disorder and the Fragile X syndrome. This study was designed to ensure that a failure to find such a relationship provided good reasons for concluding that it was unlikely there was a relationship between Autistic Disorder and the Fragile X syndrome.

Autistic Disorder↗

Behavioral intervention for children with autism.

TOPIC: Autistic disorder is a pervasive developmental disorder characterized by deviant social interaction, communication, and behavior. It is a lifelong disability that affects 2-5/10,000 individuals. Children with autistic disorder are increasingly present in all patient care settings. Their behavior is often mystifying and overwhelming to professionals. PURPOSE: To offer specific information about appropriate intervention strategies that can be applied to impatient units, schools, community residences, and homes. SOURCES: Published information and clinical experience. CONCLUSIONS: Behavioral treatment methods provide guidance for the treatment of children with autism. However, they must be adapted to each child's specific circumstances. Additional research is needed to refine current behavioral treatment approaches.

Autistic Disorder↗

Autism under age 3 years: a clinical study of 28 cases referred for autistic symptoms in infancy.

Twenty-eight children referred with a preliminary diagnosis of autistic disorder under age 3 yrs were extensively examined from the neuropsychiatric point of view and followed up for several months to several years. A diagnosis of autistic disorder was confirmed in 75% of the cases. A variety of associated medical conditions was identified. It was concluded that autism can be diagnosed in a substantial proportion of cases before age 3 yrs and that the neurobiological background is similar to that seen in older autistic children.

Autistic Disorder↗

Autism in immigrants: children born in Sweden to mothers born in Uganda.

Three boys diagnosed as suffering from autistic disorder were born in Sweden to mothers born in Uganda. Two were related but the third boy was unrelated to the others. The prevalence for autistic disorder in Göteborg children born to mothers who were born in Uganda was 15% which is almost 200 times higher than in the general population of children. The possible reason for the high autism rate in this particular ethnic subgroup is discussed.

Autistic Disorder↗