Multiple doses of secretin in the treatment of autism: a controlled study.

UNLABELLED: Dramatic effects on autistic behaviour after repeated injections of the gastrointestinal hormone secretin have been referred in a number of case reports. In the absence of curative and effective treatments for this disabling condition, this information has created new hope among parents. Although controlled studies on the effect of mainly one single dose have not documented any effect, many children still continue to receive secretin. Six children enrolled in a double-blind, placebo-controlled crossover study in which each child was its own control. Human synthetic secretin, mean dose 3.4 clinical units, and placebo were administered intravenously in randomized order every 4th wk, on three occasions each. The measurement instruments were the visual analogue scale (VAS) and the aberrant behaviour checklist (ABC). Statistically significant differences were found for placebo in 3 out of 6 children and for secretin in one child, using parental ratings only (VAS scores). Differences were small and lacked clinical significance, which was in accordance with the overall impression of the parents and teachers and visual inspection of graphs. CONCLUSION: In this placebo-controlled study, multiple doses of secretin did not produce any symptomatic improvement.

Y chromosome haplogroups in autistic subjects.

The male to female ratio in autism is 4:1 in the global autistic population, but increases to 23:1 in autistic subjects without physical or brain abnormalities.(1) Despite this well-recognised gender difference, male predisposition to autistic disorder remains unexplained and the role of sex chromosomes is still debated. Numerical and structural abnormalities of the sex chromosomes are among the most frequently reported chromosomal disorders associated with autism. However, genome scans have failed to detect linkage on the X chromosome(2,3,4) and this approach cannot study the non-recombining region of the Y chromosome. In this study, we searched for a specific Y chromosome effect in autistic subjects. Using informative Y-polymorphic markers, the Y chromosome haplotypes of 111 autistic subjects from France, Sweden and Norway were defined and compared with relevant control populations. No significant difference in Y-haplotype distribution between the affected and control groups was observed. Although this study cannot exclude the presence of a Y susceptibility gene, our results are not suggestive of a Y chromosome effect in autism.

Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study.

Family and twin studies have suggested a genetic component in autism. We performed a genome-wide screen with 264 microsatellites markers in 51 multiplex families, using non-parametric linkage methods. Families were recruited by a collaborative group including clinicians from Sweden, France, Norway, the USA, Italy, Austria and Belgium. Using two-point and multipoint affected sib-pair analyses, 11 regions gave nominal P -values of 0.05 or lower. Four of these regions overlapped with regions on chromosomes 2q, 7q, 16p and 19p identified by the first genome-wide scan of autism performed by the International Molecular Genetic Study of Autism Consortium. Another of our potential susceptibility regions overlapped with the 15q11-q13 region identified in previous candidate gene studies. Our study revealed six additional regions on chromosomes 4q, 5p, 6q, 10q, 18q and Xp. We found that the most significant multipoint linkage was close to marker D6S283 (maximum lod score = 2.23, P = 0.0013).

Autism and related disorders: epidemiological findings in a Norwegian study using ICD-10 diagnostic criteria.

Recent studies of the prevalence of autism have suggested higher estimates than previously described. Various diagnostic criteria for autism and related disorders have been applied, with variability in case finding methodology and characteristics of populations as well. In this study, maternal and child health clinics covering 98% of the population were used for screening pervasive developmental disorders. Extensive medical investigation was carried out on the majority of cases. In this Norwegian population of children ages 3-14 years the minimum prevalence estimate for childhood autism was 4-5 per 10,000 using ICD-10 research criteria, and did not confirm the high estimates suggested more recently. Medical disorders identified were associated with mental retardation rather than specifically with autism.

[Depression and Down syndrome]. / Depresjon og Downs syndrom.

Emotional and behavioural disorders are frequent complications of mental retardation that often go unrecognised or untreated. We describe a 13-year old girl with Down's syndrome and depressive illness who responded well to paroxetin. The importance of organizing comprehensive health provision for children with mental retardation in a way that focuses both psychiatric and physical illness is emphasised.

Childhood autism: the need for physical investigations.

In this paper the results of an extensive medical investigation of 25 children with childhood autism are presented and compared with those found in a group of non-autistic individuals matched for sex, age and intellectual level, all referred for developmental deviancy of unknown etiology. The examination included a psychiatric assessment and a neurological examination in addition to neurophysiological, chromosomal, metabolic and neuroimaging evaluation. In the clinical examination macrocephaly was found only among the autistic individuals, while the frequency of pathological cerebral CT and clinical parameters such as tendon reflexes and mobility problems was significantly greater in the control group. All the other pathological findings were found to occur with the same frequency in the two groups. Except for research purposes this study did not lend support to those who argue for extensive medical examinations for all children with autism. Based on the present findings, ordinary procedures for assessment of developmentally delayed children should be followed. This should include a systematic clinical neuropaediatric examination, an assessment of vision and hearing and a chromosome study, including that for fragile X.

Changing criteria of autistic disorders: a comparison of the ICD-10 research criteria and DSM-IV with DSM-III-R, CARS, and ABC.

Revised versions of diagnostic manuals, the International Classification of Diseases (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) all operate with several subgroups in the autistic spectrum. Five of the subgroups are identical in the two manuals, but ICD-10 contains five in addition. 132 children were diagnosed using ICD-10, DSM-IV, DSM-III-R, the Childhood Autism Rating Scale (CARS), and the Autistic Behavior Checklist (ABC). Five out of ten alternative subgroups of Pervasive Developmental Disorders (PDD) were identified in a population of developmentally impaired children. These subgroups were the same in the two manuals; the additional ones in ICD-10 were not identified. With the exception of the groups Disintegrative Disorder and Rett syndrome, significant differences were found between all the subgroups within the PDD spectrum and between the PDD group and the non-PDD group. Some problems connected with the guidelines in the ICD-10 manual are discussed.

Gangliosides in children with autism.

Concentrations of the four major brain gangliosides, GM1, GD1a, GD1b and GT1b, biochemical markers of neuronal membranes, were determined in the cerebrospinal fluid (CSF) of 20 children with autism and in 25 controls. In addition, the gangliosides were determined in children with different forms of non-progressive neurological disorders lacking clinical features of autism. GM1, GD1a, GD1b and GT1b were significantly increased in patients with autism compared with age-matched controls and children with non-progressive neurological disorders. The gangliosides have previously been shown to have a function in synaptic transmission and increased synaptic activity leads to added release of gangliosides. Our finding of increased CSF levels of gangliosides in autism suggests increased synaptic activity in this disorder.

[Asperger's syndrome]. / Aspergers syndrom.

In the revised diagnostic systems ICD-10 and DSM-IV Asperger's syndrome is listed as a subgroup under Pervasive developmental disorders. It has been argued that persons with this syndrome have similar characteristics as high functioning autists. The knowledge now available about autism is useful for understanding Asperger's syndrome, also when it comes to treatment strategies. The authors discuss differential diagnoses and assessment programmes.

[Gluten-free diet in infantile autism. A therapeutic trial]. / Glutenfri diett ved infantil autisme. Et behandlingsforsøk.

It has been postulated that there may be a connection between wheat-gluten/milk-casein and mental disorders such as schizophrenia, hyperactivity and autism. In this study seven patients with infantile autism, three before puberty and four after puberty, were given a gluten-free diet. Three children were provoked with gluten/placebo in a double-blind study. Four young patients participated in an open study and were given a gluten-free diet in six months. Behaviour was registered before, during and after the period with a gluten-free diet. Visual Analogue Scale and Real Life Rating Scale were used to register changes in behaviour. No connection was observed between gluten and behaviour typical for these patients. On the contrary, the gluten-free diet seemed to be another negative factor leading to further social isolation in this group of highly socially handicapped patients and families.