Lennart von Wendt

Analysis of four neuroligin genes as candidates for autism.

Neuroligins are cell-adhesion molecules located at the postsynaptic side of the synapse. Neuroligins interact with β-neurexins and this interaction is involved in the formation of functional synapses. Mutations in two X-linked neuroligin genes, NLGN3 and NLGN4, have recently been implicated in pathogenesis of autism. The neuroligin gene family consists of five members (NLGN1 at 3q26, NLGN2 at 17p13, NLGN3 at Xq13, NLGN4 at Xp22, and NLGN4Y at Yq11), of which NLGN1 and NLGN3 are located within the best loci observed in our previous genome-wide scan for autism in the Finnish sample. Here, we report a detailed molecular genetic analysis of NLGN1, NLGN3, NLGN4, and NLNG4Y in the Finnish autism sample. Mutation analysis of 30 probands selected from families producing linkage evidence for Xq13 and/or 3q26 loci revealed several polymorphisms, but none of these seemed to be functional. Family-based association analysis in 100 families with autism spectrum disorders yielded only modest associations at NLGN1 (rs1488545, P=0.002), NLGN3 (DXS7132, P=0.014), and NLGN4 (DXS996, P=0.031). We conclude that neuroligin mutations most probably represent rare causes of autism and that it is unlikely that the allelic variants in these genes would be major risk factors for autism.

Search for autism loci by combined analysis of Autism Genetic Resource Exchange and Finnish families

Several genome‐wide screens have been performed in autism spectrum disorders resulting in the identification of numerous putative susceptibility loci. Analyses of pooled primary data should result in an increased sample size and the different study samples have a potential to strengthen the evidence for some earlier identified loci, reveal novel loci, and even to provide information of the general significance of the locus. The objective of this study was to search for potential susceptibility loci for autism, which are supported by two independent samples.

Effectiveness of Melatonin in the Treatment of Sleep Disturbances in Children with Asperger Disorder

Sleep disturbances are common in patients with Asperger disorder. Although these sleep problems are often persistent and may significantly impair the childs daytime well-being, no treatment studies have been reported. In this open clinical trial, the effectiveness of melatonin was studied in a sample of 15 children with Asperger disorder (13 boys, 2 girls) aged 6-17 years using several questionnaires and actigraph measurements. They included assessments of sleep quality, tiredness, and behavior. Melatonin (3 mg/day) was used for 14 days. All the measurements were made three times: before the treatment period, during the treatment (days 12-14), and 3 weeks after the discontinuation of the treatment. The sleep patterns of all the children improved, and half of them displayed excellent responses to melatonin. In particular, actigraphically measured sleep latency decreased from 40.02 +/- 24.09 minutes to 21.82 +/- 9.64 minutes (p = 0.002), whereas sleep duration remained steady at 477.40 +/- 55.56 minutes and 480.48 +/- 50.71 minutes. Despite the short duration of the treatment, behavioral measures also displayed a significant improvement, and most of the effect disappeared after the discontinuation of the melatonin (p = 0.001). In conclusion, melatonin may provide an interesting new and well-tolerated treatment option for children with Asperger disorder suffering from chronic insomnia. However, these results must be confirmed in a controlled study.

Verbal and non-verbal function of children with right- versus left-hemiplegic cerebral palsy of pre- and perinatal origin.

Eighteen children with right‐ and 13 with left‐sided congenital hemiplegia were compared with 19 normal age‐matched controls for verbal and non‐verbal function. CT scans were obtained from 27 of the 31 hemiplegie children. The two hcmiplegic groups were impaired in non‐verbal function compared with controls. The right‐hemiplegic group was more impaired in verbal function than the left‐hemiplegic group and controls; however, impairments were restricted to the girls in the right‐hemiplegic group. The results are discussed in terms of cerebral plasticity and functional reorganisation of cognitive functions after an early unilateral injury. It is argued that girls with left‐hemisphere lesions may be more limited in cerebral plasticity than boys.

IMPROVEMENT OF FUNCTIONAL SITTING POSITION FOR CHILDREN WITH CEREBRAL PALSY

Twenty‐three children with cerebral palsy were photographed and video‐filmed in six different sitting positions—including a hypothetical functional position—and the video‐films and photographs were analysed. It was found that pathological movements were minimised and postural control and arm and hand function best when the child was sitting in a forward‐tipped seat, with a firm backrest supporting the pelvis, arms supported against a table and feet permitted to move backward.

Insomnia is a frequent finding in adults with Asperger syndrome

BackgroundAsperger syndrome (AS) is a neurodevelopmental disorder belonging to autism spectrum disorders with prevalence rate of 0,35% in school-age children. It has been most extensively studied in childhood while there is scarcity of reports concerning adulthood of AS subjects despite the lifelong nature of this syndrome. In children with Asperger syndrome the initiation and continuity of sleep is disturbed because of the neuropsychiatric deficits inherent of AS. It is probable that sleep difficulties are present in adulthood as well. Our hypothesis was that adults with AS suffer from difficulty in initiating and maintaining sleep and nonrestorative sleep (insomnia).Methods20 AS without medication were compared with 10 healthy controls devoid of neuropsychiatric anamnesis. Clinical examination, blood test battery and head MRI excluded confounding somatic illnesses. Structured psychiatric interview for axis-I and axis-II disorders were given to both groups as well as Beck Depression Inventory and Wechsler adult intelligence scale, revised version.Sleep quality was assessed with sleep questionnaire, sleep diary during 6 consecutive days and description of possible sleep problems by the participants own words was requested.Resultscompared with controls and with normative values of good sleep, AS adults had frequent insomnia. In sleep questionnaire 90% (18/20), in sleep diary 75% (15/20) and in free description 85% (17/20) displayed insomnia. There was a substantial psychiatric comorbidity with only 4 AS subject devoid of other axis-I or axis-II disorders besides AS. Also these persons displayed insomnia. It can be noted that the distribution of psychiatric diagnoses in AS subjects was virtually similar to that found among patient with chronic insomnia.Conclusionsthe neuropsychiatric deficits inherent of AS predispose both to insomnia and to anxiety and mood disorders. Therefore a careful assessment of sleep quality should be an integral part of the treatment plan in these individuals. Conversely, when assessing adults with chronic insomnia the possibility of autism spectrum disorders as one of the potential causes of this condition should be kept in mind.

Epidemiology of infantile hydrocephalus in Sweden. II. Origin in infants born at term.

ABSTRACT. The aetiology of infantile hydrocephalus (IH) was studied in a population‐based series of 141 children with IH, born at term in southwestern Sweden 1967–82. A prenatal aetiology was present in 81 children (57%), a pre‐ and perinatal in 6(4%), a perinatal in 27(19%), and a postnatal in 8(6%); the origin in 19 children (13%) remained untraceable. A variety of aetiologies were revealed or indicated among prenatal conditions. The dominant intrauterine infection was toxoplasmosis. The predominant perinatal condition was posthaemorrhagic IH. The broad outline of outcome differed between pathogenetic groups. Children with a clear prenatal onset of IH were found to be at high risk for early death or multiple neurological impairments. Thirteen of 63(21%) within this group had died before 2 years of age and 34 of the 50(68%) survivors showed major neurological dysfunction. This contrasted to the incidences of 3% deaths and 30% sequelae in children with IH of other onset.

Language abilities of children with Asperger syndrome.

Current diagnostic taxonomies (ICD-10, DSM-IV) emphasize normal acquisition of language in Asperger syndrome (AS). Although many linguistic sub-skills may be fairly normal in AS there are also contradictory findings. There are only few studies examining language skills of children with AS in detail. The aim of this study was to study language performance in children with AS and their age, sex and IQ matched controls. Children with AS had significantly lower scores in the subtest of Comprehension of Instructions. Results showed that although many linguistic skills may develop normally, comprehension of language may be affected in children with AS. The results suggest that receptive language processes should be studied in detail in children with AS.

Auditory cortical change detection in adults with Asperger syndrome.

The present study investigated whether auditory deficits reported in children with Asperger syndrome (AS) are also present in adulthood. To this end, event-related potentials (ERPs) were recorded from adults with AS for duration, pitch, and phonetic changes in vowels, and for acoustically matched non-speech stimuli. These subjects had enhanced mismatch negativity (MMN) amplitudes particularly for pitch and duration deviants, indicating enhanced sound-discrimination abilities. Furthermore, as reflected by the P3a, their involuntary orienting was enhanced for changes in non-speech sounds, but tended to be deficient for changes in speech sounds. The results are consistent with those reported earlier in children with AS, except for the duration-MMN, which was diminished in children and enhanced in adults.

Sleep in Young Adults with Asperger Syndrome

Asperger syndrome (AS) is a neurodevelopmental disorder belonging to autism spectrum disorders. Both children and adults with AS have subjective impairment in the initiation and continuity of sleep, and studies using objective assessment are sparse. Twenty young AS adults with frequent complaints of low sleep quality were compared to 10 age-, gender- and education-matched controls without sleep complaints using polysomnography and spectral power analysis of slow-wave sleep. AS subjects displayed a similar polysomnographic profile as compared with controls. In spectral power analysis, a statistically nonsignificant trend towards decreased relative delta power and increased theta power in slow-wave sleep was found in the AS group. It seems that nonorganic insomnia, due to anxiety inherent in AS, is responsible for the low sleep quality in these subjects.