Brief report: retrospective case series of oxcarbazepine for irritability/agitation symptoms in autism spectrum disorder.

We examined response to oxcarbazepine prescribed for irritability/agitation symptoms in a retrospective case series of 30 patients with Autism Spectrum Disorder (ASD). The average patient was 12.0 years old (range 5-21) and taking two other psychotropic medications (range 0-4). Fourteen patients (47 %) had a clinical global impression of improvement score of 'much improved' during treatment. Ten patients (33 %) showed an improvement on their clinical global impression of severity score. Seven patients (23 %) had a clinically significant adverse event or side effect leading to oxcarbazepine discontinuation. Without a placebo group, it is not possible to evaluate whether oxcarbazepine provides benefit for irritability/agitation symptoms in ASD. The high rate of adverse events suggests its use should be accompanied by caution.

Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors.

The objectives of this study were to characterize gastrointestinal dysfunction (GID) in autism spectrum disorder (ASD), to examine parental reports of GID relative to evaluations by pediatric gastroenterologists, and to explore factors associated with GID in ASD. One hundred twenty-one children were recruited into three groups: co-occurring ASD and GID, ASD without GID, and GID without ASD. A pediatric gastroenterologist evaluated both GID groups. Parents in all three groups completed questionnaires about their child's behavior and GI symptoms, and a dietary journal. Functional constipation was the most common type of GID in children with ASD (85.0%). Parental report of any GID was highly concordant with a clinical diagnosis of any GID (92.1%). Presence of GID in children with ASD was not associated with distinct dietary habits or medication status. Odds of constipation were associated with younger age, increased social impairment, and lack of expressive language (adjusted odds ratio in nonverbal children: 11.98, 95% confidence interval 2.54-56.57). This study validates parental concerns for GID in children with ASD, as parents were sensitive to the existence, although not necessarily the nature, of GID. The strong association between constipation and language impairment highlights the need for vigilance by health-care providers to detect and treat GID in children with ASD. Medications and diet, commonly thought to contribute to GID in ASD, were not associated with GID status. These findings are consistent with a hypothesis that GID in ASD represents pleiotropic expression of genetic risk factors.

Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes.

Supplemental melatonin has shown promise in treating sleep onset insomnia in children with autism spectrum disorders (ASD). Twenty-four children, free of psychotropic medications, completed an open-label dose-escalation study to assess dose-response, tolerability, safety, feasibility of collecting actigraphy data, and ability of outcome measures to detect change during a 14-week intervention. Supplemental melatonin improved sleep latency, as measured by actigraphy, in most children at 1 or 3 mg dosages. It was effective in week 1 of treatment, maintained effects over several months, was well tolerated and safe, and showed improvement in sleep, behavior, and parenting stress. Our findings contribute to the growing literature on supplemental melatonin for insomnia in ASD and inform planning for a large randomized trial in this population.

Diagnostic yield of chromosomal microarray analysis in an autism primary care practice: which guidelines to implement?

Genetic testing is recommended for patients with ASD; however specific recommendations vary by specialty. American Academy of Pediatrics and American Academy of Neurology guidelines recommend G-banded karyotype and Fragile X DNA. The American College of Medical Genetics recommends Chromosomal Microarray Analysis (CMA). We determined the yield of CMA (N = 85), karyotype (N = 119), and fragile X (N = 174) testing in a primary pediatrics autism practice. We found twenty (24%) patients with abnormal CMA results (eight were clinically significant), three abnormal karyotypes and one Fragile X syndrome. There was no relationship between CMA result and cognitive level, seizures, dysmorphology, congenital malformations or behavior. We conclude that CMA should be the clinical standard in all specialties for first tier genetic testing in ASD.

Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size.

BACKGROUND: Deletion and the reciprocal duplication in 16p11.2 were recently associated with autism and developmental delay. METHOD: We indentified 27 deletions and 18 duplications of 16p11.2 were identified in 0.6% of all samples submitted for clinical array-CGH (comparative genomic hybridisation) analysis. Detailed molecular and phenotypic characterisations were performed on 17 deletion subjects and ten subjects with the duplication. RESULTS: The most common clinical manifestations in 17 deletion and 10 duplication subjects were speech/language delay and cognitive impairment. Other phenotypes in the deletion patients included motor delay (50%), seizures ( approximately 40%), behavioural problems ( approximately 40%), congenital anomalies ( approximately 30%), and autism ( approximately 20%). The phenotypes among duplication patients included motor delay (6/10), behavioural problems (especially attention deficit hyperactivity disorder (ADHD)) (6/10), congenital anomalies (5/10), and seizures (3/10). Patients with the 16p11.2 deletion had statistically significant macrocephaly (p<0.0017) and 6 of the 10 patients with the duplication had microcephaly. One subject with the deletion was asymptomatic and another with the duplication had a normal cognitive and behavioural phenotype. Genomic analyses revealed additional complexity to the 16p11.2 region with mechanistic implications. The chromosomal rearrangement was de novo in all but 2 of the 10 deletion cases in which parental studies were available. Additionally, 2 de novo cases were apparently mosaic for the deletion in the analysed blood sample. Three de novo and 2 inherited cases were observed in the 5 of 10 duplication patients where data were available. CONCLUSIONS: Recurrent reciprocal 16p11.2 deletion and duplication are characterised by a spectrum of primarily neurocognitive phenotypes that are subject to incomplete penetrance and variable expressivity. The autism and macrocephaly observed with deletion and ADHD and microcephaly seen in duplication patients support a diametric model of autism spectrum and psychotic spectrum behavioural phenotypes in genomic sister disorders.

Parent-based sleep education workshops in autism.

To determine if parents can successfully teach their children with autism spectrum disorders to become better sleepers, we piloted small group parent education workshops focused on behavioral sleep strategies. Workshops consisted of three 2-hour sessions conducted over consecutive weeks by 2 physicians. Curricula included establishing effective daytime and nighttime habits, initiating a bedtime routine, and optimizing parental interactions at bedtime and during night wakings. Baseline and treatment questionnaires and actigraphy were analyzed in 20 children, ages 3 to 10 years. Improvements after treatment were seen in the total scale and several insomnia-related subscales of the Children's Sleep Habits Questionnaire. Actigraphy documented reduced sleep latency in children presenting with sleep onset delay. Improvements were also noted in measures of sleep habits and daytime behavior. Brief parent-based behavioral sleep workshops in children with autism spectrum disorders appear effective in improving subjective and objective measures of sleep, sleep habits, and daytime behavior.

A sleep habits questionnaire for children with autism spectrum disorders.

Sleep difficulties in children with autism spectrum disorders are common, with poor sleep hygiene a contributing factor. We developed the Family Inventory of Sleep Habits to measure sleep hygiene in this population. Its validity and reliability in 2 groups of children aged 4 to 10 years, those with a clinical diagnosis of autism spectrum disorders, and those who are typically developing are described. In both groups, total and modified (reflecting insomnia subscales) scores on the Children's Sleep Habits Questionnaire showed significant negative correlations with the total score. The Peabody Picture Vocabulary Test-III was significantly correlated with total score in the autism spectrum group but not in the typically developing group. Age and socioeconomic status were not correlated with total score in either group. This preliminary work suggests that the Family Inventory of Sleep Habits is a valid and reliable measure of sleep hygiene in autism spectrum disorders.

Melatonin for insomnia in children with autism spectrum disorders.

We describe our experience in using melatonin to treat insomnia, a common sleep concern, in children with autism spectrum disorders. One hundred seven children (2-18 years of age) with a confirmed diagnosis of autism spectrum disorders who received melatonin were identified by reviewing the electronic medical records of a single pediatrician. All parents were counseled on sleep hygiene techniques. Clinical response to melatonin, based on parental report, was categorized as (1) sleep no longer a concern, (2) improved sleep but continued parental concerns, (3) sleep continues to be a major concern, and (4) worsened sleep. The melatonin dose varied from 0.75 to 6 mg. After initiation of melatonin, parents of 27 children (25%) no longer reported sleep concerns at follow-up visits. Parents of 64 children (60%) reported improved sleep, although continued to have concerns regarding sleep. Parents of 14 children (13%) continued to report sleep problems as a major concern, with only 1 child having worse sleep after starting melatonin (1%), and 1 child having undetermined response (1%). Only 3 children had mild side-effects after starting melatonin, which included morning sleepiness and increased enuresis. There was no reported increase in seizures after starting melatonin in children with pre-existing epilepsy and no new-onset seizures. The majority of children were taking psychotropic medications. Melatonin appears to be a safe and well-tolerated treatment for insomnia in children with autism spectrum disorders. Controlled trials to determine efficacy appear warranted.

Impact of treating sleep apnea in a child with autism spectrum disorder.

Sleep disorders can affect daytime functioning in a variety of neurologic conditions, including autism spectrum disorder. This report describes improvements in sleep, social communication, attention, repetitive behaviors, and hypersensitivity after adenotonsillectomy for obstructive sleep apnea in a 5-year-old female with an autism spectrum disorder. Improvements were documented via pre- and postsurgical measures of parent report, polysomnography, validated sleep and behavior scales, and the Autism Diagnostic Observation Schedule. Identification and treatment of sleep disorders, including obstructive sleep apnea, may improve daytime behavior in children with autism spectrum disorders.

Characterizing sleep in children with autism spectrum disorders: a multidimensional approach.

STUDY OBJECTIVES: To relate parentally reported sleep concerns in autism spectrum disorders (ASD) to polysomnographic (PSG) findings and measures of daytime behavior and autism symptomatology. DESIGN: Cross-sectional study involving validated questionnaires, sleep histories and diaries, 2 nights of PSG, and the Autism Diagnostic Observation Schedule (ADOS). SETTING: Vanderbilt University General Clinical Research Center Sleep Core. PARTICIPANTS: 21 children with ASD and 10 typically developing (TD) children, aged 4-10 years. Children were free of psychotropic medications, with no history of mental retardation or epileptic seizures. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Children with ASD were defined as "good sleepers" (10 children) and "poor sleepers" (11 children) on the basis of parental report; the age-comparable TD children were all reported by their parents to be good sleepers. Poor sleepers with ASD showed prolonged sleep latency and decreased sleep efficiency on night 1 of PSG and differed on insomnia-related subscales of the Children's Sleep Habits Questionnaire (CSHQ; increased sleep onset delay and decreased sleep duration). The good sleepers with ASD did not differ from the TD children in sleep architecture or on CSHQ domains. As compared with ASD good sleepers, the ASD poor sleepers also had higher scores related to affective problems on the Child Behavior Checklist and more problems with reciprocal social interaction on the ADOS. CONCLUSIONS: Parentally reported sleep concerns of insomnia in children with ASD are substantiated by validated sleep questionnaires and by PSG. Furthermore, good sleepers with ASD showed fewer affective problems and better social interactions than ASD poor sleepers.