Six-month sleep-wake organization and stability in preschool-age children with autism, developmental delay, and typical development.

This study examined sleep-wake patterns in 3 matched comparison groups of preschool-aged children: children with autism (AUT), children with developmental delay (DD) without AUT, and children who are developing typically (TYP). Sleep was assessed via actigraphy and parent-report diaries for 7 consecutive 24-hr periods across 3 time points: at enrollment (n = 194), 3 months later (n = 179), and 6 months after enrollment (n = 173). At each recording period, children in the AUT group slept less per 24-hr period, on average, and were less likely to awaken at night than children in the other two groups. In contrast, children in the DD group had more frequent and longer duration nighttime awakenings than children in the AUT group. Overall, children in the 2 neurodevelopmentally disordered groups demonstrated more night-to-night variability in their sleep-wake measures than children in the TYP group.

Sleep problems, sleepiness and daytime behavior in preschool-age children.

BACKGROUND: Sleep problems are a common complaint of parents of preschool children. Children with neurodevelopmental disorders have even more disrupted sleep than typically developing children. Although disrupted nighttime sleep has been reported to affect daytime behavior, the pathway from sleep disruption to sleep problems, to impairments in daytime performance or behavior is not clear. This multi-method, preliminary study assessed this path in 68 children with autism, matched to 57 children with developmental delay without autism and 69 children developing typically. METHODS: Actigraphy, structured questionnaires, laboratory assessments, and parent reports were obtained in 194 children. RESULTS: Controlling for diagnosis and developmental age of the child, nighttime sleep problems determined by parent reports were significantly associated with decrements in daytime behavior, also measured by parent report instruments. However, actigraph-defined sleep problems and objective measures of daytime sleepiness were not associated with decrements in daytime performance. CONCLUSIONS: Parent report measures substantiate relationships between disrupted sleep patterns and waking behavior. Further understanding of the pathway from sleep disorders to daytime sleepiness and decrements in waking performance, however, may require more rigorous methods of assessment such as polysomnography and the multiple sleep latency test.

Objective sleep measurement in typically and atypically developing preschool children with ADHD-like profiles.

OBJECTIVE: This study investigated the association between preschool children's sleep patterns measured by actigraphy and parent-reported hyperactivity symptoms. Many previous studies have reported sleep problems in children with attention deficit hyperactivity disorder (ADHD)-like symptoms. METHODS: This study examined a cross-sectional sample of 186 preschoolers age 2-5 years in three groups: children with autism, children with developmental delay without autism, and typically developing children recruited from the general population. One week of actigraphic sleep data plus a parent report of the presence or absence of a current sleep problem were collected. Parents completed the child behavior checklist; a subset of children in preschool had teachers who completed the caregiver-teacher report form. Sleep behavior was compared for those children with and without clinical levels of attention-deficit/hyperactivity symptoms (T scores > or = 65). RESULTS: The prevalence of a parent-defined sleep problem across the entire sample was 36.1%. Thirty-four percent of the sample had a parent-reported ADHD composite in the clinical range. Those children with a clinical ADHD profile were more likely to be described by parents as having a sleep problem. However, no significant differences in actigraphic sleep patterns or night-to-night sleep-wake variability were found for children with an ADHD profile in the clinical range. CONCLUSIONS: In this non-clinical sample of preschool age children, parental reports of clinical ADHD profiles were significantly associated with parental reports of sleep problems but not with actigraphically recorded sleep-wake data.

The use of actigraphy to study sleep disorders in preschoolers: some concerns about detection of nighttime awakenings.

STUDY OBJECTIVES: This study compared actigraphy with videosomnography in preschool-aged children, with special emphasis on the accuracy of detection of nighttime awakenings. DESIGN: Fifty-eight participants wore an actigraph for 1 week and were videotaped for 2 nights while wearing the actigraph. SETTING: Participants were solitary sleepers, studied in their homes. PARTICIPANTS: One group (n = 22) was diagnosed with autism, another group (n = 11) had developmental delays without autism, and a third group (n = 25) were typically developing children; age ranged from 28 to 73 months (mean age 47 months); 29 boys and 29 girls. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Nocturnal sleep and wakefulness were scored from simultaneously recorded videosomnography and actigraphy. The accuracy of actigraphy was examined in an epoch-by-epoch comparison with videosomnography. Findings were 94% overall agreement, 97% sensitivity, and 24% specificity. Statistical corrections for overall agreement and specificity resulted in an 89% weighted-agreement and 27% adjusted specificity. CONCLUSIONS: Actigraphy has poor agreement for detecting nocturnal awakenings, compared with video observations, in preschool-aged children.

Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: a population-based study.

This study compared parent-reported sleep characteristics in 2- to 5-year-old children with autism spectrum disorders (ASD) to children with other developmental delays (DD) and typical development (TD). We included 529 children (303 ASD [167 males], 63 DD [46 males], and 163 TD [134 males]) enrolled in the CHARGE study, an ongoing population-based case-control study. The mean age of participants was 3.6 years (standard deviation, 0.8 years). ASD diagnosis was confirmed with Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedules (ADOS). Cognitive and adaptive functioning was assessed using Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS), respectively. Demographic, medical and sleep history information were ascertained from California birth records, telephone interview, medical assessments at clinic visit, and parent-administered questionnaires. Fifty-three percent of children with ASD had at least one frequent sleep problem, followed by 46% of children with DD, and 32% of the TD group (P < 0.0001). Exploratory factor analyses of sleep history data yielded two factors: sleep onset problems and night waking. Children with ASD had marginally higher sleep onset factor scores and significantly higher night waking factor scores compared with the TD group. Factor scores for children with DD were intermediate between the ASD and TD groups. Cognitive or adaptive development did not predict severity of sleep problems in the ASD group.

The effectiveness of parent-child interaction therapy for families of children on the autism spectrum.

We report the results of a pilot trial of an evidence-based treatment-Parent-Child Interaction Therapy (PCIT; Eyberg et al. Psychopharmacology Bulletin, 31(1), 83-91, 1995) for boys aged 5-12 with high functioning autism spectrum disorders and clinically significant behavioral problems. The study also included an investigation of the role of shared positive affect during the course of therapy on child and parent outcomes. The intervention group showed reductions in parent perceptions of child problem behaviors and child atypicality, as well as an increase in child adaptability. Shared positive affect in parent child dyads and parent positive affect increased between the initial and final phases of the therapy. Parent positive affect after the first phase was related to perceptions of improvement in problem behaviors and adaptive functioning.

The Children's Sleep Habits Questionnaire in toddlers and preschool children.

OBJECTIVE: Twenty to 40% of young children are reported to have behavioral insomnias of childhood. Concerns about sleep at these ages are the most common problem expressed to pediatricians at the time of well child visits. A screening questionnaire, the Children's Sleep Habits Questionnaire (CSHQ), has been used in clinical settings and in research studies to assess children ages 4 to 10 for the presence of sleep problems. A CSHQ total score has distinguished clinical populations from community samples. METHODS: The current study assesses the CSHQ in a younger age group than previously reported and in a diverse population. A total of 194 children, ages 2 to 51/2 years, were recruited into 3 diagnostic groups: 68 children with autism, 57 children with developmental delay without autism, and 69 typically developing children. All children's parents completed the CSHQ and a sleep log, and all children were studied for 7 days and nights with actigraphy. The children were divided into problem sleep and non-problem sleep groups on the basis of a parent report of a generic sleep problem at the time of entry into the study. The CSHQ responses for the problem and non-problem sleep groups were then compared. RESULTS: The results suggest that the CSHQ is clinically useful for screening of sleep problems in typically developing children at these young ages as well as in children with diverse neurodevelopmental diagnoses. CONCLUSIONS: The somewhat higher subscale scores than previously reported for older children appear to be consistent with more sleep problems in younger children.

Autism profiles of males with fragile X syndrome.

Autism, which is common in individuals with fragile X syndrome, is often difficult to diagnose. We compared the diagnostic classifications of two measures for autism diagnosis, the ADOS and the ADI-R, in addition to the DSM-IV-TR in 63 males with this syndrome. Overall, 30% of the subjects met criteria for autistic disorder and 30% met criteria for PDD-NOS. The classifications on the ADOS and DSM-IV-TR were most similar, whereas the ADI-R classified subjects as autistic much more frequently. We further investigated the relationship of both FMRP and FMRI mRNA to symptoms of autism in this cohort and found no significant relationship between the measures of autism and molecular features, including FMRP, FMRI mRNA, and CGG repeat number.

The Prader-Willi phenotype of fragile X syndrome.

The Prader-Willi phenotype (PWP) of fragile X syndrome (FXS) is associated with obesity and hyperphagia similar to Prader-Willi syndrome (PWS), but without cytogenetic or methylation abnormalities at 15q11-13. Thirteen cases of PWP and FXS are reported here that were identified by obesity and hyperphagia. Delayed puberty was seen in 5 of 9 cases who had entered puberty, a small penis or testicles in seven of 13 cases, and infant hypotonia and/or a poor suck in seven of 13 cases. Autism spectrum disorder occurred in 10 of 13 cases, and autism was diagnosed in seven of 13 cases. We investigated cytoplasmic interacting FMR1 protein (CYFIP) expression, which is a protein that interacts with FMR1 protein (FMRP) because the gene for CYFIP is located at 15q11-13. CYFIP mRNA levels were significantly reduced in our patients with the PWP and FXS compared to individuals without FXS (p < .001) and also individuals with FXS without PWP (p = .03).

Modified Children's sleep habits questionnaire for behavioral sleep problems: A validation study.

OBJECTIVES: Behavioral sleep problems (BSPs) are prevalent and consequential in young children. There is a need for screening tools that identify BSPs-which are often rooted in the parent-young child relationship-and typically respond to behavior management. Such a tool would increase capacity to identify and treat BSPs. We sought to validate a short-form version of the widely used Children's Sleep Habits Questionnaire (SF-CSHQ) that omitted items that would not be responsive to behavioral strategies. METHODS: The original 33-item CSHQ elicits parent report of "behaviorally-based" and "medically-based" sleep items (eg, parasomnias and sleep disordered breathing). We conducted analyses to develop a SF-CSHQ that excludes its "medically-based" items, to determine (a) the SF-CSHQ threshold score corresponding to the full CSHQ clinical cut-off score (≥41), and (b) preliminary validity of this SF-CSHQ. Data were re-analyzed from the original data that established the CSHQ's psychometric properties in 4-10 year olds, and a second dataset that established its validity in 24-66 month olds. RESULTS: In both datasets, a threshold score of 30 had correlations of 0.90-0.94 with the original cut-off. This 23-item SF-CSHQ cut-off functioned as well as the full CSHQ cut-off in discriminating between children with vs without a parent-reported behavioral sleep problem, and with vs without prolonged sleep latency (per actigraphy). CONCLUSION: We established preliminary validity of modified version of the widely-used CSHQ. This SF-CSHQ may be useful for widening screening and first-line guidance for behavioral sleep problems in young children, among professionals who are not sleep medicine specialists.

Psychiatric phenotype of the fragile X-associated tremor/ataxia syndrome (FXTAS) in males: newly described fronto-subcortical dementia.

OBJECTIVE: The authors describe and quantify the neuropsychiatric symptoms present in a cohort of males with the fragile X mental retardation 1 (FMR1) premutation allele who have developed fragile X-associated tremor/ataxia syndrome (FXTAS). METHOD: Fourteen male carriers of the FMR1 premutation who had clinical manifestations of the FXTAS syndrome and 14 age- and education-matched controls were assessed with the Neuropsychiatric Inventory (NPI), formal cognitive testing, and genetic analysis. RESULTS: Males with FXTAS had significantly higher total NPI scores (p < .004) and significantly higher scores on the agitation/aggression (p < .004), depression (p < .004), apathy (p < .004), disinhibition (p < .004), and irritability (p < .004) scales, compared with controls. Cognitive performances on the Mini-Mental State Examination did not correlate with severity of symptoms on the NPI. CONCLUSIONS: The neuropsychiatric manifestations of FXTAS, based on this preliminary report, appear to cluster as a fronto-subcortical dementia. Clinicians encountering patients with clinical dementia with motor symptoms suggesting FXTAS should consider genetic testing to determine whether the patient's dementia syndrome is secondary to a fragile X premutation carrier status.

Sleep Architecture in Infants of Substance-Abusing Mothers.

This longitudinal, year-long study compared sleep-wake state organization in two groups of infants-infants whose mothers abused substances during their pregnancies and nonexposed, typically developing, age-matched comparison infants-to determine whether differences in sleep-wake state organization existed between the two groups. Seventeen infants of mothers who were participating in a parent-infant residential treatment program for substance abuse were enrolled. Their sleep-wake state organization over the first year of life was compared to that of 17 age-matched comparison infants. The intent was to follow each infant on five occasions over the first year of life using established methods of time-lapse videosomnography to record sleep-wake state organization; however, attrition in the substance-abusing group was problematic. Some sleep-wake variables (i.e., Active Sleep%, Quiet Sleep%, Awake%, number of nighttime awakenings) were similar for both groups of infants at comparable ages across the first year. Total sleep time and the longest sustained sleep period (sleep continuity variables) differed significantly at some of the ages measured. Although overall sleep architecture appears highly resilient and well organized, some indications of sleep fragmentation and shortened nighttime sleep periods were observed in the substance-exposed infants. More research is needed to explain why sleep-continuity variables and not sleep-state proportion variables differed between the two groups.

Methods for acquiring MRI data in children with autism spectrum disorder and intellectual impairment without the use of sedation.

BACKGROUND: Magnetic resonance imaging (MRI) has been widely used in studies evaluating the neuropathology of autism spectrum disorder (ASD). Studies are often limited, however, to higher functioning individuals with ASD. MRI studies of individuals with ASD and comorbid intellectual disability (ID) are lacking, due in part to the challenges of acquiring images without the use of sedation. METHODS: Utilizing principles of applied behavior analysis (ABA), we developed a protocol for acquiring structural MRI scans in school-aged children with ASD and intellectual impairment. Board certified behavior analysts worked closely with each child and their parent(s), utilizing behavior change techniques such as pairing, shaping, desensitization, and positive reinforcement, through a series of mock scanner visits to prepare the child for the MRI scan. An objective, quantitative assessment of motion artifact in T1- and diffusion-weighted scans was implemented to ensure that high-quality images were acquired. RESULTS: The sample consisted of 17 children with ASD who are participants in the UC Davis Autism Phenome Project, a longitudinal MRI study aimed at evaluating brain developmental trajectories from early to middle childhood. At the time of their initial scan (2-3.5 years), all 17 children had a diagnosis of ASD and development quotient (DQ) <70. At the time of the current scan (9-13 years), 13 participants continued to have IQs in the range of ID (mean IQ = 54.1, sd = 12.1), and four participants had IQs in the normal range (mean = 102.2, sd = 7.5). The success rate in acquiring T1-weighted images that met quality assurance for acceptable motion artifact was 100 %. The success rate for acquiring high-quality diffusion-weighted images was 94 %. CONCLUSIONS: By using principles of ABA in a research MRI setting, it is feasible to acquire high-quality images in school-aged children with ASD and intellectual impairment without the use of sedation. This is especially critical to ensure that ongoing longitudinal studies of brain development can extend from infancy and early childhood into middle childhood in children with ASD at all levels of functioning, including those with comorbid ID.

The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages.

Autism is a neurodevelopmental disorder characterized by impairments in reciprocal social interaction, deficits in verbal and nonverbal communication, and a restricted repertoire of activities or interests. We performed a magnetic resonance imaging study to better define the neuropathology of autistic spectrum disorders. Here we report findings on the amygdala and the hippocampal formation. Borders of the amygdala, hippocampus, and cerebrum were defined, and their volumes were measured in male children (7.5-18.5 years of age) in four diagnostic groups: autism with mental retardation, autism without mental retardation, Asperger syndrome, and age-matched typically developing controls. Although there were no differences between groups in terms of total cerebral volume, children with autism (7.5-12.5 years of age) had larger right and left amygdala volumes than control children. There were no differences in amygdala volume between the adolescent groups (12.75-18.5 years of age). Interestingly, the amygdala in typically developing children increases substantially in volume from 7.5 to 18.5 years of age. Thus, the amygdala in children with autism is initially larger, but does not undergo the age-related increase observed in typically developing children. Children with autism, with and without mental retardation, also had a larger right hippocampal volume than typically developing controls, even after controlling for total cerebral volume. Children with autism but without mental retardation also had a larger left hippocampal volume relative to controls. These cross-sectional findings indicate an abnormal program of early amygdala development in autism and an abnormal pattern of hippocampal development that persists through adolescence. The cause of amygdala and hippocampal abnormalities in autism is currently unknown.

Investigation of neuroanatomical differences between autism and Asperger syndrome.

BACKGROUND: Autism and Asperger syndrome (ASP) are neurobiological conditions with overlapping behavioral symptoms and of unknown etiologies. Results from previous autism neuroimaging studies have been difficult to replicate, possibly owing to site differences in subject samples, scanning procedures, and image-processing methods. We sought (1) to determine whether low-functioning autism (LFA; IQ<70), high-functioning autism (HFA; IQ>or=70), and ASP constitute distinct biological entities as evidenced by neuroanatomical measures, and (2) to assess for intersite differences. METHODS: Case-control study examining coronally oriented 124-section spoiled gradient echo images acquired on 3 magnetic resonance imaging (MRI) systems, and processed by BrainImage 5.X. Participants were recruited and underwent scanning at 2 academic medicine departments. Participants included 4 age-matched groups of volunteer boys aged 7.8 to 17.9 years (13 patients with LFA, 18 with HFA, 21 with ASP, and 21 control subjects), and 3 volunteer adults for neuroimaging reliability. Main outcome measures included volumetric measures of total, white, and gray matter for cerebral and cerebellar tissues. RESULTS: Intersite differences were seen for subject age, IQ, and cerebellum measures. Cerebral gray matter volume was enlarged in both HFA and LFA compared with controls (P =.009 and P =.04, respectively). Cerebral gray matter volume in ASP was intermediate between that of HFA and controls, but nonsignificant. Exploratory analyses revealed a negative correlation between cerebral gray matter volume and performance IQ within HFA but not ASP. A positive correlation between cerebral white matter volume and performance IQ was observed within ASP but not HFA. CONCLUSIONS: Lack of replication between previous autism MRI studies could be due to intersite differences in MRI systems and subjects' age and IQ. Cerebral gray tissue findings suggest that ASP is on the mild end of the autism spectrum. However, exploratory assessments of brain-IQ relationships reveal differences between HFA and ASP, indicating that these conditions may be neurodevelopmentally different when patterns of multiple measures are examined. Further investigations of brain-behavior relationships are indicated to confirm these findings.

A social adjustment enhancement intervention for high functioning autism, Asperger's syndrome, and pervasive developmental disorder NOS.

This paper reports the findings of a 20-week social adjustment enhancement curriculum for boys aged 8-12. The curriculum was designed to address three areas hypothesized to be deficient in persons with HFA, AS, and PDDNOS: emotion recognition and understanding; theory of mind; and executive functions/real life type problem solving. Parents attended a semi-structured concurrent psychoeducational training meeting during children's sessions. Statistically significant improvements in facial expression recognition, and problem solving were reported for intervention group children compared to waiting list control group children. For the intervention group (the only group for whom data were available), older and less cognitively able boy's scores on a depression inventory decreased significantly more than younger children's. Mother's depression scores tended to decrease and there were significant reductions in child problem behaviors reported. Results are discussed in the context of individual differences in participant cognitive levels and profiles, symptom severity, and affect-related variables.

Sleep patterns of children with pervasive developmental disorders.

Data on sleep behavior were gathered on 100 children with pervasive developmental disorders (PDD), ages 2-11 years, using sleep diaries, the Children's Sleep Habits Questionnaire (CSHQ), and the Parenting Events Questionnaire. Two time periods were sampled to assess short-term stability of sleep-wake patterns. Before data collection, slightly more than half of the parents, when queried, reported a sleep problem in their child. Subsequent diary and CSHQ reports confirmed more fragmented sleep in those children who were described by their parents as having a sleep problem compared to those without a designated problem. Interestingly, regardless of parental perception of problematic sleep, all children with PDD exhibited longer sleep onset times and greater fragmentation of sleep than that reported for age-matched community norms. The results demonstrate that sleep problems identified by the parent, as well as fragmentation of sleep patterns obtained from sleep diary and CSHQ data, exist in a significant proportion of children with PDD.

Autistic spectrum disorder and the fragile X premutation.

Fragile X syndrome (FXS) is the most common inherited cause of mental retardation. It is also one of the most common identifiable causes of Autism Spectrum Disorder (ASD). Carriers of FXS are often considered to be cognitively and behaviorally unaffected. However, we report here on six individuals in the premutation range who also have ASD. A comparison is made with five subjects in the premutation range who did not receive a diagnosis of ASD. The six individuals with ASD had a range of cognitive ability levels from no impairment to moderate retardation. Discussion includes the impact of molecular variables including lowered FMR1 protein and elevated FMR1 mRNA in addition to environmental factors leading to the complex neurodevelopmental disorder of ASD.

Benefits of an insulin dosage calculation device for adolescents with type 1 diabetes mellitus.

OBJECTIVE: Multiple daily injection insulin regimens (MDI) and continuous subcutaneous insulin infusion (CSII) allow adolescents with type 1 diabetes mellitus (DM) meal flexibility, and may improve metabolic control. The insulin dosage calculations, however, involve ratios of insulin to carbohydrate and corrections for high blood glucose values, and are labor-intensive and prone to error. We evaluated the impact of an insulin dosage calculation device (IDC) on metabolic control, treatment satisfaction, regimen adherence and quality of life in adolescents using MDI or CSII. RESEARCH DESIGN AND METHODS: We conducted a randomized control trial using the IDC in 83 adolescents on MDI or CSII. At enrollment, patients received training on dosage calculation using either the IDC or conventional methods, and performed sample calculations. At enrollment, 6 months and 12 months, we recorded HbA1c and frequency of hypoglycemia, and patients completed questionnaires assessing treatment satisfaction, regimen adherence and quality of life. After 6 months, patients in the control group were also given the IDC. RESULTS: We observed a higher frequency of errors with conventional calculations (53-67% incorrect calculations) than with the IDC (25-32% incorrect). At 6 months, there was a trend toward improved HbA1c in the IDC group overall (9.3 vs 8.9, p = 0.07) and a significant improvement in the subset (42%) who used the IDC consistently (9.7 vs 8.8, p = 0.03). There was no change in HbA1c in the control group during this interval (9.0 vs 8.9, p = 0.90). During months 6-12, when both groups were combined, there was a significant increase in HbA1c in patients using the IDC inconsistently or not at all (8.9 vs 9.4, p = 0.005), but no change in HbA1c in those using the IDC consistently (9.1 vs 8.9, p = 0.57). Treatment satisfaction, adherence and quality of life improved throughout the study in both groups. CONCLUSIONS: Errors in calculation of insulin dosage by adolescents occur frequently. Consistent use of an insulin dosage calculation device may help to improve metabolic control in adolescents using MDI or CSII.

Social impairments in chromosome 22q11.2 deletion syndrome (22q11.2DS): autism spectrum disorder or a different endophenotype?

High prevalence of autism spectrum disorders (ASD) has been reported in 22q11.2DS, although this has been based solely on parent report measures. This study describes the presence of ASD using a procedure more similar to that used in clinical practice by incorporating history (Social Communication Questionnaire) AND a standardized observation measure (Autism Diagnostic Observation Schedule) and suggests that ASD is not as common as previously reported in 22q11.2DS. Differences in methodology, along with comorbid conditions such as anxiety, likely contribute to false elevations in ASD prevalence and information from multiple sources should be included in the evaluation of ASD.