Current status of differential diagnosis for children with autism spectrum disorders

Early intervention for autism spectrum disorder (ASD) has proven to be a successful strategy for remediating many difficulties experienced by these children. As a result, accurate diagnoses of children with this range of disorders has become more critical. Additionally, while current training programs are for 3-4 year olds, in efforts to start treatment at younger ages, clinicians are giving these diagnoses at younger and younger ages. A considerable amount of research activity on a technology for making differential diagnoses of ASD has been emerging in recent years. The purpose of this paper is to provide an overview of some of these developments, and to offer opinions on the current status of the area.     

Sleep in children with autism spectrum disorders

The amount of research conducted on sleep in children and adolescents has increased dramatically over the past decade due to the recognition that many children have significant sleep problems leading to daytime dysfunction. Approximately one third of typically developing children have sleep difficulties at some point, and a similar percentage of adolescents have impaired or insufficient sleep leading to daytime impairments. Sleep problems are known to occur at even greater rates in children with special needs, such as those with developmental disabilities, psychiatric conditions, and medical illnesses. The recognition that interventions can improve sleep and may result in better daytime functioning has fueled a growing interest in more fully characterizing the sleep problems in children with special needs. This article presents a discussion of the sleep problems experienced by children with one particular group of developmental disorders—the autism spectrum disorders.     

Macrocephaly in children with autism spectrum disorders

Research indicates the presence of macrocephaly or abnormally large head circumferences in children with autism and spectrum-related disorders, compared with their typically developing peers. Previous research, however, centered on non-nationally representative, clinic-based samples of children and adults with autism spectrum disorders. Moreover, these samples were typically small. The present study represents results of a nationally representative, community-based sample of children with and without autism spectrum disorders, derived from the Early Childhood Longitudinal Study Birth Cohort. Results reveal statistically nonsignificant differences in the head circumferences of children with autism spectrum disorders across three time points, compared with children without autism spectrum disorders. These results may be considered highly generalizable, because they are derived from a nationally representative, community-based sample of children with and without autism spectrum disorders from the Early Childhood Longitudinal Study Birth Cohort.     

Electroencephalographic studies in children with autism spectrum disorders

An important factor in the diagnosis and treatment of Autism spectrum disorder (ASD) is prescribed Electroencephalography (EEG). EEG changes may show the following: slowing, asymmetry, sharp waves or spikes, sharp and slow waves, generalized sharp and slow waves, or generalized polyspikes in a distributed or general area, multifocal or focal, unilateral or bilateral, and they may be located in many different areas of the brain. There is a need to look for a EEG phenotype typical of patients with ASD. The importance of gamma waves, rhythm mu, mirror neurons, and their role in patients with ASD was discussed. Epilepsy is reported to occur in one third of ASD patients. In ASD, seizures and EEG paroxysmal abnormalities could represent an epiphenomenon of a cerebral dysfunction independent of apparent lesions. This article reviews ASD and EEG abnormalities and discusses the interaction between epileptiform abnormalities and cognitive dysfunction.     

Understanding macrographia in children with autism spectrum disorders

It has been consistently reported that children with autism spectrum disorders (ASD) show considerable handwriting difficulties, specifically relating to accurate and consistent letter formation, and maintaining appropriate letter size. The aim of this study was to investigate the underlying factors that contribute to these difficulties, specifically relating to motor control. We examined the integrity of fundamental handwriting movements and contributions of neuromotor noise in 26 children with ASD aged 8–13 years (IQ > 75), and 17 typically developing controls. Children wrote a series of four cursive letter l's using a graphics tablet and stylus. Children with ASD had significantly larger stroke height and width, more variable movement trajectory, and higher movement velocities. The absolute level of neuromotor noise in the velocity profiles, as measured by power spectral density analysis, was significantly higher in children with ASD; relatively higher neuromotor noise was found in bands >3 Hz. Our findings suggest that significant instability of fundamental handwriting movements, in combination with atypical biomechanical strategies, contribute to larger and less consistent handwriting in children with ASD.     

Use of clonidine in children with autism spectrum disorders

Children with autism spectrum disorders (ASD) often exhibit sleep and behavioral disorders. Treatment of sleep disorders can be difficult in these children. Clonidine, an alpha2-adrenergic receptor agonist, has been shown to be effective in reducing impulsivity, inattention, and hyperactivity, as well as in serving as a sedative for medial procedures. An open labeled retrospective study of clonidine in treatment of insomnia, and/or hyperactivity, inattention, mood disorder, and aggressive behaviors was conducted using parent reports of sleep initiation and maintenance, as well as behaviors prior and during clonidine treatment. Clonidine was effective in reducing sleep initiation latency and night awakening, to a less degree in improving attention deficits hyperactivity, mood instability and aggressiveness in this cohort of 19 children with ASD. The side effects were largely tolerable. Further evaluation with placebo-controlled double-blind clinical trial of clonidine use in ASD will provide more insight into the clinical efficacy and safety of the medicine in ASD.     

Medication use among children with autism spectrum disorders

The study characterizes the use of psychoactive medications among children and youth with autism-spectrum disorders over the course of a calendar year. Eighty-three percent of the sample had at least one drug claim during the year. Prescribed drugs came from 125 different therapeutic classes. The seven most frequently prescribed classes of psychoactive drugs were antidepressants, stimulants, tranquilizers/antipsychotics, anticonvulsants, hypotensive agents, anxiolytic/sedative/hypnotics, and benzodiazepines. The data on other relevant diagnoses indicate that children and youth are frequently treated with medication under an autism-spectrum diagnosis, even though the target symptoms may be commonly associated with other mental disorders. Age data indicate that about 70% of children with autism-spectrum disorders age 8 yr and up receive some form of psychoactive medication in a given year.     

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.     

Mood symptoms in children and adolescents with autism spectrum disorders

Asperger Syndrome (AS) and High Functioning Autism (HFA) are psychiatric conditions belonging to the Autistic Spectrum Disorders (ASDs), characterized by social dysfunction and focused interest, in the absence of mental retardation. Previous reports suggest that AS/HFA may be associated with important psychiatric comorbidities. Among the psychiatric internalizing disorders, depression and anxiety are probably the most common disorders. The aim of this study is to evaluate the prevalence of mood disorders and identifying peculiar clinical features in subjects suffering from AS and HFA. 30 male patients with AS/HFA, 30 male patients affected by Major Depression (MD) and 35 male Typically Developing (TD) comparison were assessed with the CDI and the CDRS-R. Participants’ parents were invited to complete the CBCL and the P-YMRS. Moreover, the CGAS was rated by the clinicians. The evaluation of depressive symptoms showed that AS/HFA group reported higher depressive symptoms, as showed by CDI total, CBCL internalizing and CDRS-R total, compared to the TD group. No significant difference of depressive symptoms was found between the AS/HFA and the MD group, with the exception of CDRS-R total score. Moreover, linear regression analysis in the AS/HFA group between CGAS and depressive symptoms revealed that a higher level of depressive symptoms increased the risk of poorer global functioning. These results suggest that the depressive symptoms in AS/HFA patients may be associated with poorer global functioning, with a consequent impairment in their psychological profile and social adjustment, and should alert clinicians to the importance of assessing mood disorders in order to choose the appropriate treatment.     

A review of methodological issues in the differential diagnosis of autism spectrum disorders in children

The development of standardized tests to assess autism, particularly in young children, is a topic of considerable interest in the research community. Recent years have seen an exponential growth in scales for differential diagnosis. Particular emphasis has been placed on defining and better delineating the symptoms of the disorder relative to other forms of autism spectrum disorder (ASD) and intellectual disability (ID), and identifying the condition at the earliest possible age. The general consensus is that scaling methods are the core means of establishing a diagnosis. Thus, analyzing the research activity in the area for strengths and weaknesses in methodology would appear to be in order. A critical overview of existing psychometric properties of these tests is presented with suggestions for future research on the topic.     

Physical aggression in children and adolescents with autism spectrum disorders

Aggression is a clinically significant problem for many children and adolescents with autism spectrum disorders (ASD). However, there have been few large-scale studies addressing this issue. The current study examined the prevalence and correlates of physical aggression in a sample of 1584 children and adolescents with ASD enrolled in the Autism Treatment Network. The prevalence of aggression was 53%, with highest prevalence among young children. Aggression was significantly associated with a number of clinical features, including self-injury, sleep problems, sensory problems, GI problems, communication and social functioning. In multivariate models, self-injury, sleep problems, and sensory problems were most strongly associated with aggression. The results indicate that aggression is markedly prevalent, and clinical implications and directions for future research are discussed.     

Investigating the validity of a structured interview protocol for assessing the preferences of children with autism spectrum disorders

Purpose: To investigate the congruent validity of a structured interview protocol for assessing the preferences of seven children with autism spectrum disorder (ASD).

Method: Using the structured interview protocol described by Green et al., parents were asked to provide a rank ordering of their child's preferred foods, drinks, toys and sensory stimuli. The resulting rank order was then compared to the results of a multiple-stimulus without replacement preference assessment by calculating the Spearman rank order correlation coefficients.

Results: The results revealed a high level of correspondence between the rank orderings of both assessments for four of the six participants for food and drink items and four of the seven participants for play items and sensory stimuli.

Conclusion: Results support the use of the structured interview protocol to determine the preferences of children with ASD. Practical implications and directions for future research are discussed.     

Assessment of anxiety in children and adolescents with autism spectrum disorders

Anxiety disorders are among the most common comorbid conditions in children and adolescents with autism spectrum disorders (ASDs), although assessment presents unique challenges. Many symptoms of anxiety appear to overlap with common presentations of autism. Furthermore, deficits in language and cognitive functioning make it difficult for such children to convey their emotional states accurately. A comprehensive review of the recent literature was conducted to assay the types and rates of use of tools for evaluating anxiety symptoms in children and adolescents with ASDs. We identified strengths and weaknesses in existing scales, identified instruments that (although imperfect) seem to have a good coverage for youngsters with ASDs, recommended strategies for studying anxiety in these youth, and offered suggestions for future scale development.     

Gangliosides in cerebrospinal fluid in children with autism spectrum disorders

Gangliosides are sialic acid-containing glycolipids found in all cells, especially abundant in nerve cells and mainly situated on outer-membrane surfaces. The aim of this study was to provide data on the concentration of gangliosides in the CSF of children and adolescents with autism spectrum disorders (ASD) - 66 with autistic disorder, and 19 with other autism spectrum disorders. The comparison group consisted of 29 children and adolescents, whose CSF had been sampled to exclude acute infectious CNS disorder. The concentrations of the gangliosides GM1, GD1a, GD1b, and GT1b were determined using a microimmunoaffinity technique. The ASD group had a significantly higher concentration of ganglioside GM1 compared with the comparison group. The GM1 increase could not be explained as secondary to other clinical factors. Mean ganglioside levels did not differentiate subgroups with autistic disorder and those with a more atypical clinical picture, nor subgroups with known medical disorders and those with idiopathic autism. Altered patterns of gangliosides in the CNS might reflect important correlates of pathogenesis in autism.     

Early language milestones predict later language,but not autism symptoms in higher functioning children with autism spectrum disorders

Language ability is a known predictor of outcome in children with autism but plays a more controversial role for higher functioning children with autism spectrum disorders (ASD). We studied the relationship between early language milestones and later structural language, adaptive functioning and autism symptoms in a sample of 76 children (mean age = 9.1 years) with an ASD, using two different language milestones: first phrase by 24 or 36 months. After controlling for age and nonverbal abilities, retrospectively reported early language milestones were predictive of later structural language abilities, measured by a sentence repetition task, and adaptive communication skills, but not autism symptoms or adaptive social skills. Acquisition of phrase speech by 24 months was sensitive to language and communication impairments in our ASD group, the majority (84%) of which had already acquired phrase speech by 36 months of age. Early available and easily collectable milestone data may be a useful marker of later language performance even in higher functioning, verbal children on the autism spectrum. When a detailed assessment of language is not possible, data on early milestones may be useful for identifying children at-risk in clinical settings and for language phenotyping in the laboratory.     

Desire for social interaction in children with autism spectrum disorders

In this experimental clinical study, a first attempt was made to examine the desire for social interaction in children with autism spectrum disorders (ASD). Children with ASD and typically developing (TD) children completed both an explicit measure (self-report) and an implicit measure (Face Turn Approach–Avoidance Task) of the desire for social interaction. On the explicit assessment, children with ASD clearly displayed lower scores reflecting less desire for social interaction than TD children. On the implicit assessment, children with ASD showed a stronger tendency to pull both social and non-social stimuli towards them, which indicates a general automatic tendency towards approach, as compared to the TD children. Possible reasons for this dissociation between the explicit and implicit desire for social interaction are discussed and directions for future research are provided.     

Neurofeedback improves executive functioning in children with autism spectrum disorders

Seven autistic children diagnosed with autism spectrum disorders (ASD) received a neurofeedback treatment that aimed to improve their level of executive control. Neurofeedback successfully reduced children's heightened theta/beta ratio by inhibiting theta activation and enhancing beta activation over sessions. Following treatment, children's executive capacities were found to have improved greatly relative to pre-treatment assessment on a range of executive function tasks. Additional improvements were found in children's social, communicative and typical behavior, relative to a waiting list control group. These findings suggest a basic executive function impairment in ASD that can be alleviated through specific neurofeedback treatment. Possible neural mechanisms that may underlie neurofeedback mediated improvement in executive functioning in autistic children are discussed.     

Teaching children with autism spectrum disorders to cooperate with injections

When injections are necessary, young people with autism spectrum disorders (ASD) may exhibit responses that compromise their health care. Parents often report that their children with ASD struggle or attempt to flee when immunizations or other injections are attempted. This report describes our evaluation of procedures that enable children to cooperate with injections. A changing-criterion design with two replications in the United States and three replications in Turkey was used to assess the performance of five boys and one girl with ASD, ages 8–16. The teaching procedures, conducted in school settings, were relatively errorless. During generalization programming, the participants’ skills transferred to different instructors who played the role of medical practitioner and to different school and community settings. Subsequently, in medical settings, they cooperated with doctors and nurses and successfully received important injections, such as long-overdue diphtheria, tetanus, and pertussis (DTaP) immunizations, tetanus boosters, and influenza and hepatitis B immunizations.     

Flexibility in children with autism spectrum disorders (ASD): inconsistency between neuropsychological tests and parent-based rating scales

In this study, we compared neuropsychological tests and parent-based ratings of flexibility in a sample of children with autism spectrum disorders (ASD). We investigated the discriminant validity of the domain-specific flexibility measures by comparison with the domain general measures, general behavioral problems, general ASD-related traits, and general intelligence. Tests and parent-based ratings of flexibility were not significantly correlated. Parent-based ratings were strongly related with the three broadband measures, whereas the discriminant validity indices of the neuropsychological tests were satisfactory. These findings suggest that parent-based ratings do not reflect the specific executive construct of flexibility, but instead reflect a broad spectrum of general child characteristics.