Spot urinary creatinine excretion in pervasive developmental disorders

BACKGROUND: Excretion of creatinine in urine represents the end-point of endogenous energy transfer from stored adenosine triphosphate in skeletal and cardiac muscle. Measurement of urinary creatinine is commonly used to correct for total urine concentration. Various quantitative measures of compounds suspected to be either pathological to, or indicative of, possible therapeutic interventions for Pervasive Developmental Disorders (PDD) have relied extensively on spot creatinine as a ratio quantity, although this important metabolite has not been exclusively studied within this population. METHODS: Levels of urinary creatinine in spot urine samples were analyzed for a group of children diagnosed with PDD (n=24; median age, 75 months; range, 39-137 months) and a control group (n=50; median age, 109 months; range, 59-140 months). Diagnosis of PDD was confirmed using the Autism Diagnostic Interview-Revised. Samples were collected and analyzed blind for creatinine content using an improved Jaffe's reaction method. RESULTS: Controlling for sample pH and body mass index, a significant decrease in urinary creatinine concentration was found in the PDD group compared to controls using a Mann-Whitney two-tailed ranks test (P=0.001). CONCLUSION: Further studies of protein catabolism and renal function in autism are required to ascertain the relevance of decreased spot urinary creatinine excretion identified in this preliminary study. Issues regarding the use of single urine creatinine measurements and associated confounding variables are discussed in light of the findings, together with recommendations to use other internal or external standards for the quantification of urinary compounds in PDD research.     

Annotation: The similarities and differences between autistic disorder and Asperger's disorder: a review of the empirical evidence

Background:  The ongoing controversy over the distinction between autistic disorder and Asperger's disorder is important to resolve because of the implications regarding an understanding of the aetiology and prognosis, and the diagnostic and clinical practices relating to these conditions. This paper provides a critical evaluation of current published research evidence.
Method:  Databases, such as PsychINFO and Medline, as well as book chapters, reference lists from relevant articles, and recent editions of key journals were searched for all relevant studies (until 2002) which incorporated participants diagnosed with high-functioning autism and Asperger's disorder using either cluster analysis or comparative approaches to examine similarities and differences between these groups. Keywords used in the searches included autistic disorder, Asperger's disorder, autism, high-functioning autism, and pervasive developmental disorder.
Results:  On the basis of the available evidence, there seem to be few qualitative differences between autistic disorder and Asperger's disorder.
Conclusion:  There is currently insufficient evidence to establish the validity of Asperger's disorder as a syndrome distinct from high-functioning autism. The findings are consistent with the view that these disorders belong on an autism spectrum.     

Similar developmental trajectories in autism and Asperger syndrome: from early childhood to adolescence

Objective:  The objective of this study was to chart the developmental trajectories of high-functioning children with autism spectrum disorders (ASD) from early childhood to adolescence using the presence and absence of structural language impairment (StrLI) as a way of differentiating autism from Asperger syndrome (AS).
Method:  Sixty-four high-functioning children with ASD were ascertained at 4–6 years of age from several different regional diagnostic and treatment centers. At 6–8 years of age, the ADI-R and the Test of Oral Language Development were used to define an autism group (those with StrLI at 6–8 years of age) and an AS group (those without StrLI). Growth curve analysis was then used to chart the developmental trajectories of these children on measures of autistic symptoms, and adaptive skills in communication, daily living and socialization.
Results:  Differentiating the ASD group in terms of the presence/absence of StrLI provided a better explanation of the variation in growth curves than not differentiating high-functioning ASD children. The two groups had similar developmental trajectories but the group without StrLI (the AS group) was functioning better and had fewer autistic symptoms than the group with StrLI (the autism group) on all measures across time. The differences in outcome could not be explained by non-verbal IQ or change in early language skills.
Conclusion:  Distinguishing between autism and Asperger syndrome based on the presence or absence of StrLI appears to be a clinically useful way of classifying ASD sub-types.     

Comprehension of Affect in Context in Children with Pervasive Developmental Disorders

Fifteen children with Pervasive Developmental Disorders (PDD) (mean age 12.7 years) were compared to mental age matched normal children on matching a context to its appropriate emotion. PDD children were slightly but significantly impaired on this task relative to a non-social task equated for difficulty. Both matching tasks were highly correlated with cognitive variables; the social matching task alone was correlated with social skill level, and neither task was correlated with ratings of social deviance. Results are discussed in terms of the demands of social cognitive tasks, the magnitude of social cognitive findings, control group selection and individual differences.     

Body mass index in male and female children with pervasive developmental disorders

Background: The aim of the present study was to evaluate body mass index (BMI) of children with a pervasive developmental disorder (PDD) attending two university clinics during the 1960–84 period.
Methods: BMI derived from medical records of 83 consecutively admitted children with atypical autism and 115 children with Asperger syndrome were compared with the corresponding BMI percentiles in an age- and sex-matched reference population.
Results: The BMI distribution of the boys, but not the girls, in both diagnostic categories was significantly lower than those of the age-matched reference populations. Approximately 15% of the boys had a BMI below the fifth percentile.
Conclusions: The present findings are comparable to the results of other studies. Particular attention is given to low BMI as a potential endophenotype in boys with PDD.     

Gaze behavior of children with pervasive developmental disorder toward human faces: a fixation time study

BACKGROUND: The abnormal gaze behavior of autistic children toward human faces, as observed in daily-life situations, are investigated in two fixation time studies. It has been argued that faces are a special kind of stimuli for normal individuals and that this might not be the case for autistic children. METHODS: A group of high-functioning autistic children (including a group of sub-threshold PDD-NOS children) was compared with a group of normal children, with respect to their fixation behavior for photographs of human faces. Using an infrared eye-tracking device, fixation times for the whole face and for the facial elements of faces were compared between the two groups. The first study dealt with faces having an emotional expression. The second study dealt with neutral faces presented either upright or upside-down. RESULTS: Results of the two studies showed that autistic children have the same fixation behavior as normal children for upright faces, with or without an emotional expression. Furthermore, results of the second study showed that normal children spent less time looking at upside-down faces, but that the fixation times of autistic children were not influenced by the orientation of the faces. CONCLUSIONS: These results plead against the notion that the abnormal gaze behavior in everyday life is due to the presence of facial stimuli per se. Furthermore, the absence of a face orientation effect in autistic children might be a reflection of a lack of holistic processing of human faces in autism.     

Toxicity biomarkers in autism spectrum disorder: A blinded study of urinary porphyrins

Background: Recent studies suggest that children diagnosed with an autism spectrum disorder (ASD) have significantly increased levels of urinary porphyrins associated with mercury (Hg) toxicity, including pentacarboxyporphyrin (5cxP), precoproporphyrin (prcP), and coproporphyrin (cP), compared to typically developing controls. However, these initial studies were criticized because the controls were not age‐ and gender‐matched to the children diagnosed with an ASD. Methods: Urinary porphyrin biomarkers in a group of children (2–13 years of age) diagnosed with an ASD (n= 20) were compared to matched (age, gender, race, location, and year tested) group of typically developing controls (n= 20). Results: Participants diagnosed with an ASD had significantly increased levels of 5cxP, prcP, and cP in comparison to controls. No significant differences were found in non‐Hg associated urinary porphyrins (uroporphyrins, hexacarboxyporphyrin, and heptacarboxyporphyrin). There was a significantly increased odds ratio for an ASD diagnosis relative to controls among study participants with precoproporphyrin (odds ratio = 15.5, P < 0.01) and coproporphyrin (odds ratio = 15.5, P < 0.01) levels in the second through fourth quartiles in comparison to the first quartile. Conclusion: These results suggest that the levels of Hg‐toxicity‐associated porphyrins are higher in children with an ASD diagnosis than controls. Although the pattern seen (increased 5cxP, prcP, and cP) is characteristic of Hg toxicity, the influence of other factors, such as genetics and other metals cannot be completely ruled out.     

EEG and MRI findings and their relation with intellectual disability in pervasive developmental disorders

Background  The diagnostic category pervasive developmental disorders (PDDs) refer to a group of five disorders: autism, Rett syndrome, childhood disintegrative disorder, Asperger syndrome, and pervasive developmental disorder not otherwise specified (PDD-NOS). EEG abnormalities and seizures are considered much frequent in autistic subjects with comorbid intellectual disability (ID). In this study, we aimed to evaluate the EEG and MRI findings and their relation with ID in pervasive developmental disorder. Methods  A retrospective, cross-sectional and non-experimental study was performed. Subjects included 81 patients diagnosed with autism or PDD-NOS according to the DSM-IV criteria. The age range of the patients was 2–15 years (mean 6.6 years, SD 3.0). Among them, 21 (25.9%) were girls and 60 boys (74.1%). Results  Patients with severe ID had a higher rate of EEG abnormalities (P=0.03) than patients without ID as well as patients with mild or moderate ID. The association remained significant after the structural MRI abnormalities were controlled (P=0.04). The severity of ID was not associated with abnormal MRI. The most frequent EEG and MRI abnormalities were active epileptic anomaly/paroxysmal abnormality and cerebral atrophy/periventricular leukomalacia, respectively. Almost a third of the EEG abnormalities were associated with temporal cortex and adjacent cortical structures. Conclusions  Consistent with previous studies, almost a fourth of the patients in this relatively large sample of patients with pervasive developmental disorders had EEG and/or MRI abnormalities. EEG results indicate that temporal cortex may play a significant role in pervasive developmental disorders.     

Development in infants with autism spectrum disorders: a prospective study

BACKGROUND: Autism is rarely diagnosed before three years of age despite evidence suggesting prenatal abnormalities in neurobiological processes. Little is known about when or how development becomes disrupted in the first two years of life in autism. Such information is needed to facilitate early detection and early intervention. METHODS: This prospective study of autism spectrum disorders (ASD) examined development using the Mullen Scales of Early Learning (MSEL) in 87 infants tested at target ages 6, 14, and 24 months. Participants came from infants at high risk (siblings of children with autism) and low risk (no family history of autism) groups. Based on language test scores, Autism Diagnostic Observation Schedule, and clinical judgment at 24 months of age, participants were categorized as: unaffected, ASD, or language delayed (LD). Longitudinal linear regression and ANOVA models were applied to MSEL raw scores, and estimates were compared between the three diagnostic groups. RESULTS: No statistically significant group differences were detected at 6 months. By 14 months of age, the ASD group performed significantly worse than the unaffected group on all scales except Visual Reception. By 24 months of age, the ASD group performed significantly worse than the unaffected group in all domains, and worse than the language delayed group in Gross Motor, Fine Motor, and Receptive Language. The developmental trajectory of the ASD group was slower than the other groups', and showed a significant decrease in development between the first and second birthdays. CONCLUSIONS: Variations from typical and language delayed development are detectable in many children with ASD using a measure of general development by 24 months of age. Unusual slowing in performance occurred between 14 and 24 months of age in ASD.     

The prevalence of Gilles de la Tourette's syndrome in children and adolescents with autism

Thirty-seven pupils attending a special school for children and adolescents with autism were observed for the presence of motor and vocal tics. Subsequent family interviews confirmed the diagnosis of comorbid Gilles de la Tourette's Syndrome (GTS) in three children with autism, giving a minimum prevalence rate of 8.1 %. Family history data also suggested this was heritable. The presence of GTS was not associated with superior intellectual, language, or social development. Results suggest that the rate of GTS in autism may exceed that expected by chance. The limited sample size constrains this conclusion. A large-scale epidemiological study testing this association study would appear merited.     

Impaired disengagement of attention in young children with autism

BACKGROUND: The present study examined the disengage and shift operations of visual attention in young children with autism. METHODS: For this purpose, we used a simple visual orienting task that is thought to engage attention automatically. Once attention was first engaged on a central fixation stimulus, a second stimulus was presented on either side, either simultaneously or successively. Latency to begin an eye movement to the peripheral stimulus served as the main dependent measure. The two stimulus conditions (simultaneous and successive) provided independent measures of disengaging and shifting attention, respectively. Performance of children with autism was compared to that of children with Down syndrome and a normal group. RESULTS: The main finding was that relative to both comparison groups, children with autism had marked difficulty in disengaging attention. Indeed, on 20% of trials they remained fixated on the first of two competing stimuli for the entire 8-second trial duration. Evidence is also provided for a more subtle problem in executing rapid shifts of attention. CONCLUSIONS: Our findings on disengagement in autism parallel those reported in normal 2-month-olds, in whom attention has been described as 'obligatory'. Discussion focuses on the potential role of general versus domain-specific processes in producing some of the core features of autism.