Monoamine Oxidase Activity in Blood-Platelets From Autistic Children

In order to evaluate the possible abnormality in monoamine oxidase (MAO) activity in early infantile autism, blood platelet samples were obtained from 20 autistic children, aged 2–12 years. MAO activity, measured fluorometrically using serotonin as substrate, was 5.24 ± 1.65 (Mean ± Standard Deviation) nM/mg protein/hour in these autistic children. This value was not significantly different from either that in 30 age-matched normal children or that in 39 nonautistic children with various psychiatric and neurological disorders, although autistic children had higher platelet serotonin concentrations than these nonautistic individuals.     

Monoamine oxidase activity in blood platelets from autistic children

In order to evaluate the possible abnormality in monoamine oxidase (MAO) activity in early infantile autism, blood platelet samples were obtained from 20 autistic children, aged 2--12 years. MAO activity, measured fluorometrically using serotonin as substrate, was 5.24 +/- 1.65 (Mean +/- Standard Deviation) nM/MG protein/hour in these autistic children. This value was not significantly different from either that in 30 age-matched normal children or that in 39 nonautistic children with various psychiatric and neurological disorders, although autistic children had higher platelet serotonin concentration than these nonautistic individuals.     

DSM-III and DSM-III-R diagnoses of autism

The authors examined the reliability, sensitivity, and specificity of DSM-III and DSM-III-R criteria for autism in relation to each other and to clinical diagnoses in 114 children and adults (52 diagnosed by clinicians' best judgment as autistic and 62 as nonautistic but developmentally disordered). They used a standard, structured coding scheme to evaluate each patient. The reliability of specific criteria was generally high. Although DSM-III criteria were highly specific, they were less sensitive; the reverse was true for DSM-III-R. The authors conclude that the diagnostic concept of autism in DSM-III-R appears to have been substantially broadened.     

A closer look at the Autism Behavior Checklist: Discriminant validity and factor structure

The psychometric properties of the Autism Behavior Checklist (ABC; Krug, Arick, & Almond, 1980a, 1980b), a 57-item screening checklist for autism was investigated. Professional Informants completed the ABC on 67 autistic and 56 mentally retarded and learning-disabled children. The autistic children were the total population of autistic children aged 6–15 in two circumscribed suburban and rural regions. Using the total score, the ABC accurately discriminated 91% of the children, with 87% of the autistic and 96% of the nonautistic group correctly classified. Moreover, the accuracy of classification was virtually identical when only the more heavily weighted checklist items were used. A 3-factor model accounted for 32% of the total variance in the checklist. Seventeen items loaded.4 or more on Factor 1, 12 items loaded on Factor 2, and 10 items loaded on Factor 3. The present results fail to provide empirical support for a single unidimensional scale for autism. Also, there is little support for subdividing the checklist into five subscales based on symptom areas.This research was supported by grant No. 6603-1202-42 from the National Health Research and Development Program of Health and Welfare Canada to the second author and a Social Sciences and Humanities Research Council of Canada Doctoral Fellowship to the first author. We thank all of the parents and children who have contributed to this research. We also thank Isabel Smith, Julia McInnes, Margaret MacKinnon Doncaster, Mary Clark-Touesnard, Leslie Donovan, and Penny Corkum for data collection.     

The Pre-Linguistic Autism Diagnostic Observation Schedule

The Pre-Linguistic Autism Diagnostic Observation Schedule (PL-ADOS) is a semistructured observation scale designed for use as a diagnostic tool for children less than 6 years old who are not yet using phrase speech and are suspected of having autism. The PL-ADOS takes approximately 30 minutes to administer and is appropriate for use with this population because of its emphasis on playful interactions and the use of toys designed for young children. Reliability studies indicated that both individual activity ratings and summary ratings could be reliably scored from videotaped assessments by naive raters. Additionally, PL-ADOS scores of nonverbal preschool-aged children referred for clinical diagnosis and classified on the basis of a diagnostic team's clinical judgment, clearly discriminated between autistic and nonautistic developmentally disabled children. The resulting diagnostic algorithm is theoretically linked to diagnostic constructs associated with ICD-10 and DSM-IV criteria for autism.Preparation of this article was supported by National Institute of Mental Health Grant MH46865-05 and the Medical Research Council Child Psychiatry Unit in London, England. The authors gratefully acknowledge the contributions of Debra Combs, Glenna Fields, Mary Jane Elliott, Caroline Hellriegel, Susan Jaedicke, Kim Sipes, and Amelia Spencer who assisted with data collection and reliability coding; Sharon Storoschuk who assisted in data collection, reliability coding and data analysis; and Andrew Pickles who provided statistical assistance.     

Perception of complex sounds in autism: abnormal auditory cortical processing in children

OBJECTIVE: The authors have previously described less activation of left speech-related temporal areas in adults with autism when listening to speech-like sounds than in normal adults. Here, they investigated whether this abnormal cortical processing was also present in children with primary autism. METHOD: Regional cerebral blood flow was measured with positron emission tomography after premedication in 11 autistic children and six nonautistic mentally retarded children during rest and while they were listening to speech-like sounds. RESULTS: As with autistic adults, direct comparison between the two groups revealed significantly less activation in the autistic group localized in left speech-related areas. CONCLUSIONS: For the first time to their knowledge, an activation study was performed in children with autism and has confirmed previous results obtained in adults. The abnormal cortical auditory processing observed in both children and adults with autism could be involved in inadequate behavioral responses to sounds and in language impairments characteristic of autism.     

Social class distribution of fathers of children enrolled in the Iowa Autism program

The social class distribution of fathers with autistic children attending a locally well-known and state-supported modern autism program was examined and was compared to the social class distributions observed in a nonautistic, mentally retarded population, in children with other psychiatric disorders, and in the general population from which the present autistic sample was drawn. No significant differences were found among the groups. The findings supported the view that if studies are not biased by certain selection factors outside the autistic child's clinical picture and diagnosis, and if services become better known and readily available, then no differences in social class distribution between autistic and nonautistic groups occur. The results suggest that social class is not an important factor in the origin of autistic syndrome.     

Low platelet-poor plasma levels of serotonin in adult autistic patients

BACKGROUND: Hyperserotonemia has been reported in about a third of autistic patients. However, most studies have examined whole blood levels of serotonin (5-HT), the vast majority of which is found in platelets. The aim of this study was to determine 5-HT levels in platelet-poor plasma (PPP) in a group of adult patients with autism. METHODS: Levels of PPP 5-HT were compared between 10 adult drug-free autistic patients and 12 healthy controls. The Ritvo-Freeman Real-Life Rating Scale and the Overt Aggression Scale (OAS) were administered to the autistic group as a measure of symptom severity. RESULTS: Significantly lower PPP 5-HT levels were observed in the autistic group as compared to the controls (p = 0.03). In addition, PPP 5-HT levels were inversely correlated with OAS scores among subjects with autism (r = -0.64, p < 0.05). CONCLUSION: PPP 5-HT ('free') levels appear to be low in autistic patients and may play a role in the pathophysiology and symptomatology of the disorder.     

A comparison of obstetrical records of autistic and nonautistic referrals for psychoeducational evaluations

Heretofore most studies dealing with the association between perinatal complications and autism have used a normal comparison group. In this study obstetrical records of 59 autistic children were compared to those of 28 nonautistic children whose intelligence has a similar range and distribution as the autistic sample. Using an optimality score to reflect number of obstetrical complications, we found that the nonautistic controls experienced less optimal conditions than the autistic sample. Abnormal presentation at birth is the only factor that occurred more frequently for the autistic sample than control sample.We are grateful to our friends and colleagues, Sam Odom and Arthur Koch, for assistance with the statistical treatment of the data. We also acknowlege the support of Henry Schroeder, Director of the Institute for the Study of Developmental Disabilities.     

孤独症核心家系5—HT和APOE基因的关联研究

目的 探讨孤独症与5-HT基因和APOE基因之间的关系。方法 应用PCR-RFLP技术对符合国际疾病分类第10版(ICD-10)中孤独症诊断标准的21例孤独症患儿和他们的父母进行了5-HT2a,5-HT6和APOE多态性的检测。结果 孤独症患儿与对照组5-HT2a,5-HT6和APOE的基因频率和基因型频率的分布呈基本一致的趋势,两组间未显示具有统计学意义的差别。采用基于单体型的单体型相对风险率分析方法,发现仅5-HT6基因中T等位基因与孤独症显著关联(RR=3.59,P<0.05)。传递不平衡检验(TDT)发现孤独症可能与5-HT6中T等位基因相连锁(McNemarX~2=5.4,P<0.05)。结论 5-HT6基因与孤独症的发病可能存在关联或连锁关系。     

Social class factors in autism

Social class factors were studied in families of 148 patients hospitalized at the UCLA Neuropsychiatric Institute from 1961 to 1970. Seventy-four patients with the syndrome of perceptual inconstancy and diagnosis of autism were matched according to age, sex, and time of admission with 74 hospitalized for other neuropsychiatric disorders. Statistical comparisons of parental data revealed no significant differences in mean age at time of patient's birth, educational or occupational level, income, social class indexes, or distribution. Certain significant differences were noted in racial and religious compositions, and more mothers of autistic patients were unemployed at the time of their child's hospitalization. These findings, which differ from many reporting a significantly higher social class standing of families of autistic children, are discussed. It is suggested that future surveys of more culturally and socioeconomically heterogeneous populations will confirm that there is no significant association between social class factors and autism.This research was supported by grants from the National Institute of Child Health and Human Development, Grant 04612 to the Mental Retardation Center, UCLA, National Institute of Health Grant RR-3 to the Health Sciences Computer Facility, UCLA, and by the Department of Mental Hygiene, State of California. The authors wish to express their appreciation to Dr. A. Forsythe, Miss E. Bauschek, Miss Gwen Moore, and Mrs. Judy Klusza for help with statistical analyses and Miss Juli Wasserman and Mrs. Rose Weisler for administrative assistance.     

Comparison of clinical diagnoses and Rimland E2 scores in severely disturbed children

The Rimland E2 questionnaire was applied to three groups of children for whom clinical diagnoses of Infantile Autism, Autism with Associated Symptoms, and Mental Retardation had been made, as well as to normal controls. The results confirm that the Rimland scale is accurate in differentiating autistic from nonautistic children. But the scale does not appear to permit clear differentiation of infantile autism from autism with associated symptoms, and the more typical autistic children (diagnosed as Kanner's EIA) did not all yield high scores. Several possible explanations for this fact are put forward.This work was supported by Grants Nos. 80-07 (Ministry of Public Health); CNRS (ERA 697) Biological Methods in Neuropsychiatry; INSERM C.L. 79-1-422-6; DGRST, DNP 78-7-2787; and Fondation pour la Recherche Medicale S-O-C-1979. We thank coinvestigators J. L. Adrien and B. Garreau. M. L. Metais, D. Lioret, and C. Depienne assisted in technical phases of the research.     

Temporal lobe dysfunction in childhood autism: a PET study. Positron emission tomography

OBJECTIVE: The nature of the underlying brain dysfunction of childhood autism, a life-long severe developmental disorder, is not well understood. Although researchers using functional brain imaging have attempted to contribute to this debate, previous studies have failed to report consistent localized neocortical brain dysfunction. The authors reasoned that early methods may have been insensitive to such dysfunction, which may now be detectable with improved technology. METHOD: To test this hypothesis, regional cerebral blood flow was measured with positron emission tomography (PET) in 21 children with primary autism and in 10 nonautistic children with idiopathic mental retardation. Autistic and comparison groups were similar in average age and developmental quotients. The authors first searched for focal brain dysfunction in the autistic group by using a voxel-based whole brain analysis and then assessed the sensitivity of the method to detect the abnormality in individual children. An extension study was then performed in an additional group of 12 autistic children. RESULTS: The first autistic group had a highly significant hypoperfusion in both temporal lobes centered in associative auditory and adjacent multimodal cortex, which was detected in 76% of autistic children. Virtually identical results were found in the second autistic group in the extension study. CONCLUSIONS: PET and voxel-based image analysis revealed a localized dysfunction of the temporal lobes in school-aged children with idiopathic autism. Further studies will clarify the relationships between these temporal abnormalities and the perceptive, cognitive, and emotional developmental abnormalities characteristic of this disorder.     

Urbanicity-related Variation in Help-seeking and Services Utilization among Preschool-age Children with Autism in Taiwan

The present study examines urbanicity-related differences in help-seeking process among preschool children with autism and investigates the factors associated with utilization of autism-related services within the year of diagnosis. Using the 1997–2004 National Health Insurance Research Database (NHIRD) in Taiwan, we identified a total of 3495 autistic children born in 1997–1999 and 13964 matched controls. Results indicate that suburban and rural autism tended to receive the diagnosis at an older age and to have a longer diagnosis process as compared with urban counterparts. Male gender, a younger age of diagnosis, and being diagnosed by psychiatric specialty strongly predict subsequent greater utilization of autism-specific services (all p < 0.05). Health policy makers and other service providers should address the needs of children with early-onset neurodevelopmental disorders in rural areas, particularly those from disadvantaged families.     

Autistic social impairment in the siblings of children with pervasive developmental disorders

OBJECTIVE: Sibling recurrence risk in autism has been estimated to be approximately 10%. This study investigated subsyndromal autistic impairments among siblings of probands with pervasive developmental disorders. METHOD: The authors used the Social Responsiveness Scale to obtain quantitative assessments of autistic social impairment in three groups of proband-sibling pairs: 1) autistic children from multiple-incidence families and their closest in age nonautistic brothers (N=49 pairs); 2) children with any pervasive developmental disorder, including autism, and their closest-in-age brothers (N=100 pairs), and 3) children with psychopathology unrelated to autism and their closest-in-age brothers (N=45 pairs). RESULTS: Sibling Social Responsiveness Scale scores were continuously distributed and substantially elevated for both the autistic and pervasive developmental disorder groups. Highest scores (i.e., greatest impairment) were seen among siblings of autistic probands from multiple-incidence families, followed by siblings of probands with any pervasive developmental disorder, then siblings of probands with psychopathology unrelated to autism. CONCLUSIONS: Taken together with previous findings, these results support the notion that genetic susceptibility factors responsible for common, subsyndromal social impairments may be related to the causes of categorically defined pervasive developmental disorders.     

Autism and head circumference in the first year of life.

BACKGROUND: It has been reported that children with autism and pervasive developmental disorder have a significantly smaller head circumference at birth and that their head circumference then increases disproportionately rapidly in the first year of life. METHODS: We attempted to replicate these findings using 15 narrowly defined autistic children from the National Collaborative Perinatal Project and approximately 40,000 nonautistic control subjects. RESULTS: The autistic group had a slightly but not significantly larger head circumference at birth. At 4 months, the head circumference in the autistic group was not significantly larger than that of control subjects, but body weight and length were significantly larger in the autistic group. CONCLUSIONS: We believe this is the first report of significant general body growth in autistic children in infancy; the larger head circumference may be part of this excessive general growth.     

Brief report: Differences in sex ratios in autism as a function of measured intelligence

Results from analyses of sex ratios as a function of IQ are presented for 623 autistic children (487 males, 136 females) and 506 nonautistic, communication-handicapped and behavior-disordered children (374 males, 132 females). Proportionately more autistic females were found to have IQs of 34 or below than above 34. However, a linear trend of an increasing number of males with increasing intelligence was found only for nonautistic subjects. The relevance of these findings to genetic factors and the heterogeneity of autism is discussed.     

Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children

Serotonin content, serotonin uptake sites, and serotonin receptor binding measured in animal studies are all higher in the developing brain, compared with adult values, and decline before puberty. Furthermore, a disruption of synaptic connectivity in sensory cortical regions can result from experimental increase or decrease of brain serotonin before puberty. The purpose of the present study was to determine whether brain serotonin synthesis capacity is higher in children than in adults and whether there are differences in serotonin synthesis capacity between autistic and nonautistic children. Serotonin synthesis capacity was measured in autistic and nonautistic children at different ages, using alpha[11C]methyl-L-tryptophan and positron emission tomography. Global brain values for serotonin synthesis capacity (K complex) were obtained for autistic children (n = 30), their nonautistic siblings (n = 8), and epileptic children without autism (n = 16). K-complex values were plotted according to age and fitted to linear and five-parameter functions, to determine developmental changes and differences in serotonin synthesis between groups. For nonautistic children, serotonin synthesis capacity was more than 200% of adult values until the age of 5 years and then declined toward adult values. Serotonin synthesis capacity values declined at an earlier age in girls than in boys. In autistic children, serotonin synthesis capacity increased gradually between the ages of 2 years and 15 years to values 1.5 times adult normal values and showed no sex difference. Significant differences were detected between the autistic and epileptic groups and between the autistic and sibling groups for the change with age in the serotonin synthesis capacity. These data suggest that humans undergo a period of high brain serotonin synthesis capacity during childhood, and that this developmental process is disrupted in autistic children.     

A comparative study of attachment behavior in young children with autism or other psychiatric disorders

The present study examined attachment behavior in children with autism and children with other developmental or psychiatric disorders. The groups were matched on chronological and mental age, IQ, and socioeconomic status. When a modified Strange Situation paradigm was used, no group differences were found in proximity seeking, contact maintenance, proximity avoidance, or contact resistance; the groups also did not differ in their overall security ratings. Attachment security was related to several developmental variables in the autistic group but not in the nonautistic comparison group. This suggests that attachment formation may involve different processes in autistic children than in nonautistic children of equivalent intellectual level.     

Minor physical anomalies in young psychotic children

The authors examined three groups of children for minor physical anomalies: 52 autistic children, 34 nonautistic siblings of these patients, and 29 normal controls. The total number of anomalies and the weighted score were significantly higher in the autistic children. The formation of these anomalies in the first three months of fetal life may concur with the developmental deviation of the central nervous system in some of these individuals.