Catecholamines metabolism in infantile autism: A controlled study of 22 autistic children

In a group of 22 autistic children aged 5 to 16 years and a group of normal controls matched for age and sex, catecholamines metabolism was investigated in plasma, platelets, and urine. This investigation was part of a research project in which several biological parameters (including serotonin) were explored simultaneously in the same children. In the autistic group, epinephrine and norepinephrine were significantly elevated in plasma, while epinephrine, norepinephrine, and dopamine were significantly lower in isolated platelets. No significant difference was found between the two groups for the urinary excretion of epinephrine, norepinephrine, dopamine, DOPAC, and MHPG. Other differences between the two groups in the statistical correlations of several biochemical parameters also suggest abnormalities of bioamine metabolism in the platelets of autistic children.This work was supported by a grant of the Institut National de la Santé et de la Recherche Médicale (INSERM-ATP n 73.79.105). We are indebted to Prof. M. Da Prada, Pharmaceutical Research Department, Hoffman-La Roche, Basel, for his continuous help throughout this work, and to Ms. D. Pasques, Hôpital Saint-Louis, Paris, for her excellent technical assistance.     

A follow-up study of high-functioning autistic children

It is well known that IQ is an important prognostic variable in the outcome of autistic children. There are, however, very few data available on the outcome of nonretarded autistic children as adults. We identified 16 such probands from records and followed them up between 11 and 27 years since discharge from a center specializing in the assessment of autistic children. There were 12 males and 4 females, average age was 26, and mean IQ was 92 (range 68–110). Although the majority were functioning poorly in terms of occupational-social outcome and psychiatric symptoms, a surprising number (4) had a very good outcome and might be considered recovered. The severity of early autistic behavior was a poor predictor of outcome, but neuropsychologic measures of nonverbal problem solving were highly correlated with outcomes. The results of the study indicate that a small percentage of nonretarded autistic children can be expected to recover to a substantial degree.We are very grateful to the staff of the West End Creche, Toronto, Ontario for all their help in conducting this study. Special thands must go to Dr. Milada Havelkova, without whose support and assistance the study could not have been completed. The project was funded by the Medical Research Council of Canada, and Dr. Szatmari was supported by the Council under the Fellowship program.     

Lithium and chlorpromazine: A controlled crossover study of hyperactive severely disturbed young children

A controlled crossover study of lithium and chlorpromazine involving 10 severely disturbed children, 3 to 6 years of age, of which 6 were schizophrenic and 1 autistic, is reported in detail. Patients were matched for motor activity (hyper- and hypoactivity) and prognosis. More symptoms diminished on chlorpromazine than on lithium. However, improvements were only slight on both, except in one child whose autoaggressiveness and explosiveness practically ceased on lithium (nonblind evaluations). Blind ratings indicated no statistically significant difference between the two drugs as well as absence of statistically significant change from baseline to treatment with either. Lithium diminished the severity of individual symptoms, though not statistically significant, such as explosiveness, hyperactivity, aggressiveness, and psychotic speech. Its effect in adult schizophrenia is compared to responses of schizophrenic children. Also discussed is the relationship of EEG to clinical improvement and toxicity, and effect of lithium on hyperactivity and aggressiveness. It is suggested that lithium may prove of some value in treatment of severe psychiatric disorders in childhood involving aggressiveness, explosive affect and hyperactivity.This study was supported in part by Public Health Service Grant MH-04665 from the National Institute of Mental Health and in part by a grant from the Harriett Ames Charitable Trust. The authors wish to thank Dr. Sam Gershon for his valuable comments and suggestions, and Ms. M. Kalmijn, R. Bensimhon, H. Von Hedrich, L. Levidow, and P. Mikel for technical assistance.New York City Health Research Council Career Scientist I-470.     

Serotonin metabolism and other biochemical parameters in infantile autism. A controlled study of 22 autistic children

The serotonin metabolism was extensively studied in 22 couples of autistic children and age- and sex-matched controls. Histamine, calcium, and uric acid were also measured in urine and whole blood or plasma. Autistics and controls did not differ in histamine, and only minor changes were noticed in calcium content. According to previous reports, serotonin levels were often, but not always, elevated in the blood of autistic children. Based on data including urinary serotonin and 5-hydroxyindoleacetic acid, platelet serotonin uptake and efflux, platelet monoamine oxidase and glutathione peroxidase activities, and uric acid and plasma tryptophan, the origin(s) of such hyperserotonemia in autism appear(s) to be of metabolic origin, i.e., a decreased catabolism and/or an increased biosynthesis of serotonin.     

Neurophysiological study of autistic children

Two different hypotheses have been proposed on the pathophysiology of infantile autism; a caudally directed pathological influence originating in telencephalic structure, and a rostrally directed pathological influence originating in brainstem and diencephalic structure. This paper described results of neurophysiologic research of infantile autism: (1) cortical evoked potentials, (2) autoregressive spectral analysis of EEG, (3) brainstem lesions on ABR and vestibular study by Ornitz E M (1985) and (4) cognitive functioning by Novick (1980) and Niwa (1983). Those studies suggest that the brainstem, including the vestibular nuclei, and related nonspecific thalamic centers, can be the primary loci of the system dysfunction in autism.     

The effect of high doses of vitamin B6 on autistic children: a double-blind crossover study.

The authors used data from an earlier nonblind study to identify 16 autistic-type child outpatients who had apparently improved when given vitamin B6 (pyridoxine). In a double-blind study each child's B6 supplement was replaced during two separate experimental trial periods with either a B6 supplement or a matched placebo. Behavior was rated as deteriorating significantly during the B6 withdrawal.     

Dermatoglyphic study in autistic children and controls

Dermatoglyphic patterns formed during fetal development reflect genetic or early developmental events. These patterns might provide a means for investigation of a biological basis for autism, but the results of prior studies are not conclusive. The authors undertook a study of 95 autistic children, defined by DSM-III criteria ascertained independently by three child psychiatrists. The dermatoglyphic patterns of these children were compared with several control groups, all age-matched, separated by sex, and comprising different ethnic compositions. Analysis of variance as well as chi-square methods of statistical analysis were applied. Consistency among hands, ATD angle values, total ridge counts, incidence and effects on ridge count of arches, double loops, and whorls were evaluated in this comparatively large, well-controlled group of autistic children, and all failed to support a value for dermatoglyphic analysis as a discriminant of autism.     

Long-term follow-up study of 13 autistic children

This is a report concerning 13 autistic children who have been followed up from their early infancy to adulthood. Some intake variables, such as speech development at the age of 5, were correlated with the outcome status. As a result, we showed that a higher level of speech development at age 5 did not necessarily lead to a better outcome in social adaptability. We showed also that any of the variables we examined, such as the presence of brain organic abnormality, the duration of schooling and the duration of medical treatment, were not factors in determining a good or poor prognosis. We concluded that a rather poor outcome seen in our subjects might be due to the particular situation in Japan throughout this study period, and not a reflection of the real natural history of early infantile autism.     

A longitudinal study of joint attention and language development in autistic children

This study was designed to examine the degree to which individual differences in gestural joint attention skills predicted language development among autistic children. A group of 15 autistic children (mean CA=45 months) were matched with one group of mentally retarded (MR) children on mental age and another group of MR children on language age. These groups were administered the Early Social-Communication Scales. The latter provided measures of gestural requesting, joint attention, and social behaviors. The results indicated that, even when controlling for language level, mental age, or IQ, autistic children displayed deficits in gestural joint attention skills on two testing sessions that were 13 months apart. Furthermore, the measure of gestural nonverbal joint attention was a significant predictor of language development in the autistic sample. Other variables, including initial language level and IQ were not significant predictors of language development in this sample.This study was supported by NIMH grant 30530 and NINCDS grant 30527.     

The development of normal and autistic children: A comparative study

This study tests the hypothesis that the development of normal and autistic children differs only in rate and asymptote. A total of 195 normal children between 1 and 5 years of age, 160 normal children between 3 months and 24 months of age, and 41 autistic children between 5 and 11 years of age were evaluated on the eight psychological variables constituting the Behavioral Rating Instrument for Autistic and other Atypical Children (BRIAAC). While many similarities were found, there were a sufficient number of differences to justify DSM-III's statement that certain autistic behaviors are not normal at any stage of development. Differences were particularly prominent when the development of normal infants was compared with that of severely disturbed autistic children. In general, the issue of whether deviant development differs only quantitatively from normal development can best be decided on the basis of developmental data and by utilizing instruments that sample all the major characteristics of both populations.     

A preliminary fMRI study of moral judgment task in high functioning autistic children

Autistic patients show social cognitive disorders and hardly recognize their situations. This means it is difficult for them to obey rules or conform to customs. Humans have social intelligence thought to be related to a network connected to amygdala, the orbito-frontal cortex, and the superior temporal gyrus. It has been reported that normal participants judged morality in dilemma sentences through which the medial orbito-frontal cortex and the right lateral prefrontal cortex were activated. However, where autism is concerned, there has been no fMRI study during the moral judgment task. The study herein showed changes of autistic brain areas related to moral judgment. This study included one high-functioning autistic child, one Asperger's syndrome child, and three normal children. Pictures of social situations were painted and the children present were asked to judge whether the contents were moral or immoral. The results of fMRI demonstrated the orbito-frontal cortex was active in normal children but not active in the autistic children with regard to moral judgment. This suggested autistic people have functional disorders in this area. BA11 and BA22 were activated in the control group and these areas are thought to be related to sociality and "theory of mind". Furthermore, BA38 was activated in one control and this area is also related to "theory of mind" and emotions. Moral judgments about personal affairs activate brain areas related to emotions (bilateral medial frontal gyri, bilateral cingulated gyri and bilateral angular gyri) and moral judgments about public affairs activate brain areas related to working memory (left medial frontal gyrus and bilateral temporal cortices). Based on the results above, we think moral judgment is related to "theory of mind" and social cognition, and shares a common sense processing mechanism. Recently Greene et al. reported that the prefrontal cortex was active during moral judgment in an fMRI study of normally developed people. Their result reinforces our results.     

Social adjustment and placement of autistic children in Middlesex: A follow-up study

A follow-up study of 32 autistic children identified in an epidemiological survey when they were 8 to 10 years of age and investigated 8 years later at 16 to 18 years of age is presented and discussed. Outcome is described in terms of general social adjustment, employment, and placement history. Results are contrasted with those for a comparison group identified in the original survey and those reported for comparably defined children in other studies. Only one autistic child was employed, and outcome was in general worse for the autistic group in which 62% required extensive care and supervision. There does not seem to be a direct relationship between employability and amount of schooling. Expectations with respect to outcome can be indicated with some confidence for comparable groups.This paper is based on research supported by a grant MH20537 awarded by the National Institute of Mental Health.     

Response to triiodothyronine and dextroamphetamine: A study of preschool schizophrenic children

A controlled study of triiodothyronine (T₃), a hormone with CNS effects and stimulating properties, is reported in detail and discussed. Twelve of the 16 subjects (13 boys and 3 girls ranging in age from 3 to 6 years) were psychotic (10 schizophrenic and 2 autistic), 2 had chronic organic brain syndromes (Turner's and Klinefelter's, both with withdrawing reaction) and 2 were nonpsychotic (withdrawing and hyperkinetic reactions). Optimal daily doses of T₃ ranged from 12.5 to 75 mcg, while those of dextroamphetamine, used as control, from 1.25 to 10 mg. Nonblind evaluations indicated marked improvement on T₃ in 11 children, slight in 3, and deterioration in one. Blind ratings indicated statistically significant improvement in overall symptomatology (p0.01). While dextroamphetamine yielded poor responses in all diagnostic categories, T₃ had antipsychotic and stimulating effects. T₃ is viewed as an agent that is potentially effective in the treatment of childhood schizophrenia.This study was supported in part by Public Health Service Grant MH-04665 from the National Institute of Mental Health and in part by a grant from the Harriett Ames Charitable Trust.     

Behavior therapy for autistic children: A study of acceptability and outcome

An inpatient program for autistic children which used behavior modification methods is described, and a follow-up study of the first 15 children discharged from the program is reported. In general, the outcome results appear to be comparable to those of other treatment methods. A second main purpose of the study was to assess the acceptability of this program to parents and to document their impressions regarding their child's period of inpatient care. Overall, a high level of acceptability was found.     

Self-recognition in autistic children

The hypothesis that the autistic child's impairment in social relatedness stems in part from underlying deficits in self-recognition was explored. Fifteen autistic children ranging from 4 to 6 years of age were assessed for visual self-recognition ability, as well as for skills in two cognitive areas that are believed to be related to the development of self-recognition — object permanence and gestural imitation. It was found that 13 of 15 autistic children showed evidence of self-recognition. The two autistic children who lacked self-recognition were the only two children to perform poorly on the object permanence tasks, which suggests that these two cognitive domains may be closely linked in development. In contrast, there appeared to be no consistent relationship between motor imitation ability and self-recognition. It was concluded that the autistic child's social deficits are not due to a basic lack of differentiation between self and other. This research was funded by the University of North Carolina Research Council. Part of the data presented here were from Fawn McKissick's undergraduate honors thesis from the University of North Carolina at Chapel Hill. We express our sincere appreciation to the autistic children who participated in the study, and to their parents, and to the staff of the TEACCH Division, Department of Psychiatry, University of North Carolina, for their assistance and cooperation. We would also like to thank several persons for their help in data collecting and coding: Karen Cotten, Pete Giordano, Vickie Hall, Lee Hendrix, Shari Jernigan, Kevin Lumley, Cindy Seagroves, Sheryl Solomon, Kathy Stetson, and Jeannie Teasley. Mary Lynn Eckert provided editorial and secretarial support. Dr. Robert Cairns made helpful comments on this paper.     

A comparative dermatoglyphic study of autistic,retarded, and normal children

Dermatoglyphic comparisons were made among 32 autistic children aged from 4–10 to 18–11; sex-, age-, and IQ-matched retarded children; and sex- and age-matched normal children. Significant differences were found between the autistic and normal children for distribution of dermal patterns and ridge line disruption, but no significant differences were found for the total mean ridge counts or mean ridge count rankings. Apart from the right hand of the autistic children, there were no unusual scores for digital dispersion ratios. Autistic and retarded children differed only in their distribution of dermal patterns, with the autistic children apparently intermediate between retarded and normal groups. These results indicate that conclusions of unique congenital disturbance in the etiology of autism inferred from different dermatoglyphics may be premature, and that dermatoglyphics may be ineffective in delineating autistic children from other atypical populations.Our thanks are due to Mr. Allen of the Vern-Barnett Diagnostic Teaching Centre (Autistic Children's Association of New South Wales); Mrs. Pearce of Evandale School for Specific Purposes (S.S.P.); Mrs. Ford of Sydenham-Bankstown S.S.P.; Mr. Higgins of Chalmers Road S.S.P.; Mr. Edmunds of Caroline Chisolm S.S.P.; Mr. Craig of Oatley West Primary School; Mr. Brook of Randwick Boys' High School; and Sergeant Dodds of the Training, Information and Research Section, Central Fingerprint Bureau of Australia. Their co-operation and assistance, especially in providing the subjects and equipment used in this study, are greatly appreciated.     

Handedness in autistic children

A test of handedness in a sample of 20 autistic children and 25 normal children revealed marked differences. The frequency of non-right-handedness in normal children was 12%, whereas it was 65% in autistic children. The significance of this difference for the etiology of autism is discussed.     

Sleep in children with autistic spectrum disorder: A questionnaire and polysomnographic study

ObjectiveTo evaluate sleep in children with autistic spectrum disorder (ASD) by means of sleep questionnaires and polysomnography; moreover, to analyze their cyclic alternating pattern (CAP).MethodsThirty-one patients with ASD (28 males, 3 females, aged 3.7–19 years) and age-matched normal controls were included. ASD children were evaluated by a standard sleep questionnaire that consisted of 45 items in a Likert-type scale covering several areas of sleep disorders and by overnight polysomnography in the sleep laboratory after one adaptation night.ResultsThe questionnaire results showed that parents of ASD children reported a high prevalence of disorders of initiating and maintaining sleep, enuresis, repetitive behavior when falling asleep, and daytime sleepiness. Polysomnographically, ASD children showed reduced time in bed, total sleep time, sleep period time and rapid eye movement (REM) latency. ASD subjects had a CAP rate during slow-wave sleep (SWS) lower than normal controls, together with a lower percentage of A1 subtypes.ConclusionsASD children questionnaires showed a higher percentage of disorders of initiating and maintaining sleep than normal controls; this was not completely confirmed by sleep staging. CAP measures showed subtle alterations of NREM sleep which could be detected with an appropriate methodology of analysis. The reduction of A1 subtypes during SWS might play a role in the impairment of cognitive functioning in these subjects.