On the association of fragile X with autism.
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Biomedical subjects
Publications and source records attributed to I L Cohen.
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A heat moisture exchanger (HME) with bacterial filtering capabilities was evaluated over an 8-month period in a total of 170 ICU patients. During this time there were 15 endotracheal tube (ETT) occlusions in 15 patients. Over the ensuing 4 months, cascade humidification was used for 81 patients and only one ETT occlusion occurred (p less than .01). The HMEs were replaced frequently with cascade humidifiers during the evaluation period because of inadequate airway humidification. The increase in ETT occlusion was associated with an increased incidence of pneumonia (p less than .001) and atelectasis (p less than .01). Most patients with ETT occlusion required minute volumes greater than 10 L and F10(2) greater than 0.4. We conclude that HMEs do not provide sufficient airway humidification for generalized ICU use. Their role outside of the operating room remains to be determined.
Preference for social gaze as well as the percentage occurrence of social gaze, nonverbal social avoidance, and nonverbal repetitive behaviors were examined in autistic and nonautistic prepubertal males with the fragile X syndrome (fra[X]) during social interaction with a parent or stranger. Comparison groups were nonhandicapped, Down syndrome, atypical pervasive developmental disorder, and autistic males. The subjects with fra(X) and the nonhandicapped and Down syndrome control subjects discriminated parent from stranger as evidenced by their avoidance behavior. The overall percentage of avoidance was higher, however, for both parent and stranger, among the males with fra(X). Autistic and atypical groups without fra(X) failed to discriminate parent from stranger in their avoidance behavior. Possible explanations for these group differences in terms of language level or degree of language demand were ruled out. Implications for research concerning the relations among fra(X), autism, and mental retardation were discussed.
The discovery of the Fragile X (fra(X] syndrome represents a major advance in our understanding of mild mental retardation. This X-linked syndrome is the most common hereditary form of mental retardation. Recent estimates find that approximately 1/981 males and 1/677 females carry the fra(X) chromosome. The majority of affected males are moderate to severely retarded, but about 20% are mildly retarded and about 5% are borderline. Approximately 20% of males who inherit the fra(X) chromosome are termed non-penetrant; they do not express it cytogenetically and are of normal intellect. About 1/3 of carrier females show mental impairment and about 10% are mildly retarded. We have found evidence for genetic heterogeneity based on linkage analysis to flanking DNA probes. Some large families show tight linkage between fra(X) and the flanking probe F9, while others show loose linkage. Preliminary findings indicate the linkage heterogeneity may also be related to cognition: affected males in tightly linked families tended to be mildly retarded.
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The fragile X chromosome is an important factor in inherited mental retardation in males. It has also been reported that infantile autism is associated with fragile X. Recently, an article reported an examination of a small sample of autistic children in whom the fragile X chromosome was not found. Its authors concluded that if an association between fragile X and autism exists, it is infrequent. In the present study of 144 autistic male subjects, 18 were found to have the fragile X chromosome, supporting other (epidemiological) findings that the association between fragile X and autism occurs relatively frequently.
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Two brothers with fra(X) positive X-linked mental retardation (XLMR) were treated with folic acid. Initially a double blind cross-over design was employed followed by a long-term high dose trial. A decrease in the frequency of fra(X) positive cells was observed when low folic acid culture medium was used but not when an FUdR induction system was employed. Selected behavioral characteristics improved in both while receiving folic acid. Decreased hyperactivity, greater attention span, increased motor coordination, increased quantity and quality of speech were noted. Improvement in Leiter mental age and regression after cessation of treatment was seen in one subject but not in the other. Further controlled trials with larger numbers of subjects using high doses of folic acid over longer periods of time are needed to assess the possible benefits of this experimental form of treatment.
A forward chaining conditioning procedure was used to establish an independent, appropriate response to a fire alarm in a blind, profoundly retarded adult male. The appropriate response, as defined by New York State regulations, is to exit from the residence or move to a fire-safe area within 21/2 min with minimal verbal or physical prompts. Independent responding was established within a total training time of 21/2 hr. Total time to exit was 28.5 sec.
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A comparison of the effects of lithium, haloperidol, and placebo on cognition is reported for a sample of hospitalized school-age children with a behavioral profile of aggressiveness and explosiveness. In this double-blind study, patients were randomly assigned to one of three treatment conditions. The cognitive battery was administered at the end of a 2-week placebo baseline period and again after 4 weeks of treatment. It included a simple reaction time (RT) task with preparatory intervals of 1, 4, and 8 seconds, the Porteus Mazes, and the Matching Familiar Figures Test. Drug effects on cognition, when found, were mild. Slower and more variable RTs were found on the RT task in the haloperidol group (mean dose, 3.1 mg/day), particularly at the 4- and 8-second preparatory intervals in comparison to placebo. This appeared to reflect decreased ability to hold a preparatory set. No other effects of haloperidol on cognitive performance were found. Lithium carbonate (mean dose, 1150 mg/day) caused a deterioration in qualitative performance on the Porteus Maze Test when compared with haloperidol but had no effect on test quotient scores or on the other cognitive measures. Results are discussed in terms of dose effects and the influences of task demands. This is part of a study critically assessing the effects of lithium and haloperidol on behavioral symptoms and other parameters.
An overview of research involving pharmacotherapy in infantile autism is presented. Methodological issues relating to experimental design, rating instruments and ecological factors are considered. Classification of infantile autism and diagnostic problems are discussed. Research investigations conducted in order to define diagnostic subgroups in the etiologically heterogeneous population of autistic children are described. An attempt is made to relate biochemical findings to clinical drug response. Recent findings are presented indicating that a potent neuroleptic is able to yield simultaneously significant decrease of behavioural symptoms and improved learning under both clinical and laboratory conditions. The drug can be effective in conservative doses and administered over a period of 14 weeks without untoward effects. New research plans are introduced where attentional learning will be assessed in an operant conditioning paradigm using automated procedures.
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