Peter E. Tanguay

Autism and Tuberous Sclerosis

Autism is a behavior disorder with genetic influences indicated from twin and family studies and from the cooccurrence of autism with known genetic disorders. Tuberous sclerosis complex (TSC) is a known genetic disorder with behavioral manifestations including autism. A literature review of these two disorders substantiates a significant association of autism and TSC with 17–58% of TSC subjects manifesting autism and 0.4–3% of autistic subjects having TSC. In initial data collected on 13 TSC probands and 14 autistic probands in our family study of autism and TSC, we identified 7 TSC subjects with autism. The seven TSC autistic probands are similar to non-TSC autistic probands on the Social and Communication domains of the Autism Diagnostic Inventory (ADI) (Le Couteur et al., 1989), but show fewer Repetitive Rituals. There are more male TSC probands with autism than female, despite an equal sex ratio among TSC probands. The TSC probands with autism have significantly more seizures and mental retardation than those without autism; however, the extent and etiology of associations require further study. Our preliminary findings suggest that a fruitful approach for delineating genetic influences in autism may come from further investigation of possible mechanisms underlying the association of autism and TSC.

Pervasive Developmental Disorders: A 10-Year Review

OBJECTIVE To summarize recent advances about the nature, diagnosis, and treatment of pervasive developmental disorders. METHOD Review of Medline databases, books, and book chapters published between July 1989 and November 1999. RESULTS Clinical and genetic studies support expansion of the concept of autism to include a broader spectrum of social communication handicaps. The prevalence of autism is approximately 1 per 2,000; the prevalence of autism and Aspergers disorder together is 1 per 1,000. The Checklist for Autism in Toddlers is a useful screening instrument for 18-month-old children; the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule are instruments of choice for research. Although twin and family studies clearly support genetic factors as important in autism, linkage analysis studies indicate that many genes may be involved. There is no one treatment of choice. Social-pragmatic approaches, augmented by individualized strategies and social coaching, may be best for teaching social communication skills. Pharmacological interventions have a limited role in improving social communication, but selective serotonin reuptake inhibitors and atypical neuroleptic medications may help ameliorate aggression, hyperactivity, and other secondary problems. CONCLUSIONS Private and government agencies must continue to support basic and applied research.

Autism in Tuberous Sclerosis Complex

The frequency and clinical presentation of autism in 28 probands with tuberous sclerosis complex (TSC) are reported and risk factors that may influence the development of autism in TSC are examined. Eight probands meet ICD-10 and DSM-IV criteria for autism, an additional 4 meet criteria for pervasive developmental disorder (PDD). Twelve TSC probands with autism/PDD are compared to 16 TSC probands without these conditions for factors which may underlie the association of autism and TSC. A specific seizure type, infantile spasms, as well as mental retardation, are increased in the TSC, autistic/PDD group. Furthermore, rates of social phobia and substance abuse are elevated among first-degree relatives of TSC probands with autism compared to first-degree relatives of TSC probands without autism. Implications of these findings in understanding the association of autism and TSC are discussed.

The Kiddie Formal Thought Disorder Rating Scale: clinical assessment, reliability, and validity.

The Kiddie Formal Thought Disorder Story Game and the Kiddie Formal Thought Disorder Scale were administered to schizophrenic, schizotypal, and normal children, aged 5 to 13 years. The story game elicited more elaborate speech samples than did a structural clinical interview focused on psychotic symptomatology. The sum of illogical thinking and loose associations was a reliable kappa = 0.77), sensitive (79%), and specific (90%) indicator of schizophrenia in this sample. It also demonstrated significant developmental changes in the schizophrenic and normal subjects. Incoherence and poverty of content of speech were infrequently rated in both schizophrenic and normal subjects.

Rapid eye movement (REM) activity in normal and autistic children during REM sleep.

Thirty normal children (aged 3–68 months) and 16 autistic children (aged 36–62 months) were recorded during nonmedicated sleep and data pertaining to rapid eye movements (REM) were measured during the first three REM periods of the night. When time of night from which data were gathered was held constant, normal children showed a significant relationship between age and the organization of eye movements into discrete bursts. When autistic children were compared to age-matched normal controls, they showed an immaturity in this phenomena, their results being similar to those found in children less than 18 months of age. Such an immaturity could result from dysfunction at a number of diverse levels and sites in the central nervous system.

Developmental dyslexia: Electrophysiological evidence of clinical subgroups☆

Abstract Event-related potentials (ERPs) to word and to musical-chord stimuli were recorded in 13 dyslexic boys and 13 age-matched normal readers. Normal readers and dyslexics whose reading handicaps involved visual-spatial processing deficits had greater word versus musical-chord ERP waveform differences over the left as compared to the right hemisphere. Dyslexics whose reading difficulties were related to auditory-verbal processing deficits did not exhibit this asymmetry. These results are interpreted as supportive of the hypothesis that the latter group of dyslexics has failed to develop normal left hemisphere specialization for processing of auditory-linguistic material.

Evolution of sleep spindles in childhood

Twenty-six normal children (age range range 4-68 months) were studied during Stage 2 sleep which occurred within 20 min preceding or following the first three REM periods of the night. Sleep spindles were measured in Fp1T3. The number, length, and percent of sleep spindle activity were found to be maximal at 46 months of age. Beyond 6 months spindle activity decreased to reach minimal values by 27 months, remained fairly constant to 54 months, then rose again to higher values in the oldest subjects. The mean spindle-wave frequency was 1314 c/sec in subjects younger than 40 months, but was 12-13 c/sec in older subjects. Spindle onsets in Fp1T3 and Fp2T4 were more often concurrent in older as compared to younger subjects. Auditory stimulation (binaural clicks, 60 dB above hearing threshold) affected neither the incidence nor the length of spindles during sleep. Because sizable changes in sleep spindle activity are found between 3 months and 5 years of age, and because such changes are relatively consistent between subjects, it is concluded that sleep spindles recorded between frontal and temporal areas may serve as a useful index of neural maturation in the human subject.

Parental reproductive problems and gestational hormonal exposure in autistic and schizophrenic children.

The incidence of infertility and two or more spontaneous abortions was significantly increased in the parents, compared to that reported for the general population, in this pilot survey of 61 patients evaluated for major childhood psychoses. In addition, 18% of our patients had a history of early gestational exposure to progesterone/estrogen compounds (9 patients) and to cortisone (2 patients). This frequency of gestational hormonė exposure was significantly increased over that in normal infants from three published surveys. However, in 5 of the 11 patients with gestational hormonal exposure, the medication was prescribed because of prior parental reproductive problems or bleeding during the current pregnancy. Therefore, it cannot be concluded that the gestational hormonal exposure was causally related to the psychoses present in these patients. In order to obtain more conclusive data, there will need to be continued monitoring of parental reproductive histories and gestational environmental exposures in autistic and schizophrenic children.

Hemisphere and ear asymmetry in the auditory evoked response to musical chord stimuli

The human averaged auditory evoked response (AER) to monaurally presented musical chord stimuli was recorded simultaneously from electrodes placed symmetrically over the two cerebral hemispheres at central and Wernicke (W) scalp locations. Stimulus presentation was quasi-random to the left (L) and right (R) ears of 14 normal-hearing right-handed male university students. The mean integrated amplitude over the initial 300 msec of the AER reflected asymmetries at the W locations as a function of hemisphere derivation and ear stimulated. The major interhemispheric difference observed when effects of contralateral auditory pathway-to-cortex projections had been equated was a significantly greater magnitude integrated amplitude response at the right (W2) scalp site to L-ear stimulation in comparison with the AER at the left (W1) cortical location to Rear stimulation. Differences of AERs between hemispheres summed across both ears stimulated conceived as attributable to additive auditory input showed a significantly greater integrated amplitude value at W2. When effects of contralateral auditory pathway predominance were examined, the AER integrated amplitude from W2 exceeded the hemisphere response at W1 to L-ear stimulation. The demonstrated asymmetries in the evoked response to musical chords may be associated with preponderance of the right hemisphere and saliency of the L ear for nonverbal, nonmeaningful auditory stimuli.

Electrophysiological studies of autism: the whisper of the bang.

Many neurophysiological hypotheses have focused upon the level of the central nervous system at which abnormal neural function may be present. Although some have argued that the type of language and cognitive defects shown by autistic children almost certainly reflects forebrain dysfunctions, current studies point to the possibility that some autistic children may have dysfunction of neural systems in the brainstem. One interpretation of these findings is that such abnormalities, occurring during a critical phase of early postnatal development, might themselves have acted directly as neuropathological agents, adversely influencing developing forebrain systems. A model for such an event has already been identified in animal research. If this be true, neurobiologists may not necessarily be identifying what is current pathology but may only be seeing a reflection of abnormal neural factors that once were important in development of the syndrome. Such a possibility suggests that investigators should consider extending their current studies to include young normal children as well as children with prototypic signs of abnormal language and interpersonal development.