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Biomedical subjects

B Garreau

Publications and source records attributed to B Garreau.

At least 19 recordsLinked to original sources

Immunoreactivity of sera to a peptide derived from the serotonin 5-HT1A receptor in a group of children with developmental disorders: possible role in non-autistic epilepsy.

The presence of autoantibodies against the serotoninergic 5-HT1A receptor has been reported in serum from an autistic child using radioligand binding studies. It is now well established that, in cardiovascular diseases with an autoimmune component, patients present in their sera autoantibodies directed against the second extracellular loop of some G-protein coupled membrane receptors. We thus investigated by an enzyme-immunoassay method the presence of anti-5-HT1A receptor antibodies in sera of children with developmental disorders using synthetic peptides corresponding to the first and the second extracellular loops of this receptor. The population of children with developmental disorders was divided in autistic children with or without EEG abnormalities, and in non-autistic children with or without EEG abnormalities. We found that 6 out of 10 sera of non-autistic children with an abnormal EEG recognized the second extracellular loop of the 5-HT1A receptor. This is significantly higher than the other groups of children with developmental disorders or a healthy control group. These observations support the existence of an autoimmune component in epilepsy.

Adolescent

Bioclinical profiles of autism and other developmental disorders using a multivariate statistical approach.

To study the relationships between clinical and biological data that are necessary for physiopathological analysis in the field of developmental disorders, we developed a quantified grouping system, based on four developmental assessment parameters. Parallel with this clinical research, we developed electrophysiological procedures adapted to the pathology of autism. In this paper, we report the utilization of an original multivariate descriptive statistical approach (correspondence analysis followed by cluster analysis) that allowed us to identify different bioclinical profiles using these clinical and electrophysiological data conjointly. These profiles are believed to be evidence for different underlying cerebral dysfunctions. This procedure proved effective in identifying two main bioclinical dimensions in a population of 145 developmentally disordered children. These dimensions reflect the association of intellectual impairment and centroparietal electrophysiological reactivity on the one hand, and autistic behavior and temporal electrophysiological reactivity on the other. This study, performed on a large population of children using objective methods of data analysis, provides validation of numerous multidisciplinary studies of autism and other developmental disorders carried out on small samples of children.

Autistic Disorder

Validation of the Revised Behavior Summarized Evaluation Scale.

The Behavioral Summarized Evaluation scale (BSE), previously published and validated, was developed for the evaluation for the autistic behavior in developmentally disorder children. A revised version of this scale, the Revised Behavior Summarized Evaluation Scale (BSE-R) completed the 20-item BSE scale with the most relevant items extracted from a similar evaluation carried out with very young children. Thus 9 items were added to the original scale concerning nonverbal communication, emotional, and perception areas. This paper reports the reliability and validity studies of this new scale. In addition to confirming the previously published findings concerning the first version of the BSE, new items were extracted from the BSE-R content validity study. They involve fundamental functions such as intention and imitation which open new perspectives for a physiopathological approach to developmental disorders. The BSE-R is a useful tool for progressive recording of the evolution of patients both treated over long periods and included in short-term controlled therapeutic studies.

Autistic Disorder

Neuropathological study of a case of autistic syndrome with severe mental retardation.

Infantile autism is a syndrome of unknown aetiology and unknown neuro-anatomic substrate. The authors report a histological study of the brain of a well-documented 16-year-old female with autistic syndrome and severe mental retardation, using direct microscopic examination of the whole brain. The major findings are low brain weight, a thin corpus callosum and ventricular dilatation. No abnormalities were found in the hippocampus or cerebellum. Excessive axonal elimination during brain development is hypothesized. The relations of hypothetical developmental events with the clinical features of autistic syndrome are discussed.

Adolescent

Quantified multidimensional assessment of autism and other pervasive developmental disorders. Application for bioclinical research.

A large number of investigation techniques are used to establish the relationships between the clinical and biological data which are necessary for physiopathological analysis in the field of developmental disorders. It therefore seemed necessary to develop a quantified grouping system, based on developmental assessments, which could allow closer matching between clinical evaluations and biological numerical data. Two hundred and two subjects presenting developmental disorders (autistic disorder, pervasive developmental disorder not otherwise specified and mental retardation) were examined. For each child, a quantification of autistic behaviour, intellectual impairment, neurological signs and language and communication disorders was performed. A cluster analysis of these quantified data elicited four subgroups according to the scores obtained in these four different areas. We showed the value of this approach by applying it to one of the studies of monoamines routinely examined in childhood autism--dopamine and HVA, its main urinary derivative. Moreover, this method revealed a subgroup within the total population which was independent of nosographic classification and which had a particular clinical and biochemical profile. Other applications could follow, for example in the fields of neurophysiology, cerebral imaging, molecular biology and genetics.

3,4-Dihydroxyphenylacetic Acid

Identification of behaviour profiles with a population of autistic children using multivariate statistical methods.

The Revised Behaviour Summarized Evaluation Scale (BSE-R) was developed for the objective evaluation of autistic behaviours in order to facilitate the recording of the evolution of developmentally disabled children. Among its 29 items, 13 items that precisely describe the degree of autistic behaviours were extracted by Principal Component Analysis. We hypothesised that these relevant behaviours could differentiate autistic behaviour profiles in a population of children previously diagnosed as typically autistic. For this purpose, we used an original multivariate descriptive statistical approach, Correspondence Analysis, which can help in detecting structural relationships among variables. In a population of autistic children initially diagnosed using DSM-III-R criteria, this procedure proved effective in identifying new main dimensions of behaviours among the 13 previously defined core autistic symptoms. Cluster analysis, which followed factorial analysis, allowed the identification of three meaningful behaviour profiles separated principally on the basis of two main functions, perception and imitation, which have been always considered to be fundamentally involved in autistic syndrome. The individualisation of homogeneous subgroups of children on the basis of the behavioural evaluation provides a potentially useful starting point for further biological and therapeutic studies.

Autistic Disorder

Disorders of regulation of cognitive activity in autistic children.

Infantile autism is a pervasive developmental disorder characterized by disturbances concerning not only the areas of socialization and communication ("aloneness") but also the ability to modify and change behavior ("need for sameness"). In most recent studies, various abnormal and deviant cognitive activities, such as the ability to regulate one's behavior, were considered as accounting for these signs. In this report, we examined the regulation of cognitive activity, from a developmental perspective in comparing autistic with mentally retarded children matched in a pairwise manner by global, verbal, and nonverbal developmental ages. All children were tested with tasks adapted from the Object Permanence Test which corresponds to Piaget's sensorimotor development Stages IV to VI. Results showed that autistic children had a pervasive difficulty in maintenance set, made more perseverative errors when the abstraction degree of task was higher, and were more variable in their behavioral strategies. Discussion is focused on the interests and limits of these tasks for the examination of regulation activity from diagnostic and developmental perspectives. Finally, interpretations about recent neuropsychological and neurophysiological works, and additional interdisciplinary studies are suggested.

Attention

Delayed maturation of the frontal cortex in childhood autism.

OBJECTIVE: The authors investigated the metabolic maturation of the frontal cortex in pre-school autistic children. METHOD: Regional cerebral blood flow (CBF) in five children with primary autism diagnosed according to the DSM-III-R criteria was studied longitudinally. Regional CBF in each of the autistic children was measured with single photon emission computed tomography twice during their development: at the age of 3-4 years and 3 years later. At each stage, the autistic children were compared to an age-matched comparison group of five nonautistic children with normal development. RESULTS: A transient frontal hypoperfusion was found in the autistic children at ages 3-4 years; this corresponded to the pattern of perfusion observed in much younger normal children. By the ages of 6-7, the autistic children's frontal perfusion had attained normal values. CONCLUSIONS: Since CBF patterns in children are related to maturational changes in brain function, these results indicate a delayed frontal maturation in childhood autism. Such a delayed brain maturational process is consistent with the clinical data and cognitive performance of autistic children.

Adolescent

Auditory stimulus intensity responses and frontal midline theta rhythm.

The influence of stimulus intensity on the N1 component of auditory evoked potentials recorded at fronto-central sites was investigated in respect to the spectral components of the EEG recorded at Cz, Fz and Oz. The study was performed on 14 healthy adult subjects. The only EEG frequency bandwidth that was strongly correlated with the N1 amplitude-intensity slope was the theta rhythm, particularly the 5-7 Hz frequencies recorded at Cz and Fz. This frequency bandwidth corresponds to the previously described frontal midline theta rhythm related to performance of tests that require continuous concentration of attention. Our results show that the steeper the slope, the greater the amount of Fm theta. This suggests that the interindividual differences in the N1 amplitude/intensity slope could be related to interindividual differences in attentional readiness toward the auditory stimuli, even when delivered in "passive" conditions.

Adult

The complexity of dopamine receptors and psychopharmacotherapy in children.

The efficacy of dopaminergic antagonists, which are neuroleptics, has been shown in children in varied clinical situations. Five dopaminergic receptors (D1, D2, D3, D4, D5) have thus far been cloned: their existence has thus been confirmed, but their functional significance remains to be determined. This publication reviews their main characteristics. The multiplicity of cerebral dopamine receptors is consistent with the future development of new, more selective and discriminating psychotropic drugs. The diversity of interactions of dopaminergic receptors, among themselves and with receptors for other neurotransmitters, however, explains the difficulty in understanding the mechanism of action of neuroleptics and defining their more rational use in children.

Adolescent

Theoretical aspects of the study of benzodiazepine receptors in infantile autism.

This paper is part of a special section on 'psychopharmacotherapy in children' and focuses on benzodiazepine receptors in autism. Infantile autism in an early and pervasive developmental disorder described by Kanner in 1943. Anatomical, pathological and magnetic resonance imaging studies have indicated changes in the cerebellum and hippocampus of autistic subjects. Given the numerical importance and diffuse benzodiazepine receptors, their study by functional brain imaging methods in vivo could be value in cases of infantile autism as a gauge of neuronal potentiality. The main data concerning benzodiazepine complex are presented. The relations between these data and the neurophysiological hypotheses of autism are discussed.

Adolescent

Dopaminergic D2 receptor SPECT imaging in Rett syndrome: increase of specific binding in striatum.

A dopamine deficiency has been implicated in Rett syndrome, a progressive encephalopathy in girls that involves movement, tonus and cognitive disorders. To test the hypothesis that striatal D2 receptors increase in number in early stages of the disease, we measured the binding potential of 123I-Iodolisuride, a specific D2 ligand, in eleven Rett children aged 4-15 yr (7.9 +/- 3.5 yr) (mean +/- s.d.) and eight control subjects aged 3.5-13 yr (8.1 +/- 3.8 yr) who exhibited other neurological disorders. Regional cerebral blood flow (rCBF) was also measured with SPECT using 133Xe. The binding potential for 123I-ILIS and D2 receptors was significantly higher in Rett (0.45) than in controls (0.23) (p < 0.01). An increase in 123I-ILIS binding due to increased rCBF in patients' striata was excluded. Our results are consistent with a higher density of D2 receptors in young patients suffering from Rett syndrome because of reduced dopaminergic neurotransmission.

Adolescent

Blood flow response to auditory stimulations in normal, mentally retarded, and autistic children: a preliminary transcranial Doppler ultrasonographic study of the middle cerebral arteries.

Using the noninvasive transcranial ultrasonic Doppler method, flow dynamics of the middle cerebral arteries were investigated in relation to auditory stimulations in 12 children with autistic behavior compared with 12 normal controls and 10 mentally retarded children. In normal children, auditory stimulation evoked lateralized modifications: blood flow increased and resistance index decreased on the left side; such modifications were not recorded on the right side. This pattern should indicate vasodilatation mechanisms induced by changes in the metabolism of the brain areas supplied by the left middle cerebral arteries (MCA). Although less asymmetrical, this pattern was also found in the mentally retarded children. Autistic children significantly differed from these two groups. They displayed a symmetric pattern of responses with a blood flow decrease and resistance-index increase on both sides; this could suggest abnormal metabolic mechanisms induced by auditory stimulation in autistic children and could be related to the previous hypothesis of impairment in the development of cerebral lateralization in autism. These preliminary results show that transcranial Doppler ultrasonography may be a valuable and practicable tool for the noninvasive study of evoked blood flow responses in psychopathology.

Arousal

Unimodal and crossmodal reactivity in autism: presence of auditory evoked responses and effect of the repetition of auditory stimuli.

Using auditory evoked responses, this work compares the reactivities to unimodal and crossmodal stimuli and the main neurocognitive functions most often disturbed in autism. With the aim of testing the hypothesis that the deficit in the ability to form crossmodal associations in autism is linked to a cognitive abnormality, auditory evoked responses to simple and to crossmodal (auditivo-visual) stimuli were recorded in 30 autistic children and compared with those of 30 normal and 30 mentally retarded children. Relationships between electrophysiological reactivity and neurocognitive functions showed that the cognitive deficit in the ability to maintain crossmodal associations is preceded by a more elementary perceptive abnormality in autistic children.

Acoustic Stimulation

Sensitivity and specificity of the Behavioral Summarized Evaluation (BSE) for the assessment of autistic behaviors.

The Behavior Summarized Evaluation (BSE), developed for the assessment of autistic behavior, was specifically designed to evaluate the severity of behavioral problems in autistic children involved in bioclinical and therapeutic studies. The reliability studies and the factorial analysis of this scale have been previously published. The present paper examines the effectiveness of the BSE to discriminate 58 autistic from 58 nonautistic mentally retarded children. The BSE clearly separated the two samples of children. A most efficient combination of 8 items emerged from the stepwise item selection procedure. The between-group differences were highest on 4 items, indicating that the most particular pattern in autistic compared to nonautistic children could be the association of autistic withdrawal and stereotypic behaviors. Our findings suggest that the BSE could help in the detection and evaluation of autistic developmental deviance. Implications for further research are discussed.

Autistic Disorder

Electrophysiological evidence of different abilities to form cross-modal associations in children with autistic behavior.

This study evaluates the amplitudes of auditory evoked responses and the variability of evoked responses, using a signal-to-noise ratio (SNR) method applied to individual evoked potential in a cross-modal (sound and light) association paradigm in 17 children with autistic behavior matched for sex and chronological age with normal children. Auditory evoked responses were smaller in children with autistic behavior than in normal children. The modifications of amplitudes and of SNR during cross-modal associations allowed the separation of children with autistic behavior into 3 subgroups who presented different patterns of ability to form cross-modal associations. These 3 subgroups of children presented different clinical profiles demonstrating that the differences observed in the ability to form cross-modal associations can be related to differences in the main psychophysiological functions such as attention, intention, motility, association, contact and communication.

Acoustic Stimulation

[Development in the metabolism of dopamine and its derivatives. Application to gross development disorders].

Dopamine (DA) and its metabolites homovanillic acid (HVA) in total, free and conjugated forms, dihydroxyphenylacetic acid (DOPAC) in total, free and conjugated forms, and 3 methoxytyramine (3 MT) levels were determined in the urine of autistic children from 2 years 8 months to 12 years of age and compared to those in normal children of identical age. Very significant group and age effects were found for DA, HVA and 3 MT. In the discussion, results are related to the hypothesis of a disorder in the maturation of the dopaminergic systems in infantile autism.

3,4-Dihydroxyphenylacetic Acid