Dopamine-beta-hydroxylase (DBH) and homovanillic acid (HVA) in autistic children

In the present study, plasma DBH activity and urinary HVA levels were measured in 19 autistic and 15 normal children. DBH activity was significantly elevated in the 8 less retarded autistic patients. In this subgroup, a negative correlation was found between plasma DBH and urinary HVA levels. These results support the hypothesis of a possible involvement of brain catecholamine dysfunction in the production of autistic symptoms.This study was supported by C.N.R.S. (UA 596) Biology and Neuropsychiatry, Sécurité Sociale 1982 and Fondation Langlois. We wish to thank Mrs. Barré, Mrs. Lehn, and Miss Lioret for their technical work.     

Lack of correlation between DST results and urinary MHPG in depressed inpatients

Summary Abnormalities of noradrenaline metabolism and of the activity of hypothalamic-pituitary adrenal axis (HPA) have been reported in depression. To study the possible relationship between these 2 parameters, urinary excretion of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and Dexamethasone Suppression Test (DST) were analyzed in 58 depressed patients. A positive correlation was found between the age of depressed patients and 24-h urinary excretion of MHPG. Twenty-two patients (38%) were DST non suppressors. Pre-DST plasma cortisol levels were significantly higher in non suppressors than suppressors. No difference was found however between urinary MHPG levels in supressors and non suppressors. There was no correlation between pre-DST plasma cortisol and levels of urinary excretion of MHPG. These results do not support the hypothesis of a relationship between these 2 parameters. However, when depressed patients were separated into two groups according to urinary excretion of MHPG (high MHPG and low MHPG), the high MHPG group included significantly more non suppressors then the low MHPG one. This result is not sufficient to demonstrate of link between HPA system activity and central noradrenaline metabolism.     

Monoamines (norepinephrine,dopamine, serotonin) in the rat medial vestibular nucleus: endogenous levels and turnover

Summary Monoamine (norepinephrine, dopamine, serotonin) and metabolite endogenous levels were determined in the rat medial vestibular nucleus (MVN) using HPLC with electrochemical detection. As a comparison, the locus cruleus (LC) and dorsal raphe nucleus (RD) which contain the cell bodies of MVN noradrenergic and serotoninergic neurons respectively were also analyzed. Norepinephrine (NE) and serotonin (5-HT) basal levels of MVN were high (33.8 and 39.2pmol/mg protein respectively) but lesser than in LC or RD. Great amounts of MHPG and 5-HIAA were also present in the MVN. The turnover of NE assessed both from the ratio MHPG/NE and by the decrease in the NE content after treatment with -methylparatyrosine was faster in the MVN (half-life 1.5h) than in LC (half-life 3.6h). On the other hand, the ratio 5-HIAA/5-HT was lower in the MVN (0.58) than in the RD (0.85) indicating a smaller 5-HT turnover in the MVN. In addition, like LC and RD, the MVN contained meaningful amounts of dopamine (DA) and DOPAC. The high ratio DA/NE (0.27) suggests the presence of non precursor specific dopaminergic pools. However, individualized dopaminergic neurons have not yet been demonstrated. The data are discussed in line with the possible neurotransmitter function of monoamines in the MVN.     

Biochemical investigations into the alcoholic delirium: Alterations of biogenic amines

Summary In eight male patients with alcoholic delirium concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovannilic acid (HVA) in CSF, activity of dopamine--hydroxylase (DBH), and urinary excretion of noradrenaline (NA), adrenaline (A), and dopamine (DA) were measured during the delirium and a drug-free control period.MHPG concentration in CSF, excretion of NA and A as well as activity of serum DBH were significantly elevated during the delirium phase as compared to the control period. Urinary DA excretion and HVA in CSF did not show any constant changes. There was a positive correlation (r=0.64) between DBH activity and the intensity of the delirium (as measured on the delirium rating scale).It is hypothesized that there is a relationship between alcoholic delirium and increased central noradrenergic activity.Parts of this study were presented at the Sixth International Institute on the Prevention and treatment of Drug Dependence (Hamburg, June 28–July 2, 1976)     

Corrective socialization in foster care of children

While the phrase, interminable foster care is becoming a damning cliché in the dialogues of juvenile courts and child welfare organizations, many children are growing up in foster homes. Human love must move us to approve and enrich these foster families; childhood is too brief and important to be knowingly allowed disapproved or impoverished experience. This paper describes the foster situation: families, children, and the involved professionals. It then presents a teachable developmental theory weaved from threads of numerous known theories, and describes a process whereby interminable foster experience was used therapeutically for a group of handicapped homeless children.     

Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia

Summary A unique model of DA system regulation is presented, in which tonic steady-state DA levels in the ECF act to down-regulate the response of the system to pulsatile DA released by DA cell action potential generation. This type of regulation is similar in many respects to the phenomenon proposed to mediate the action of norepinephrine on target neurons; i.e., an increase in the signal-to-noise ratio as measured by postsynaptic cell firing (Freedman et al., 1977; Woodward et al., 1979). However, in this model the signal and the noise are neurochemical rather than electrophysiological. Furthermore, the noise (tonic DA in the ECF) actually down-regulates the signal (phasic DA release) directly, and thereby provides a signal of its own that affects the system over a longer time-course. Therefore, the difference between signal and noise may also depend on the time frame under which such determinations are made.     

Conductive hearing loss in autistic,learning-disabled,and normal children

Katz (1978) has suggested that mild, fluctuating conductive hearing loss due to middle-ear anomalies may account for the language and attention problems of learning-disabled children. His position was extended here to include autism. Normal, learning-disabled, and autistic children received repeated impedance measures over 5 weeks. A repeated-measures ANOVA of central tendency and variablility values led to the conclusions that (1) fluctuating, negative middle-ear pressure greater than normal characterizes both autistic and learning-disabled children, (2) the negative pressure is greater in autistic than in learning-disabled children, and (3) the condition is typically bilateral for autistic children.This research, project title Language and Sensory Stimulation in Autistic Children, was made possible by a grant from the National Institutes of Mental Health (No. MH37035-02).     

Single drug therapy for intractable epilepsy

Summary Single drug therapy with either phenytoin or primidone resulted in complete seizure control in 11 of 35 patients (31%) referred to an epilepsy clinic for treatment of uncontrolled chronic epilepsy with complex-partial seizures. Complete seizure control was associated with an increase in the mean plasma concentrations from 14 g/ml to 23 g/ml phenytoin and from 34 g/ml to 40 g/ml phenobarbitone with no change in the antiepileptic drug. Insufficiently low plasma concentrations of less than 11 g/ml phenytoin or phenobarbitone were measured at the first visit in 14 patients (40%). Non-compliance was admitted by eight patients (23%). Optimum single drug therapy is of considerable clinical value in intractable epilepsy with complex-partial seizures.

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Zusammenfassung Eine Monotherapie mit Phenytoin oder Primidon führte zur Anfallsfreiheit bei 11 von 35 Patienten (31%), die wegen schwerbehandelbarer psychomotorischer Anfälle eine Epilepsieambulanz aufsuchten. Anfallsfreiheit trat auf bei einem Anstieg der mittleren Plasmakonzentration von 14 g/ml auf 23 g/ml Phenytoin und von 34 g/ml auf 40 g/ml Phenobarbital. Ein Wechsel der Medikamente war nicht notwendig. Während der ersten Untersuchung wurden bei 14 Patienten (40%) zu niedrige Plasmakonzentrationen von weniger als 11 g/ml Phenytoin oder Phenobarbital gefunden. 8 Patienten (23%) gaben eine unregelmäßige Einnahme der Medikamente (non-compliance) zu. Eine konsequente Monotherapie ist von klinischem Wert für die Behandlung von schwerbehandelbaren Epilepsien mit psychomotorischen Anfällen.

     

Positive practice overcorrection combined with additional procedures to teach signed words to an autistic child

The present study evaluated the effectiveness of using positive practice over-correction in combination with other techniques to teach two manual signs (milk and cookie) to an autistic boy. This boy had a great deal of difficulty informing any type of discrimination and often became confused in learning the most simple simultaneous discrimination. Intervention primarily consisted of positive practice overcorrection in which the subject was physically guided to form a required hand sign 10 times when he responded incorrectly and was positively reinforced when he signed correctly. The study used a changing criterion within a multiple-baseline design across responses. The results indicated that overcorrection plus positive reinforcement was effective in teaching one sign (milk), however, and added contingent exercise (having to stand up and sit down 10 times for an incorrect response) was required to teach the second sign (cookie). Once the two signs were learned to a criterion level, it was a relatively easy task for the subject to respond correctly with the signs in a matching-to-sample task.     

Die spektralphotometrische Analyse des Liquor cerebrospinalis im UV-Licht

Zusammenfassung Die spektralphotometrische Bestimmung der Absorptionskurve des natürlichen Liquors im UV-Licht gestattet in exakt reproduzierbarer Weise normale und pathologische Liquores zu unterscheiden. Dies ist namentlich bei Verlaufskontrollen von Bedeutung. Ein konstantes Absorptionsmaximum (A) findet sich im kurzwelligen Bereich bis 240 m und ist zur quantitativen Eiweißbestimmung mit einer für die klinischen Bedürfnisse hinreichenden Genauigkeit geeignet. Eine von den quantitativen Eiweißwerten unabhängige Absorptionsbande ( A) hat ihr Maximum bei allen normalen und den meisten pathologischen Liquors bei 266 m Eine Verschiebung nach 275 m kommt vereinzelt bei pathologischen Liquores vor.Eine starke A mit einem Durchlaßgrad von weniger als 30% spricht auch bei im übrigen normalen Liquorwerten für pathologische Veränderungen.Das mittels Perchlorsäure gefällte Liquoreiweiß zeigt in alkalischer Lösung ein dem Grade nach von dem Eiweißgehalt abhängiges Absorptionsmaximum bei 215 m und eine flache Absorptionsbande zwischen 275–285 m.     

Effect ofd,l-α-aminoadipate on the mediobasal hypothalamus and endocrine function in the rat

Summary Using the glutamate analog,d,l--aminoadipic acid (d,l-AA), experiments were conducted to examine the nature, extent, and specificity of its toxicity in the mediobasal hypothalamus and to determine its effect on endocrine homeostasis. Neonatal rats received daily injections ofd,l-AA (4 g/kg BW) on postnatal days 5–10 and were killed at various post-treatment intervals. Sex-matched littermates were given equimolar amounts of NaCl and served as controls. Treated rats killed 18 days post injection weighed slightly less than controls and had reduced testicular, ovarian, and uterine weights, but the differences were not statistically significant. Ind,l-AA treated rats serum and pituitary levels of TSH and PRL were comparable to control values. Pituitary content of LH ('s and 's) and FSH ('s), however, was lower (P<0.05) ind,l-AA treated rats than in controls, but serum levels were not significantly different. Distinct cytopathologic changes were evident in the arcuate nucleus and median eminence ofd,l-AA-treated rats killed at 2 and 6 h post injection only. By 12 h evidence of acute damage had largely disappeared. Both glial and ependymal cells underwent edematous swelling and necrosis, but neurons were largely unaffected. Evidence of reactive changes, such as gliosis, infiltration of microglia, and removal of debris, however, were not very conspicious. A random sample of mediobasal hypothalami of rats killed 18 days post injection failed to show any detectable lesion or residual effects of earlier pathology. Age at the time of exposure to the gliotoxin was found to be an important variable affecting both extent and duration of injury. The most deleterious effects were observed when the gliotoxin was administered in the form of a single injection on postnatal day 5 only. The results suggest that normal neuronal activity and endocrine homeostasis, specifically gonadotropin, may be irreversibly altered as a consequence of transient disruption of the glial compartment.Supported by grants from the Medical Research Council of Canada, the St. Boniface General Hospital, and Mrs. James A. Richardson Research Foundations     

Birth Patterns in Mentally Retarded Autistic Patients

Some studies claim to have shown that, compared to the general population, autistic children are born more often in the spring. The current study sought to replicate this finding in a large Dutch sample of mentally retarded autistic patients. Birth data for 1,031 patients with a diagnosis of Infantile Austism or other psychoses with origin specific to childhood were compared to those of the Dutch national population. Separate analyses were performed on diagnostic subgroups (i.e., infantile autism vs. other psychoses with origin specific to childhood), gender, and intelligence. No evidence was found to suggest that autism is characterized by a deviant birth pattern.     

Ultrastructure of peripheral nerve in metachromatic leucodystrophy

Summary An electron microscopical study of two consecutive nerve biopsies from a patient with metachromatic leucodystrophy (sulphatide lipidosis) was made. The ultrastructural changes observed consisted of: a) irregular whorls of myelin. The myelin in the whorls showed a thickened, sometimes doubled, intraperiod line, which was barely visible in compact myelin; b) inclusion bodies up to 1 in diameter in the cytoplasm of Schwann cells. These had a lamellar structure, with stacked membranes 60 Å apart; c) a loose pattern of the myelin in some nerve fibers, with loss of the intraperiod line, and d) presence of abnormally dense mitochondria with thickened cristae in Schwann cells. It is suggested that: a) the whorl formation and the ultrastructural abnormalities of the myelin in the whorls may be due to impaired myelin synthesis, and b) that the inclusion bodies may represent the accumulation of cerebroside sulfate in micellar aggregates. The loose pattern of myelin is considered artifactural until proven otherwise.

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Zusammenfassung Zwei aufeinanderfolgende Nervenbiopsien bei einem Patienten mit metachromatischer Leukodystrophie (Sulfatid-Lipoidose) wurden elektronenoptisch untersucht. Die beobachteten ultrastrukturellen Veränderungen bestehen in: a) unregelmäßigen Wirbelbildungen (whorls), in welchen das Myelin Verdickungen, manchmal Verdopplung des Zwischenstreifens (intraperiod line) aufweist, was im kompakten Myelin kaum sichtbar ist. b) Einschlußkörperchen mit einem Durchmesser bis zu1 im Cytoplasma der Schwann-Zellen. Diese weisen lamelläre Struktur mit einem Membranabstand von 60 Å auf. c) ein lockeres (loose) Myelinmuster mit Verlust des Zwischenstreifens in einigen Nervenfasern und d) Auftreten von abnorm dichten Mitochondrien mit verdicktem Cristae in Schwann-Zellen. Es wird angenommen, daß a) die Wirbelbildungen und die ultrastrukturellen Myelinabnormitäten in den Wirbeln einer gestörten Myelinsynthese entsprechen und b) daß die Einschlußkörperchen die Anhäufung von Cerebrosidsulfat in micellaren Verbänden darstellen. Das lockere Myelinmuster wird vorläufig als artifiziell angesehen.

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This investigation was supported in part by Public Health Service Research Grant No. FR-86 from the N.I.H. Division of Research Facilities and Resources.     

Motion and Emotion: A Novel Approach to the Study of Face Processing by Young Autistic Children

The specificity of facial processing impairment in autistic children, particularly in the domain of emotion, is still debated. The aim of our study was to assess the influence of motion on facial expression recognition in young autistic children. Thirteen autistic children (M age: 69.38 months) were matched for gender and developmental level with a control group of 13 normal children (M age: 40.53 months). They were compared on their ability to match videotaped still, dynamic, and strobe emotional and nonemotional facial expressions with photographs. Results indicate that children with autism do not perform significantly worse than their controls in any of our experimental conditions. Compared to previous studies showing lower performance in autistic than in control children when presented with static faces, our data suggest that slow dynamic presentations facilitate facial expression recognition by autistic children. This result could be of interest to parents and specialists involved in education and reeducation of these children.     

HVA and MHPG in urine of premature infants

Higher levels of homovanillic acid (HVA) and 3-methoxy-4- hydroxyphenylglycol (MHPG) were observed in urines of 12 premature infants than in older children. An examination of the influence of age, sex, size, and head circumference revealed that the smaller the infants, the higher the HVA and MHPG values. Recently several investigators have reported an increased titer of urinary HVA in autistic children. It has been hypothesized that the increased levels of catecholamine metabolites (notably HVA and MHPG) could reflect accelerated catecholamine turnover. The elevated urinary HVA titers in infants as well as in autistic children may be due to an immaturity of the dopaminergic receptors.     

Motor imitation abilities and neurological signs in autistic children

Autistic children were compared with chronological and mental agematched normal children on two tests of motor imitation and on the Herzig Battery for Non-Focal Neurological Signs. The results indicated that autistic children have significant handicaps in the neurodevelopmental area, with very poor performance on motor imitation tasks and a universal and significant excess of soft signs of neurological dysfunction. Such dyspraxias may underlie the failure of these chlidren to learn to use gesture.     

Phospholipids of the cerebrospinal fluid in the course of subacute sclerosing leukoencephalitis

Summary Phospholipid fractions and total phospholipids were examined in the cerebrospinal fluid of a 6-year-old girl suffering from subacute sclerosing leukoencephalitis. The examination was repeated in monthly intervals over a period of 5 months. Total phospholipids were found to be considerably higher than in control patients of about the same age. During the time of observation we found an inverse relationship between lecithin and lysolecithin and between cephalin and lysocephalin.List of Abbreviations CSF Cerebrospinal fluid - EEG Electroencephalogram (-graphy) - PEG Pneumencephalogram (-graphy) - SSLE Subacute sclerosing leukoencephalitis - PL Phospholipid(s) - PLP Phospholipid phosphorus - O Origin - LL Lysolecithin - SM Sphingomyelin - L Lecithin - LC Lysocephalin (including lysophosphatidylethanolamine, lysophosphatidylserine and lysophosphatidylinositol) - C Cephalin (including phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine) - Pl Phosphatidylinositol - PS Phosphatidylserine - PE Phosphatidylethanolamine     

“Sporadic” prealbumin-related amyloid polyneuropathy: report of two cases

Summary Two sporadic cases of amyloid polyneuropathy are reported. There was no family history or plasma cell dyscrasia. Both showed sensorimotor and autonomic polyneuropathy with onset in the seventh decade. Amyloid deposits in both cases reacted with anti-human prealbumin sera but not with antisera to human AA and anti-human immunoglobulin light-chain amyloids, including A and A. One patient had the abnormal serum prealbumin and abnormal DNA sequence found in type I familial amyloid polyneuropathy (FAP) (Japanese type). Investigations in sporadic amyloid polyneuropathy should include immunohistochemistry, using antisera to the different amyloid proteins, and the radioimmunoassay and recombinant DNA techniques for diagnosis of FAP.     

Pathological gambling in two patients on dopamine replacement therapy for Parkinson’s disease

Abstract. We describe two cases where increases in dopaminergic therapy were initiated by the patients due to perceived deterioration in symptoms of idiopathic Parkinsons disease. Shortly afterwards, both cases also met clinical criteria for pathological gambling. To date, only 29 cases of pathological gambling in patients with Parkinsons disease have been reported. This pathological gambling disorder is an addiction-like behavior triggered by excessive dopaminergic drugs and does not respond to standard therapy for pathological gambling. It only responds to an adjustment of Parkinsons disease therapy.     

Comparison of the effects of dopamine D 1 and D 2 receptor antagonists on rat striatal,limbic and nigral dopamine synthesis and utilisation

Summary The effects of dopamine (DA) antagonists upon DA synthesis and utilisation in the rat striatum, olfactory tubercle and substantia nigra have been studied. The concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the rate of depletion of DA afterin vivo inhibition of tyrosine hydroxylase by H 44/68, and the accumulation of L-DOPA afterin vivo inhibition of 1-aromatic amino acid decarboxylase by NSD 1015 were measured in the study. Haloperidol (0.23mol/kg i. p.), sulpiride (293mol/kg i. p.) and remoxipride (5.6mol/kg i. p.) increased both DA synthesis and utilisation in the striatum and olfactory tubercle. A lower dose of sulpiride (45mol/kg i. p.) increased DA synthesis and utilisation in the olfactory tubercle alone. None of the compounds, at the doses used, affected either DOPAC and HVA concentrations or the rate of utilisation of DA in the substantia nigra. Sulpiride (293mol/kg i. p.) and remoxipride, however, produced a modest rise in nigral DA synthesis. The dopamine D 1-selective antagonist SCH 23390 had only modest effects on striatal, limbic and nigral DA synthesis and utilisation at the doses tested (0.078 and 0.36mol/kg i. p.).