Sex differences in pervasive developmental disorders

Neonatal size is an important factor in determining the survivorship of infants within the first month of life. Because maternal size has an influence on neonatal size, selection should operate on those characters correlated with birth weight and gestational age, including maternal prepregnancy weight, height, and age. In the present study we use a path-analysis approach to examine the operation of selection on both neonatal and maternal size. We found that neonatal survivorship depends not only on the size of the infant at birth but also on a negative allometric relationship between the size of the neonate and the size of the mother. Thus, although the size of the mother has no direct effect on neonatal mortality, the mothers of surviving infants tend to be smaller relative to the size of their neonate. This may provide a mechanism whereby selection maintains a balance between maternal size and neonate size.     

Lead intoxication in children with pervasive developmental disorders

Ten clinical isolated strains of Human cytomegalovirus (HCMV) were obtained from 73 urine specimens of different people. Isolations from urine were carried out in human embryolung fibroblasts. Viral isolates were passaged four times. HCMV DNAs of laboratory strain AD169 and 10 clinical isolated strains were extracted with Hirt method, digested with each of the restriction enzymes EcoRI, Hind II. Comparison of restriction fragment length polymorphism (RFLP) of AD169 and isolated strains were made by hybridizing digested DNA with 32P labeled with HCMV Hind II cloned subgenomic fragments as the probe (pCM1035, pCM1015). pCM1035 is located in the joining region between the long(L) and short (S) unique sequences of the virus (L-S junction) pCM1015 is located in the terminal sequences of the virus. The results showed the genomic high degree of homology existed among all strains and the variable restriction site was in the L-S junction and terminal portion. The RFLP patterns of the clinical isolates which did not have relation in epidemiology were different, but the patterns of clinical isolates related in epidemiology were quite similar. Polymorphism frequently occurred in this case of EcoRI digested fragment hybridized with the probe of pCM1035. Southern hybridization of HCMV isolations is useful to researches into the molecular epidemiology and pathogenesis of HCMV infection.     

Hemispheric function in developmental language disorders and high-level autism

Two groups of children with contrasting types of developmental language disorder (phonologic-syntactic and semantic-pragmatic) were compared with a group of children with high-level autism and with a control group of normal children on a broad battery of neuropsychological tests, known to be sensitive to left-right hemisphere damage. Significant differences found between the groups suggest contrasting forms of hemispheric dysfunction.     

Use of risperidone in pervasive developmental disorders: a case series

A series of 14 children and adolescents (ages 9-17 years, 10 males) were treated with risperidone for pervasive developmental disorder. The rationale for using an atypical neuroleptic agent is based on its ability to target both positive and negative symptoms of schizophrenia. It was postulated that symptoms similar to the positive and negative symptoms of schizophrenia may be observed in the pervasive developmental disorders and might respond favorably to risperidone. Twelve of the 14 youths had been treated previously with several psychotropic drugs, often concurrently. Risperidone was initiated at a starting dose of 0.25 mg twice daily and increased in 0.25 mg/day increments every 5-7 days. Optimal dosages ranged from 0.75 to 1.5 mg daily in divided doses. Thirteen of the 14 youths appeared to benefit from risperidone. Improvement in functionality on the Children's Global Assessment Scale was demonstrated in 13 of 14 cases. Disruptive behaviors, when present, markedly decreased on risperidone. Ten patients showed a marked reduction in agitation and anxiety. Social awareness improved markedly in 10 patients, moderately in 3, and only slightly in 1. All but 1 patient demonstrated a lessening in obsessional behaviors. Effects on attention were uniformly positive. Side effects were minimal at the dosages used in this study; 5 patients had initial sedation. Neither extrapyramidal side effects nor agitation was observed in any case. Ten of 14 youths could be managed with risperidone monotherapy. During the follow-up period (mean 7 months), none of the patients experienced a major relapse while taking risperidone. Positive and negative symptoms, as typically characterized in schizophrenia, were both found to improve equally well with risperidone treatment. Based on these findings, a prospective clinical trial with a randomized controlled design is warranted.     

Empirically derived subtypes of pervasive developmental disorders: a cluster analytic study

A cluster analytic study was conducted to empirically derive behaviorally homogeneous subtypes of pervasive developmental disorders (PDD). Subjects were clustered based on a broad range of behavioral symptoms which characterize autism. Behavioral variables were measured using several of the standardized psychometric instruments most commonly employed in assessing autistic individuals. The cluster solution indicated the presence of four distinct groups. Validity checks generally confirmed significant between-group differences on independent measures of social, language, and stereotyped behaviors. In addition, the four-group cluster solution was compared to previously developed typological systems of PDD (i.e., subcategories based on IQ early onset, styles of social interaction, and DSM-III-R diagnosis). Results generally supported both the behavioral homogeneity of the four subgroups and also several important between-group differences. The potential utility of using cluster analyses to explore subtypes of PDD is discussed.     

Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective open-label study

OBJECTIVE: To investigate the short-term safety and efficacy of risperidone in the treatment of children and adolescents with pervasive developmental disorders. METHOD: This was a 12-week, prospective, systematic, open-label trial that included 18 subjects (15 boys and 3 girls) with a mean age of 10.2 +/- 3.7 years. The sample included 11 subjects with autistic disorder, 3 with Asperger's disorder, 1 with childhood disintegrative disorder, and 3 with pervasive developmental disorder not otherwise specified. Fourteen subjects had comorbid mental retardation. Behavioral ratings were obtained during two baseline visits and again after 12 weeks of risperidone treatment. RESULTS: The optimal dose of risperidone for the 18 subjects was 1.8 +/- 1.0 mg/day. On the basis of the global improvement item of the Clinical Global Impression Scale, 12 of 18 subjects were considered responders. Significant improvement was seen in measures of interfering repetitive behavior, aggression and impulsivity, and some elements of impaired social relatedness. The most common side effect was weight gain (range 10 to 35 lb). CONCLUSIONS: These preliminary results suggest that risperidone may be effective for improving interfering behavioral symptoms in some children and adolescents with pervasive developmental disorders. Double-blind, placebo-controlled studies are needed before definitive statements of safety and efficacy can be made.     

Chromosomal disorders and autism

Two major risk factors for late-onset familial and sporadic Alzheimer disease (AD), a leading cause of dementia worldwide, are increasing age and inheritance of the epsilon4 allele of the apolipoprotein E gene (APOE4). Several isoform-specific effects of apoE have been proposed; however, the mechanisms by which apoE isoforms influence the pathogenesis of AD are unknown. Also associated with AD is increased lipid peroxidation in the regions of the brain most damaged by disease. 4-hydroxynonenal (HNE), the most potent neurotoxic product of lipid peroxidation, is thought to be deleterious to cells through reactions with protein nucleophiles. We tested the hypothesis that accumulation of the most common forms of HNE-protein adducts, borohydride-reducible adducts, is associated with AD and examined whether there was a relationship to APOE. Our results demonstrated that reducible HNE adducts were increased in the hippocampus, entorhinal cortex, and temporal cortex of patients with AD. Furthermore, our data showed that the pattern of reducible HNE adduct accumulation was related to APOE genotype; AD patients homozygous for APOE4 had pyramidal neuron cytoplasmic accumulation of reducible HNE adducts, while AD APOE3 homozygotes had both pyramidal neuron and astrocyte accumulation of reducible HNE adducts. This is in contrast to our previous observations that a distinct HNE protein adduct, the pyrrole adduct, accumulates on neurofibrillary tangles in AD patients. We conclude that APOE genotype influences the cellular distribution of increased reducible HNE adduct accumulation in AD.     

Parental recognition of developmental abnormalities in autism

Administration of carrageenan (CA; 0.5 mg) to the plantar tissue of rats resulted in reversible inflammatory injury. The edema was monitored by changes in paw volume using a plethysmometer. Simultaneous administration of CA and nifedipine, intraperitoneally, at different doses (10, 20 and 50 mg/kg) prevented the inflammatory action, and the effect was dose- and time-dependent. In order to improve the nifedipine effects, we prepared liposomed nifedipine which, administered intraperitoneally, showed a greater anti-inflammatory action. In the presence of the L-type channel agonist Bay K 8644, the inflammation produced by CA increased and it was counteracted by free or liposomed nifedipine. The significance of these findings with respect to the mechanism of the anti-inflammatory action of nifedipine is discussed.     

Risperidone in children and adolescents with pervasive developmental disorder: pilot trial and follow-up

Dopamine receptor antagonists, particularly haloperidol, have been the most effective medications in currently available double-blind placebo-controlled studies for treating the disruptive behaviors often associated with pervasive developmental disorder (PDD). The rationale for trying risperidone in this population includes its dopamine-blocking activity; its seemingly lower incidence of tardive dyskinesia when compared to standard neuroleptics; the possibility that risperidone may ameliorate the social withdrawal of PDD, as it does the negative symptoms in schizophrenia; and substantial effects on serotonergic neurotransmission, which has been shown to be dysregulated in some patients with PDD. This study was an open-label pilot trial of risperidone in 6 subjects (aged 7-14 years, mean = 10.7) who met DSM-III-R criteria for a PDD diagnosis. The mean optimal dose was 2.7 mg daily (range 1-6). Mean duration of risperidone administration was 5.2 months (range 1-8). Despite the small sample size, risperidone treatment appeared to be associated with significant improvements in ratings of angry affect (p = 0.04) and lability of affect (p = 0.03) and with a trend (p = 0.10) toward a reduction of mean hyperactivity scores. Clinical Global Improvement scale ratings were statistically significant (p < 0.001). Increased sociability was reported in 3 subjects by their parents and family following the study. Three patients continued on risperidone for over 2 years, and none showed any loss of its apparent therapeutic effects. Weight gain was observed in 5 of 6 patients, with a median increase of 5.4 kg (12 lbs) in 7 weeks. Other side effects included transient sedation, increased salivation, and stereotypies. One child showed a worsening of pre-existing tic and phobic symptoms after 5 months of successful monotherapy. No loss of therapeutic effect was noted in the 3 subjects who remained on risperidone for over 2 years, but 1 patient developed hepatotoxicity and another developed withdrawal dyskinesia, similar to her prior experience with haloperidol. Overall, 5 of the 6 patients derived significant clinical benefits from risperidone. Pharmacologic alternatives for treating behavioral symptoms in PDD are need, and risperidone may be a promising possibility.     

Timing of social gaze behavior in children with a pervasive developmental disorder

This study compares the outcomes of two groups of 12-to-13 year olds who were in their last year at a day or five-day residential treatment center for seriously emotionally troubled children. One group was enrolled in a treatment-based program; the second group participated in a school-based program designed to ease the transition to new placements. Each group was evaluated when discharged from the center and 6 weeks after entering their new placements. Interviews with parents and teachers indicated that the school-based children scored significantly higher on six of eight indicators of adjustment than did children in the treatment-based program.     

Genetic counseling and interdisciplinary management of retinoblastoma

The rare childhood malignancy retinoblastoma (Rb) serves as one of the most important models in modern cancer genetics, since the study of its familial and sporadic occurrence has lead to the identification of the first so-called tumor suppressor gene. The nature of the Rb-predisposition and its mode of transmission could also hold true for many other familial cancers. An important goal of medical care is prevention, either by preventing the manifestation of retinoblastoma and of secondary malignancies related to the same predisposition or of their reaching an advanced stage of exacerbation. This can only be achieved by the close collaboration of several medical specialists. The human geneticist can contribute by offering genetic counselling, including risk estimates for offsprings of affected individuals, and by the molecular estimation of the Rb-trait.     

Psychopathology in children and adolescents with developmental disorders

Children and adolescents with developmental disorders suffer from a wide range of psychopathology. However, there are no published studies examining this subject exclusively in this population using recent diagnostic criteria. The primary purpose of this paper is to report on the diagnosis encountered in a clinical setting using DSM-III-R. The medical records of all individuals assessed in a specialized program during a 1-year period were reviewed looking at their demographic features, diagnoses, and target behaviors. Our sample consisted of 233 subjects and contained significantly more boys than girls. The most common psychiatric diagnoses were oppositional defiant disorder and attention deficit hyperactivity disorder. Pica, organic mental disorder NOS, and Autistic Disorder were more often encountered in individuals with low intellectual functioning. Depressive disorders, posttraumatic stress disorder, and developmental speech/language disorders were diagnosed more in high functioning subjects. The most common symptom was impulsivity. This retrospective study highlights the need for more rigorous examination of current diagnostic concepts and criteria in children and adolescents with developmental disorders. Prospective studies should be conducted with standardized instruments in clinics and community samples to provide more information on psychiatric disorders in this population.     

Differentiating attention-deficit/hyperactivity disorder from pervasive developmental disorder not otherwise specified

To discriminate between the various compressing vessels of the facial nerves in patients with hemifacial spasm, pre-operative oblique sagittal gradient-echo MR imaging was performed. Forty-two patients underwent pre-operative MR imaging and microvascular decompression. The MR images were divided according to findings into three groups as follows: Group A, a thick and/or long high-intensity line along the root exit zone (REZ) of the facial nerve; Group B, a thin and/or short high-intensity line along the REZ; and Group C, an unreliable image around the REZ. Fifteen images were classified as Group A, 19 as Group B, and 8 as Group C. In Group A, vertebral artery (VA) compression was confirmed intra-operatively in 12 cases and posterior inferior cerebellar artery (PICA) or anterior inferior cerebellar artery (AICA) compression in 3. In Group B, PICA or AICA compression was confirmed intra-operatively in all cases. In Group C, PICA or AICA compression was confirmed intra-operatively in 7 cases and no compression in one. In all cases of VA compression of the facial nerve, the oblique sagittal gradient-echo images demonstrated a thick and/or long high intensity line along the REZ. Oblique sagittal gradient-echo MR imaging is a useful preoperative planning aid, which can predict the possibility of VA compression prior to microvascular decompression for hemifacial spasm.