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Pervasive developmental disorder and childhood-onset schizophrenia: comorbid disorder or a phenotypic variant of a very early onset illness?

BACKGROUND: Childhood-onset schizophrenia (COS) is a severe form of the adult-onset disorder with a high rate of premorbid developmental abnormalities. Early symptoms of pervasive developmental disorder (PDD) have been reported in five independent studies of COS. In this study, we compared evidence for premorbid PDD as a nonspecific manifestation of impaired neurodevelopment seen in schizophrenia, or as an independent risk factor for COS. METHODS: Diagnosis of past or current autism or PDD was made according to the DSM-IV criteria. COS patients with and without PDD were compared with respect to neuropsychological, clinical, and neurobiological measures. Several candidate genes for autism were examined in the entire COS sample and the subgroup with PDD using the Transmission Disequilibrium Test (TDT) and Quantitative TDT (QTDT). RESULTS: Nineteen (25%) of COS probands had a lifetime diagnosis of PDD: one met criteria for autism, two for Asperger's disorder, and 16 for PDD not otherwise specified. Premorbid social impairment was most common feature for COS-PDD subjects. The PDD group did not differ from the rest of the COS sample with respect to age of onset, IQ, response to medications, and rate of familial schizotypy. Unexpectedly, two siblings of COS-PDD probands met criteria for nuclear autism. There was no difference between PDD and non-PDD groups with respect to initial brain magnetic resonance imaging (MRI) measures. However, rate of gray matter loss was greater for PDD (n = 12) than for the non-PDD (n = 27) subgroup (-19.5 +/- 11.3 mL/year vs. -9.6 +/- 15.3 mL/year; p =.05). None of eight candidate genes for autism were associated with COS or COS-PDD. CONCLUSIONS: Premorbid PDD in COS is more likely to be a nonspecific marker of severe early abnormal neurodevelopment. However, the occurrence of two siblings of COS-PDD probands (17%) with nuclear autism remains to be understood.

Adolescent↗

Diagnosis of autism and other pervasive developmental disorders.

Problems in the diagnosis of autism and other pervasive developmental disorders are reviewed. Modification and application of recent developments in neuroimaging, molecular genetics and population studies are presented. A prioritized list of needed investigations is discussed.

Autistic Disorder↗

Childhood Onset Pervasive Developmental Disorder.

Two male children meeting criteria for Childhood Onset Pervasive Developmental Disorder (COPDD) are described. The current DSM-III category of COPDD may have value in separating these children from others with PDD. The authors suggest that these two children, and other children described in the literature as having dementia infantalis and/or disintegrative psychosis, have a distintegrative disorder resulting in muteness, profound mental retardation and severe autistic symptomatology. The term "pervasive disintegrative disorder" may be appropriate for such children and specific diagnostic criteria are suggested. The disorder appears to be extremely rare, with a prevalence estimate of 0.11 per 10,000.

Age Factors↗

The pervasive developmental disorder spectrum: a case illustration.

Children diagnosed with a pervasive developmental disorder experience difficulties along a spectrum of severity. Impairments in socialization, communication, and the ability to appropriately express and interpret affect in relationships are common features of the disorder. After summarizing salient thinking in the field, the author describes a case emphasizing the individual psychotherapy process in which the patient was involved. Although individual psychotherapy with such patients is currently viewed with skepticism, the one-on-one relationship may be a central feature of such treatment because it can serve as a model for other relationships. The author advocates a multimodal treatment plan appropriately geared to the needs of such patients.

Adolescent↗

Plasticity of nonneuronal brain tissue: roles in developmental disorders.

Neuronal and nonneuronal plasticity are both affected by environmental and experiential factors. Remodeling of existing neurons induced by such factors has been observed throughout the brain, and includes alterations in dendritic field dimensions, synaptogenesis, and synaptic morphology. The brain loci affected by these plastic neuronal changes are dependent on the type of experience and learning. Increased neurogenesis in the hippocampal dentate gyrus is a well-documented response to environmental complexity ("enrichment") and learning. Exposure to challenging experiences and learning opportunities also alters existing glial cells (i.e., astrocytes and oligodendrocytes), and up-regulates gliogenesis, in the cerebral cortex and cerebellum. Such glial plasticity often parallels neuronal remodeling in both time and place, and this enhanced morphological synergism may be important for optimizing the functional interaction between glial cells and neurons. Aberrant structural plasticity of nonneuronal elements is a contributing factor, as is aberrant neuron plasticity, to neurological and developmental disorders such as epilepsy, autism, and mental retardation (i.e., fragile X syndrome). Some of these nonneuronal pathologies include abnormal cerebral and cerebellar white matter and myelin-related proteins in autism; abnormal myelin basic protein in fragile X syndrome (FXS); and abnormal astrocytes in autism, FXS, and epilepsy. A number of recent studies demonstrate the possibility of using environmental and experiential intervention to reduce or ameliorate some of the neuronal and nonneuronal abnormalities, as well as behavioral deficits, present in these neurological and developmental disorders.

Autistic Disorder↗

Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder.

BACKGROUND: Secretin is a peptide hormone that stimulates pancreatic secretion. After recent publicity about a child with autism whose condition markedly improved after a single dose of secretin, thousands of children with autistic disorders may have received secretin injections. METHODS: We conducted a double-blind, placebo-controlled trial of a single intravenous dose of synthetic human secretin in 60 children (age, 3 to 14 years) with autism or pervasive developmental disorder. The children were randomly assigned to treatment with an intravenous infusion of synthetic human secretin (0.4 microg per kilogram of body weight) or saline placebo. We used standardized behavioral measures of the primary and secondary features of autism, including the Autism Behavior Checklist, to assess the degree of impairment at base line and over the course of a four-week period after treatment. RESULTS: Of the 60 children, 4 could not be evaluated - 2 received secretin outside the study, and 2 did not return for follow-up. Thus, 56 children (28 in each group) completed the study. As compared with placebo, secretin treatment was not associated with significant improvements in any of the outcome measures. Among the children in the secretin group, the mean total score on the Autism Behavior Checklist at base line was 59.0 (range of possible values, 0 to 158, with a larger value corresponding to greater impairment), and among those in the placebo group it was 63.2. The mean decreases in scores over the four-week period were 8.9 in the secretin group and 17.8 in the placebo group (mean difference, -8.9; 95 percent confidence interval, -19.4 to 1.6; P=0.11). None of the children had treatment-limiting adverse effects. After they were told the results, 69 percent of the parents of the children in this study said they remained interested in secretin as a treatment for their children. CONCLUSIONS: A single dose of synthetic human secretin is not an effective treatment for autism or pervasive developmental disorder.

Adolescent↗

The emergence of psychopathy: implications for the neuropsychological approach to developmental disorders.

In this paper, I am going to examine the disorder of psychopathy and consider how genetic anomalies could give rise to the relatively specific neuro-cognitive impairments seen in individuals with this disorder. I will argue that genetic anomalies in psychopathy reduce the salience of punishment information (perhaps as a function of noradrenergic disturbance). I will argue that the ability of the amygdala to form the stimulus-punishment associations necessary for successful socialization is disrupted and that because of this, individuals with psychopathy do not learn to avoid actions that will harm others. It is noted that this model follows the neuropsychological approach to the study of developmental disorders, an approach that has been recently criticized. I will argue that these criticisms are less applicable to psychopathy. Indeed, animal work on the development of the neural systems necessary for emotion, does not support a constructivist approach with respect to affect. Importantly, such work indicates that while environmental effects can alter the responsiveness of the basic neural architecture mediating emotion, environmental effects do not construct this architecture. However, caveats to the neuropsychological approach with reference to this disorder are noted.

Amygdala↗

A girl with pervasive developmental disorder and complex chromosome rearrangement involving 8p and 10p.

We report a 4-year-old girl with a de novo, apparently balanced complex chromosome rearrangement. She initially presented for assessment of velopharyngeal insufficiency due to hypernasal speech. She has distinctive facial features (long face, broad nasal bridge, and protuberant ears with simplified helices), bifid uvula, strabismus, and joint laxity. She is developmentally delayed, with language and cognitive skills approximately 2 SD below the mean expected for her age, and meets ADI, ADOS, and DSM-IV criteria for pervasive developmental disorder. She has poor eye contact, atypical communication and social interaction, repetitive behaviours and significant difficulties with processing sensory input. Her karyotype is characterized by the presence of two derivative chromosomes; 46,XX, der(8)(10pter- >10pl2.32::8p12- >8qter), der(l0)(8pter- >8p21.3::10p12.32- >10p11.23::8p21.3- > 8p12::10p11.23- >l0qter). The der(8) is a result of translocation of the segment 10p12.32-pter onto 8p12. The der(l0) has two 8p segments collectively from 8p12-pter in that the segment 8p21.3-pter is translocated onto 10p12.32 and the segment 8p12-p21.3 is inserted at 10p11.23. FISH analysis showed no microdeletion of the major locus at 22q11.2 nor for the minor locus at 10p13p14. This case suggests that aberrations at 8p12, 8p21.3, 10p11.23 and/or 10p12.32 may result in pervasive developmental disorder, associated with mild cognitive delay and specific facial anomalies.

Child Development Disorders, Pervasive↗

[The role of nurses in early rehabilitation of children with developmental disorders].

The role of nurse in early rehabilitation of children with developmental disorders in our country is still not clear and little investigated. The main purpose of the study was to analyze the needs of nursing at the department of Early Rehabilitation, describe appropriate activity spheres for the nurses, and prepare methodical recommendations for the nurse's work with developmentally disabled children. The study was carried out at the in-patient department of Early Rehabilitation, Child Development Center, Vilnius University Hospital. Eighty six mothers of developmentally disabled children were interviewed and filled the questionnaire developed by the authors. Aspects of mothers' views, opinions, suggestions and needs were investigated. The data revealed an interesting overview of the current situation in the field from the patient's perspective. The need for the adequate nurse and care was obvious. The role of the nurses is underestimated and functions could be broader expanded regarding the specific needs of the disabled children and their families. Organizational and practical recommendations are provided.

Child↗

Handedness and cognitive functions in pervasive developmental disorders.

This paper is concerned with what abnormal handedness in Pervasive Developmental Disorders (PDD) reveals about the presence, lateralization, and severity of cerebral dysfunction in this population. From previous work, it was predicted that left-handedness would be elevated in the sample and that mixed-handedness subjects should be more impaired than those with established hand dominance. A battery of cognitive and motor tests were administered to a group of PDD children with autistic symptoms, and performance was compared for the left-handed, right-handed, and mixed-preference children. It was found that left-handers tended to do better than right-handers on all cognitive measures, while the mixed-preference children tended to be the lowest on all cognitive measures. No differences were found on motor measures. An extension of the Satz (1972) model, assuming early brain damage, was developed to explain the superiority of the left-handed children; an alternative explanation assuming anomalous lateralization patterns in the natural left-handers was also suggested.

Adolescent↗

School refusal in pervasive developmental disorders.

Of 135 autistic and/or mentally retarded youngsters, 30 with pervasive developmental disorders and 2 with nonautistic mental retardation showed school refusal according to its modified definition. School refusal was significantly more frequent in other PDDs than in nonautistic mental retardation. The intellectual level was significantly higher in PDD children with school refusal than those without it. A certain level of mental development and obsessive tendency appear necessary for PDD children to develop school refusal. In order to treat school refusal in PDD, it is important to make school a pleasant place to go and to encourage the child to attend.

Absenteeism↗

Prevalence of pervasive developmental disorder in a sample of psychiatrically hospitalized children and adolescents.

Pervasive developmental disorder (PDD) is underrecognized because of lack of awareness of the wide range of severity and differing manifestations of the disorder. A survey of psychiatrically hospitalized children and adolescents was conducted. 3.2% of the sample of boys was found to have PDD. Underappreciation of the presence of PDD characterized the patients. Family members experienced a wide array of psychiatric symptoms and showed evidence for the presence of familial Tourette syndrome.

Adolescent↗

Direct health care costs for children with pervasive developmental disorders: 1996-2002.

We compared direct costs of treatment of Pervasive Developmental Disorder (PDD), asthma, and diabetes in children aged 3-17 years. A retrospective, claims-based study was conducted using the California Medicaid (Medi-Cal) database (1996-2002). Seven hundred and thirty-one children with PDD were identified and matched for sex with an equal number of randomly selected children with asthma and diabetes. Mean total health care costs for PDD were two- to threefold higher than for asthma and diabetes post-diagnosis ($4,815 vs. $1,469 vs. $2,404, respectively, P < 0.0001). Children with PDD incur significantly greater health care costs when compared with children with other chronic pediatric diseases.

Adolescent↗

Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a novel developmental disorder in Gypsies maps to 18qter.

We have identified a novel developmental disorder with complex phenotypic characteristics involving primarily the nervous system, which appears to be common in a specific Gypsy group in Bulgaria. We propose to refer to the syndrome as congenital cataracts facial dysmorphism neuropathy (CCFDN). We have assigned the disease locus to the telomeric region of chromosome 18q. Linkage disequilibrium and highly conserved haplotypes suggest genetic homogeneity and founder effect. CCFDN co-localises with an EST which shows high homology to a conserved Drosophila gene involved in the regulation of nervous system development in vertebrates.

Adolescent↗

[Behavioral problems in children with specific and pervasive developmental disorders, evaluated with the psychopathology assessment scale (AMDP)].

Children with specific developmental disorders of speech and language have an increased rate of psychiatric disorder compared to children developing normally. Children with early infantile autism show psychopathological symptoms in addition to those that are required for the diagnosis. These are often important in daily dealings with the children. As part of a larger study 4 groups of school age children (21 with normal development, 18 with an expressive language disorder, 21 with a receptive language disorder and 11 children with early infantile autism) were rated according to the psychopathological documentation for children (AMDP) within the assessment situation and according to reports of the behaviour outside. Several items were added to include symptoms that are not rated in the present documentation. Significant differences in the means were found between the group of children with autism and the control group. The children with language disorder showed a high variance which was interpreted as a sign for a heterogeneous group. Several of the added items improve the documentation of psychopathological findings in young school children.

Age Factors↗

A comparison of breastfeeding rates among children with pervasive developmental disorder, and controls.

The breastfeeding rates for 50 children with pervasive developmental disorder (PDD) from North Dakota's roster of PDD patients were compared with the national average and with the rates for a control group matched for age, sex, and IQ. In addition, the breastfeeding rates for the normal siblings of the PDD and control groups were compared with the national average to help determine whether the lower breastfeeding rate among PDD patients was a function of parenting practices. The breastfeeding rates for the PDD and control groups were not significantly different from each other, but both were significantly lower than the national average. The breastfeeding rate for the normal siblings of PDD children was almost identical to the national average, but the rate for the siblings of the matched control group was significantly lower than the national average. These results are discussed in terms of hypotheses regarding the early parent-child interactions and characteristics in the families of PDD children.

Autistic Disorder↗

[Classification systems for the clinical approach to pervasive developmental disorders].

This paper compares four systems for the classification of pervasive developmental disorders: DSM-III-R, ICD-10, the French classification of mental disorders in children and adolescents and Manzano and Palacio-Espasa's operational classification. Five children were examined according to a protocol which included clinical and instrumental examination, the BSE scale, a development scale and a psychodynamic observation recorded by video camera. A detailed discussion of the diagnosis of one of the cases is reported as an example, while a synthetic description is given of the other four. The comparison highlights the characteristics of the four systems considered. The differing theoretical premises which inspire them mean that it is important to use all four in the clinical investigation of each case: DSM-III-R and ICD-10 can be used for the initial screening, whilst the other two can be used to classify more specifically all the forms of infantile psychosis.

Autistic Disorder↗