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PubMed1996

[Pervasive developmental disorders: neurological perspectives].

The pervasive disorders of development (TPD) or disorders within the spectrum of autism (TEA) are two terms which are often used to describe a well-defined group of behaviour disorders characterized by changes in social interaction and language communication together with repetitive behaviour patterns. This group of disorders has multiple etiologies and the clinical manifestations vary in severity. In this study the incidence of a selected group of neurological changes and neurodiagnostic tests in 421 children with TDP is analyzed. 11% of the children had genetic disorders such as chromosomial disorders, genetic syndromes and family incidence. 18% of the children had motor disorders with hypotonicity being the commonest (85%). 71% of the children were stereotyped. 59% of the children had cogniscitive functions which were appropriate, or nearly so, for their chronological age, 28% of the children had language regression. 13% had epileptic crises. The electroencephalogram and cerebral magnetic resonance were abnormal in 29% and 19% respectively of the children on whom these tests were done.

Brain↗

PubMed2005

Low-birth-weight adolescents: psychiatric symptoms and cerebral MRI abnormalities.

To explore associations between psychiatric symptoms and cerebral magnetic resonance imaging abnormalities in low-birth-weight adolescents, 55 very low-birth-weight ( or=10th centile) were assessed at 14-15 years of age. Outcome measures were Schedule for Affective Disorders and Schizophrenia for School-Age Children, Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Autism Spectrum Screening Questionnaire, and qualitatively assessed cerebral magnetic resonance images. The very low-birth-weight group manifested increased prevalence of psychiatric symptoms and disorders compared with controls (P < 0.001), especially symptoms of attention-deficit/hyperactivity disorder, and high frequency of ventricular dilatation, white matter reduction, thinning of corpus callosum, and gliosis (P < 0.01 vs controls). The Attention-Deficit/Hyperactivity Disorder Rating Scale score was significantly associated with white matter reduction and thinning of corpus callosum in this group. The term small for gestational age group had increased prevalence of psychiatric symptoms compared with control subjects, but not more frequent abnormalities on cerebral magnetic resonance imaging. In conclusion, attention-deficit/hyperactivity disorder symptoms were significantly associated with white matter reduction and thinning of corpus callosum in very low-birth-weight adolescents. No associations were found for other psychiatric symptoms and brain abnormalities in any of the groups.

Adolescent↗

PubMed2005

The orbitofrontal-amygdala circuit and self-regulation of social-emotional behavior in autism.

Individuals with an autistic spectrum disorder are impaired not only in understanding others' mental states, but also in self-regulation of social-emotional behavior. Therefore, a model of the brain in autism must encompass not only those brain systems that subserve social-cognitive and emotional functioning, but also those that subserve the self-regulation of behavior in response to a changing social environment. We present evidence to support the hypothesis that developmental dysfunction of the orbitofrontal-amygdala circuit of the brain is a critical factor in the development of autism and that some of the characteristic deficits of persons with autism in socio-emotional cognition and behavioral self-regulation are related to early dysfunction of different components of this circuit. A secondary hypothesis posits that the degree of intellectual impairment present in individuals with autism is directly related to the integrity of the dorsolateral prefrontal-hippocampal circuit of the brain. Together, these hypotheses have the potential to help explain the neurodevelopmental basis of some of the primary manifestations of autism as well as the heterogeneity of outcomes.

Amygdala↗

PubMed2002

[Clinical diagnosis of autism].

INTRODUCTION: The disorders of the autistic spectrum form a collection of symptoms due to dysfunction of the central nervous system with great variations in the degree of severity. Autism is considered to be a generalized disorder of development (DSM-IV). Autism is not defined as a specific disease, since it does not have a specific aetiology. DEVELOPMENT: There are many syndromes related to autism, but most of these disorders are not selective and show a combination of autistic symptoms together with symptoms of neurological dysfunction. There is no specific aetiology, although in recent years genetics have been shown to be important. The prevalence varies between 1 and 1.2/1,000. Boys are more often affected than girls, in a proportion of 3-4 to 1. Diagnosis is clinical and is based on alterations of social interaction, problems of communication and also a restricted range of activities and interests (DSM-IV). There are anomalies associated with behaviour problems, such as delay in speaking, mental retardation, sensorial defects and motor difficulties. CONCLUSIONS: Over 75% of autistic children have mental retardation, and this proportion is higher in severe cases, especially when the children have attention deficit with hyperactivity. These children have many of the typical signs of autism: stereotyped movements, inappropriate language, obsessive behaviour with little mental flexibility, naivety and little skill in social interaction. In these cases it is difficult to draw the line between mental retardation and autism.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

Autistic spectrum disorders in Möbius sequence: a comprehensive study of 25 individuals.

The prevalence of autistic disorder was analysed in 25 individuals with Möbius sequence, a disorder with brain-stem dysfunction. The sample consisted of 18 males and seven females (20 participants were aged 2 to 22 years, and five were aged 1, 19 and 23 months, and 55 years old). Participants were recruited after a nationwide call and were part of a multidisciplinary study of individuals with Möbius sequence. They were given a meticulous neuropsychiatric examination including standardized autism diagnostic interviews. Ten individuals had an autistic spectrum disorder. Six of these met all diagnostic criteria for autism. In 23 individuals cognitive development could be assessed. Eight of those 23 patients had clear learning disability and six individuals were functioning in the normal but subaverage range. Autistic spectrum disorder and learning disability occurred in more than a third of the examined patients. Considering the hospital-based nature of the sample, these findings may be overestimates. Nevertheless, awareness of this coexistence is important in the diagnosis and habilitation care of children with Möbius sequence. Moreover, the results provide further support for the notion of a subgroup of autistic spectrum disorders being caused by first trimester brain-stem damage.

Adolescent↗

PubMed2004

Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype for autism.

OBJECTIVE: The broader autism phenotype includes relatives of individuals with autism who display social and language deficits that are qualitatively similar to those of autism but less severe. In previous studies of monozygotic twins discordant for autism, more than 75% of the twins without autism displayed the broader phenotype. Differences in neuroanatomy between discordant monozygotic twins might be associated with the narrow and broader behavioral phenotypes. The authors examined the relationship of twin pair differences in clinical phenotype to differences in neuroanatomic phenotype. METHOD: The subjects were 16 monozygotic twin pairs between the ages of 5 and 14 years and 16 matched singleton comparison subjects. Seven twin pairs were clinically concordant and nine twin pairs were clinically discordant for strictly defined autism. After magnetic resonance imaging, a semiautomated procedure was applied to images in which the brain tissue was subdivided into neurofunctional regions and segmented into gray, white, and ventricular compartments. RESULTS: Both the concordant and discordant twin pairs exhibited concordance in cerebral gray and white matter volumes. However, only the clinically concordant pairs exhibited concordance in cerebellar gray and white matter volumes. Within the discordant twin pairs, both the twins with autism and their co-twins exhibited frontal, temporal, and occipital white matter volumes that were lower than those of the comparison subjects. CONCLUSIONS: These findings support the role and the limits of genetic liability in autism. Continuing to clarify the neuroanatomic pathways in autistic spectrum disorders could illuminate the etiology of autism and, ultimately, contribute to treatments.

Adolescent↗

PubMedDate not supplied

Trends in autism.

Leo Kanner described autism in 1943, and Hans Asperger described the syndrome in 1944. The term Pervasive Developmental Disorders (PDD) was first used in the 1980s to describe a class of disorders that include (1) Autistic disorder, (2) Rett disorder or syndrome, (3) Childhood Disintegrative Disorder, (4) Asperger's disorder or syndrome, and (5) Pervasive Developmental Disorder Not Otherwise Specified, or PDDNOS. Autism prevalence studies published before 1985 showed prevalence rates of 4 to 5 per 10,000 children for the broader autism spectrum, and about 2 per 10,000 for the classic autism definition. Since 1985 there have been higher rates of autism reported from several countries. From the UK a prevalence rate of 16.8 per 10,000 children for autistic disorder was reported, and 62.6 per 10,000 for the entire autistic spectrum disorders. Sweden reported a prevalence of 36 per 10,000 for Asperger and 35 per 10,000 for social impairment, or a total prevalence of 71 per 10,000 for suspected and possible cases. From the US, 40 per 10,000 in three to ten year old children for autistic disorder and 67 per 10,000 children for the entire autism spectrum was reported. From the north region in Israel for children born between 1989-93 in the Haifa area, an incidence rate of 10 per 10,000 was found for autism. In recent years concern has been shown about the possible increase in the prevalence of autistic spectrum disorders. Studies have shown an increase, but during these last twenty years diagnostic criteria and definition have also changed. Although many factors are at play, it is evident that there has been an increase.

Autistic Disorder↗

PubMed2006

Sibling risk of pervasive developmental disorder estimated by means of an epidemiologic survey in Nagoya, Japan.

Broad-spectrum autism, referred to as pervasive developmental disorder (PDD), may be associated with genetic factors. We examined 241 siblings in 269 Japanese families with affected children. The sibling incidence of PDD was 10.0% whereas the prevalence of PDD in the general population in the same geographic region was 2.1%. Both of these rates are higher than those reported previously, probably because of the expanded clinical criteria applied. The prevalence in males of the general population was 3.3% and that in females was 0.82%. The sibling incidences were 7.7 and 20.0% for families in which the probands were male and female, respectively. Because the reversed sex ratios correspond to the general rule for a multifactorial threshold model, we suggest that most PDD cases result from the cumulative effects of multiple factors (mostly genetic). The sibling incidences were 0 and 10.9% for families in which the proband had low and normal birth-weight, respectively, suggesting the risk is lower in families with low-birth-weight probands.

Birth Order↗

PubMed2004

Psychiatric symptoms and disorders in adolescents with low birth weight.

OBJECTIVE: To evaluate the prevalence of psychiatric symptoms and disorders associated with low birth weight.Design/study groups: A population based follow up study of 56 very low birthweight (VLBW: birth weight < or = 1500 g), 60 term small for gestational age (SGA: birth weight < 10th centile), and 83 term control (birth weight > or = 10th centile) children at 14 years of age. OUTCOME MEASURES: Schedule for affective disorders and schizophrenia for school aged children, attention deficit/hyperactivity disorder (ADHD) rating scale IV, autism spectrum screening questionnaire, and children's global assessment scale. RESULTS: VLBW adolescents had a higher prevalence of psychiatric symptoms (46%) than controls (13%) (odds ratio (OR) 5.7, 95% confidence interval (CI) 2.5 to 13.0) and more psychiatric disorders (25%) than controls (7%) (OR 4.3, 95%CI 1.5 to 12.0), especially anxiety disorders. Although 25% of the VLBW adolescents had attention problems, ADHD was diagnosed in only 7%. Four VLBW adolescents had symptoms of Asperger's disorder, and the VLBW group had a higher sum score than controls on the autism spectrum screening questionnaire. Although more SGA adolescents had psychiatric symptoms than controls (23% v 13%), the difference was not statistically significant. Results remained essentially the same when adolescents with low estimated intelligence quotient were excluded, and persisted after possible psychosocial confounders had been controlled for. CONCLUSION: VLBW, but not SGA adolescents, have a high risk of developing psychiatric symptoms and disorders by the age of 14, especially attention deficit, anxiety symptoms, and relational problems.

Adolescent↗

PubMed2004

The use and understanding of virtual environments by adolescents with autistic spectrum disorders.

The potential of virtual environments for teaching people with autism has been positively promoted in recent years. The present study aimed to systematically investigate this potential with 12 participants with autistic spectrum disorders (ASDs), each individually matched with comparison participants according to either verbal IQ or performance IQ, as well as gender and chronological age. Participants practised using a desktop 'training' virtual environment, before completing a number of tasks in a virtual café. We examined time spent completing tasks, errors made, basic understanding of the representational quality of virtual environments and the social appropriateness of performance. The use of the environments by the participants with ASDs was on a par with their PIQ-matched counterparts, and the majority of the group seemed to have a basic understanding of the virtual environment as a representation of reality. However, some participants in the ASD group were significantly more likely to be judged as bumping into, or walking between, other people in the virtual scene, compared to their paired matches. This tendency could not be explained by executive dysfunction or a general motor difficulty. This might be a sign that understanding personal space is impaired in autism. Virtual environments might offer a useful tool for social skills training, and this would be a valuable topic for future research.

Adolescent↗

PubMed2003

Language development in autism.

In this short review article, a summary of the behavioural impairments most commonly associated with the spectrum of autism-related disorders is presented, with a slightly amplified account of the defining communication impairment. The patterns of language ability and disability which typically occur in some forms of autism are then outlined, followed by a short section on possible cognitive, or psychological, explanations of these patterns. In particular, the hypothesis that defective socio-affective and socio-cognitive ('theory of mind') causes language impairments, and the hypothesis that temporal processing deficits cause these impairments, are outlined and briefly discussed. An extensive list of references is included, to support and amplify the summary data included in the review.

Autistic Disorder↗

PubMed1998

Autism and other pervasive developmental disorders: exploring the dimensional view.

OBJECTIVE: To examine empirical data on children with autistic disorder (AD), Asperger's disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS) for continuities or distinguishing features between disorder and to see to what extent the Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) diagnostic criteria-reflect observed data. METHOD: Studies were identified in 4 ways. 1)A Medline search from 1976 to the present of articles with the key words autism, pervasive developmental disorder, autistic spectrum disorder, and Asperger; of these articles, those with mesh headings or textwords "cluster," which identified cluster analyses deriving pervasive developmental disorder (PDD) subtypes, were retained 2) The Journal of Autistic and Developmental Disorder from 1990 to the present was hand-searched to identify other empirically derived studies on diagnosis, prevalence, classification, and validity of PDD subtypes. 3) Key review articles were searched for their references. 4) The references of all identified articles were searched. RESULTS: Eight cluster studies were retained for their relevance to diagnostic issues, as were 7 empirically derived studies delineating clinic characteristics of children will AD, Asperger's syndrome, or PDD-NOS. Data suggests that children with PDD may fit into 1 of 2 overlapping groups, including a lower-functioning group with greater developmental compromise, social aloofness, and a greater number of autistic symptoms and a higher-functioning group with higher IQ, fewer autistic symptoms, and more prosocial behavior. The PDD subtype resemble each other and can be seen as existing o a continuum, differing only by degree of impairment. CONCLUSION: Children exhibiting the triad of autistic impairments can be seen as suffering from disorders on a PDD continuum. While the DSM-IV does identify a lower-functioning autistic group (AD), the higher-functioning group is less well served. Asperger's disorder as defined in the DSM-IV is not clearly distinguishable from AD and PDD-NOS, and the PDD-NOS subcategory is not operationalized. Further research is required to elaborate criteria for the higher-functioning PDD group, and measures related to etiology, outcome, and treatment response may help determine which diagnostic criteria can meaningfully separate one disorder from another.

Autistic Disorder↗

PubMed2002

Autism, an extreme challenge to integrative medicine. Part 2: medical management.

Autism and allied autistic spectrum disorders (ASD) present myriad behavioral, clinical, and biochemical abnormalities. Parental participation, advanced testing protocols, and eclectic treatment strategies have driven progress toward cure. Behavioral modification and structured education are beneficial but insufficient. Dietary restrictions, including removal of milk and other casein dairy products, wheat and other gluten sources, sugar, chocolate, preservatives, and food coloring are beneficial and prerequisite to benefit from other interventions. Individualized IgG or IgE testing can identify other troublesome foods but not non-immune mediated food sensitivities. Gastrointestinal improvement rests on controlling Candida and other parasites, and using probiotic bacteria and nutrients to correct dysbiosis and decrease gut permeability. Detoxification of mercury and other heavy metals by DMSA/DMPS chelation can have marked benefit. Documented sulfoxidation-sulfation inadequacies call for sulfur-sulfhydryl repletion and other liver p450 support. Many nutrient supplements are beneficial and well tolerated, including dimethylglycine (DMG) and a combination of pyridoxine (vitamin B6) and magnesium, both of which benefit roughly half of ASD cases. Vitamins A, B3, C, and folic acid; the minerals calcium and zinc; cod liver oil; and digestive enzymes, all offer benefit. Secretin, a triggering factor for digestion, is presently under investigation. Immune therapies (pentoxifyllin, intravenous immunoglobulin, transfer factor, and colostrum) benefit selected cases. Long-chain omega-3 fatty acids offer great promise. Current pharmaceuticals fail to benefit the primary symptoms and can have marked adverse effects. Individualized, in-depth clinical and laboratory assessments and integrative parent-physician-scientist cooperation are the keys to successful ASD management.

Amino Acids↗

PubMed2002

Autism, an extreme challenge to integrative medicine. Part: 1: The knowledge base.

Autism, archetype of the autistic spectrum disorders (ASD), is a neurodevelopmental disorder characterized by socially aloof behavior and impairment of language and social interaction. Its prevalence has surged in recent years. Advanced functional brain imaging has confirmed pervasive neurologic involvement. Parent involvement in autism management has accelerated understanding and treatment. Often accompanied by epilepsy, cognitive deficits, or other neurologic impairment, autism manifests in the first three years of life and persists into adulthood. Its etiopathology is poorly defined but likely multifactorial with heritability playing a major role. Prenatal toxic exposures (teratogens) are consistent with autism spectrum symptomatology. Frequent vaccinations with live virus and toxic mercurial content (thimerosal) are a plausible etiologic factor. Autistic children frequently have abnormalities of sulfoxidation and sulfation that compromise liver detoxification, which may contribute to the high body burden of xenobiotics frequently found. Frequent copper-zinc imbalance implies metallothionein impairment that could compound the negative impact of sulfur metabolism impairments on detoxification and on intestinal lining integrity. Intestinal hyperpermeability manifests in autistic children as dysbiosis, food intolerances, and exorphin (opioid) intoxication, most frequently from casein and gluten. Immune system abnormalities encompass derangement of antibody production, skewing of T cell subsets, aberrant cytokine profiles, and other impairments consistent with chronic inflammation and autoimmunity. Coagulation abnormalities have been reported. Part 2 of this review will attempt to consolidate progress in integrative management of autism, aimed at improving independence and lifespan for people with the disorder.

Autistic Disorder↗

PubMed1988

Autistic spectrum disorders: clinical presentation in preschool children.

It is well recognized that children with "autistic features" constitute a very heterogeneous population. There is a growing consensus that the core symptoms seen in autism include deficits in: (1) social/affective/behavioral functions, (2) developmental language disorders with concomitant deficits in interpersonal communication, and (3) play/preferred activities/preoccupations which have a repetitive or stereotypic quality. The definition of the boundaries of "autism" as opposed to other related pervasive developmental disorders is widely debated among clinicians and research investigators alike. In the present paper, it is argued that autism is a cover term for a spectrum disorder with similarities and differences in the clinical presentation of preschool children. A model for subtyping the autistic spectrum disorders is suggested.

Ammonia↗

PubMed2001

Understanding and caring for the child with Asperger syndrome.

Nurses in a variety of settings encounter children with the unfamiliar diagnosis of Asperger syndrome (AS). This disorder, which falls clinically along the autism spectrum, is receiving increasing attention because of its inclusion in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as one of the pervasive developmental disorders. The characteristic features of AS include deficits in social skills, atypical understanding of and use of pragmatic language, behavior problems, and a restricted set of interests. Cognitive abilities vary, and some children with AS have high intelligence. In addition, many children with AS have other conditions, such as attention deficit hyperactivity disorder, Tourette's syndrome, obsessive-compulsive disorder, and depression. The disorder can result in significant functional difficulties in the home, school, and community contexts. A case study highlights the features of AS, and a related individualized school health care plan demonstrates the school nurse's role in family and staff education, monitoring for comorbidities, behavioral management, medication management, support to family members, and referral.

Asperger Syndrome↗

PubMedDate not supplied

Childhood-onset schizophrenia: timely neurobiological research.

OBJECTIVE: To review timely research on childhood-onset schizophrenia in view of advances in biological research on, and neurodevelopmental theories of, the later-onset disorder. METHOD: Research issues are outlined including further clarification of ICD- and DSM-defined childhood schizophrenia, and differentiation from autism "spectrum" and other subtle, chronic developmental disorders. Key neurobiological advances are reviewed for which child studies are relevant and feasible. CONCLUSION: It is anticipated that narrowly defined childhood-onset schizophrenics will constitute a predominantly male population. A high rate of family illness or chromosomal and/or brain developmental abnormalities, which will be instructive regarding the pathophysiology of later-onset schizophrenia, is expected.

Age of Onset↗

PubMed2002

Genetic and immunologic considerations in autism.

According to recent epidemiological surveys, autistic spectrum disorders have become recognized as common childhood psychopathologies. These life-lasting conditions demonstrate a strong genetic determinant consistent with a polygenic mode of inheritance for which several autism susceptibility regions have been identified. Parallel evidence of immune abnormalities in autistic patients argues for an implication of the immune system in pathogenesis. This review summarizes advances in the molecular genetics of autism, as well as recently emerging concerns addressing the disease incidence and triggering factors. The neurochemical and immunologic findings are analyzed in the context of a neuroimmune hypothesis for autism. Studies of disorders with established neuroimmune nature indicate multiple pathways of the pathogenesis; herein, we discuss evidence of similar phenomena in autism.

Autistic Disorder↗