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PubMed2006

Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome.

Loss-of-function mutations or abnormal expression of the X-linked gene encoding methyl CpG binding protein 2 (MeCP2) cause a spectrum of postnatal neurodevelopmental disorders including Rett syndrome (RTT), nonsyndromic mental retardation, learning disability, and autism. Mice expressing a truncated allele of Mecp2 (Mecp2(308)) reproduce the motor and social behavior abnormalities of RTT; however, it is not known whether learning deficits are present in these animals. We investigated learning and memory, neuronal morphology, and synaptic function in Mecp2(308) mice. Hippocampus-dependent spatial memory, contextual fear memory, and social memory were significantly impaired in Mecp2(308) mutant males (Mecp2(308/Y)). The morphology of dendritic arborizations, the biochemical composition of synaptosomes and postsynaptic densities, and brain-derived neurotrophic factor expression were not altered in these mice. However, reduced postsynaptic density cross-sectional length was identified in asymmetric synapses of area CA1 of the hippocampus. In the hippocampus of symptomatic Mecp2(308/Y) mice, Schaffer-collateral synapses exhibited enhanced basal synaptic transmission and decreased paired-pulse facilitation, suggesting that neurotransmitter release was enhanced. Schaffer-collateral long-term potentiation (LTP) was impaired. LTP was also reduced in the motor and sensory regions of the neocortex. Finally, very early symptomatic Mecp2(308/Y) mice had increased basal synaptic transmission and deficits in the induction of long-term depression. These data demonstrate a requirement for MeCP2 in learning and memory and suggest that functional and ultrastructural synaptic dysfunction is an early event in the pathogenesis of RTT.

Animals↗
PubMed2006

Autistic spectrum disorders 2: diagnosis and management.

As many as six in every 1000 children may be affected by an autistic spectrum disorder. The previous article of this two-part series discussed the distinction between autism, Asperger's syndrome and pervasive developmental disorder, and examined the assessment process. This article looks at potential differential diagnoses that must be considered, as well as conditions associated with autism. Many theories about the causes of autism have been suggested, including the MMR vaccine. Recent research has suggested that there is no link between the vaccine and autism. There is no cure for autism, but intervention and management techniques should be aimed at educating parents and carers about the disorder and behavioural interventions to aid the child's skills development.

Antipsychotic Agents↗
PubMedDate not supplied

Managing autism and Asperger's syndrome in current educational provision.

There is a need to understand the difficulties faced by those with autistic spectrum disorders (ASD) in educational settings if one is to manage and help them manage their learning. This paper explores some of the most pertinent problems that arise. It analyses perceptual, social, conceptual, emotional and memorizing barriers to learning and shows how difficulties in communication are exacerbated by educational language, which gives a poor model for those who have no prior understanding of inter-personal communication. The notion of an 'autism-friendly' environment is examined as is the process of how schools and other learning institutions might be helped to create such an environment. Education as entitlement is distinguished from education as therapy and the implications for inclusion are examined. It is argued that the best teaching arises from an empathetic understanding and a willingness to be flexible, the worst, from rigidity and an expectation that it is the child who must change. There is no single approach that can meet all the needs of those with ASDs, but nor are needs entirely determined by individual behaviour. It is the understanding of ASD that enables the teacher to correctly identify the child's learning needs and begin to meet them.

Adolescent↗
PubMed2006

Is obsessive-compulsive disorder an anxiety disorder?

Obsessive-compulsive disorder (OCD) is classified as an anxiety disorder in the DSM-IV-TR [American Psychiatric Association, 2000. Diagnostic and statistical manual of mental disorders, Fourth ed., rev. Washington, DC: Author]; however, the notion of a spectrum of obsessive-compulsive (OC) related disorders that is comprised of such disparate disorders as OCD, body dysmorphic disorder, certain eating disorders, pathological gambling, and autism, is gaining acceptance. The fact that these disorders share obsessive-compulsive features and evidence similarities in patient characteristics, course, comorbidity, neurobiology, and treatment response raises the question of whether OCD is best conceptualized as an anxiety or an OC spectrum disorder. This article reviews evidence from comorbidity and family studies, as well as biological evidence related to neurocircuitry, neurotransmitter function, and pharmacologic treatment response that bear on this question. The implications of removing OCD from the anxiety disorders category and moving it to an OC spectrum disorders category, as is being proposed for the DSM-V, is discussed.

Anxiety Disorders↗
PubMedDate not supplied

Are we in the midst of an autism epidemic? A review of prevalence data.

Autism is a "developmental disorder of neurobiologic origin that is defined on the basis of developmental and behavioral features." Studies over the past 10-15 years suggest that the prevalence of autism is rising. Media coverage has been extensive and has indicated the presence of an "autism epidemic." The goal of this article is to review relevant epidemiologic studies which address the prevalence of Autistic Spectrum Disorders in the last 30 years.

Age Distribution↗
PubMed2002

Gluten and casein free diets in autism: a study of the effects on food choice and nutrition.

BACKGROUND: There is growing interest in possible dietary involvement in the aetiology and treatment of Autistic Spectrum Disorders (ASD). Research has focused on the physiological and behavioural effects of dietary change but has not examined the effect of exclusion diets on nutritional intake. AIMS: The aim of this study was to examine whether the removal of major dietary staples placed children with autism at risk of nutrient deficiency and compares their food choice with ASD children not following gluten and/or casein free diets. METHODS: A postal questionnaire was sent to parents of children aged 3-16 years, diagnosed with ASD belonging to the National Autistic Society in Leicestershire and southern Derbyshire. Detailed dietary information and a 3-day food diary were collected. The sample size was small: those using gluten/casein free diets (n = 8) and those not following diet (n = 29). RESULTS: Nutrient intakes fell below the Lower Reference Nutrient Intake (LRNI) in 12 children (32%) for zinc, calcium, iron, vitamin A, vitamin B12 and riboflavin in the nondiet group and four children (50%) for zinc and calcium in the diet group. Fruit and vegetable intakes were higher and cereal, bread and potato consumption were lower in those children using gluten and/or casein free diets. CONCLUSION: No significant differences in the energy, protein and micronutrient intakes were found between the two groups of children. A longitudinal prospective study is suggested to examine whether differences in food choice are the result of dietary intervention or the prerequisite for the successful application of diet in this special group of children.

Adolescent↗
PubMed2006

Fetal testosterone and sex differences in typical social development and in autism.

Experiments in animals leave no doubt that androgens, including testosterone, produced by the testes in fetal and/or neonatal life act on the brain to induce sex differences in neural structure and function. In human beings, there is evidence supporting a female superiority in the ability to read nonverbal signals, specific language-related skills, and theory of mind. Even more striking than the sex differences seen in the typical population is the elevated occurrence of social and communicative difficulties in human males. One such condition, autism, occurs four times more frequently in boys than in girls. Recently, a novel theory known as the "extreme male brain" has been proposed. It suggests that the behaviors seen in autism are an exaggeration of typical sex differences and that exposure to high levels of prenatal testosterone might be a risk factor. In this article, we argue that prenatal and neonatal testosterone exposures are strong candidates for having a causal role in sexual dimorphism in human behavior, including social development, and as risk factors for conditions characterized by social impairments, particularly autism spectrum conditions.

Animals↗
PubMed2002

Differentiation between autism and multiple complex developmental disorder in response to psychosocial stress.

Multiple Complex Developmental Disorder (MCDD) represents a distinct group within the autistic spectrum based on symptomatology. Unlike autistic children, part of MCDD children develop schizophrenia in adult life. Despite the differences, patients of both disorders are mainly characterized by abnormal reactions to their social environment. At the biological level, we showed in a previous study that MCDD children have a reduced cortisol response to psychosocial stress. Given the fact that autistic children clinically show more social impairments, it was hypothesized that they may have even further decreased cortisol responses to psychosocial stress than MCDD patients. Therefore, 10 autistic children were compared to 10 MCDD children and 12 healthy control children in their response to a psychosocial stressor, consisting of a public speaking task. In order to test whether any impairments in the biological stress response are specific for psychosocial stress, the autistic children were compared with 11 MCDD children and 15 control children in their response to a physical stressor, consisting of 10 min of bicycle exercise. Heart rate and salivary cortisol levels were used as indicators of response to the stress tests. Autistic children showed a relatively elevated cortisol response to psychosocial stress, in contrast to MCDD children who showed a reduced cortisol response. No differences in heart rate or cortisol responses to the physical stress test were found. The specific difference between autistic and MCDD children in their cortisol response to psychosocial stress indicates that the disturbed reactions to the social environment observed in these disorders may have different biological backgrounds.

Analysis of Variance↗
PubMed2007

Intonation and emotion in autistic spectrum disorders.

The classic picture of an autistic individual includes an impoverished ability to interpret or express emotion. The prosody of spoken language in autistic children is thought to lack emotional content. In this study, the verbal intonation of children with autism was examined and compared to that of children with Asperger Syndrome (AS) and normal controls (ctrl). Utterances elicited by repetition and by spontaneous story completion were analyzed by quantifying phonetic features (pitch, amplitude, and length) and comparing them to subjective ratings of produced emotion (happy, sad or angry). Since the most consistent phonetic correlate of these emotional targets has been demonstrated to be pitch range, speakers with autistic spectrum disorders were expected to have decreased pitch range; however in the repetition task, autistic subjects actually had a larger pitch range than the other groups. Other measures of intonation including amplitude, duration, and location of pitch peak revealed defects that are more complex than predicted. In spontaneous speech, autistic subjects performed more poorly on both phonetic targets and subjective ratings than ctrls, and AS subjects fell between autistics and normals.

Adolescent↗
PubMed2006

Vaccines and the changing epidemiology of autism.

BACKGROUND: The epidemiology of autism has been rather confusing, with very variable published prevalence figures and no clear incidence data. The cause of autism is unclear; vaccines have been incriminated. METHODS: Literature review and interpretation. RESULTS: The recorded prevalence of autism has increased considerably in recent years. This reflects greater recognition, with changes in diagnostic practice associated with more trained diagnosticians; broadening of diagnostic criteria to include a spectrum of disorder; a greater willingness by parents and educationalists to accept the label (in part because of entitlement to services); and better recording systems, among other factors. The cause(s) of autism remains unclear. There is a strong genetic component which, along with prenatally determined neuro-anatomical/biochemical changes, makes any post-natal 'cause' unlikely. CONCLUSIONS: There has (probably) been no real increase in the incidence of autism. There is no scientific evidence that the measles, mumps and rubella (MMR) vaccine or the mercury preservative used in some vaccines plays any part in the aetiology or triggering of autism, even in a subgroup of children with the condition.

Attitude to Health↗
PubMed2002

Defining and quantifying the social phenotype in autism.

OBJECTIVE: Genetic and neurofunctional research in autism has highlighted the need for improved characterization of the core social disorder defining the broad spectrum of syndrome manifestations. METHOD: This article reviews the advantages and limitations of current methods for the refinement and quantification of this highly heterogeneous social phenotype. RESULTS: The study of social visual pursuit by use of eye-tracking technology is offered as a paradigm for novel tools incorporating these requirements and as a research effort that builds on the emerging synergy of different branches of social neuroscience. CONCLUSIONS: Advances in the area will require increased consideration of processes underlying experimental results and a closer approximation of experimental methods to the naturalistic demands inherent in real-life social situations.

Adult↗
PubMed2006

Validity of the social communication questionnaire in assessing risk of autism in preschool children with developmental problems.

This study estimates the sensitivity and specificity of the social communication questionnaire (SCQ) for autistic spectrum disorders in preschool children at high risk for developmental problems referred to a tertiary centre and compares the predictions of the SCQ and the referrer. The SCQ was completed by 81 parents prior to multidisciplinary assessment and compared with the final diagnosis. The sensitivity and specificity were 93% and 58% for children aged 2-6, and 100 and 62% for children aged 3-5 years, with a cut-off score of 11. The SCQ performed better than referrers. Low-specificity means the SCQ is not suitable as a diagnostic tool but will assist clinicians and tertiary services in selecting children with developmental problems who require autism-specific assessment.

Autistic Disorder↗
PubMed2004

Chronic pain in individuals with previously undiagnosed autistic spectrum disorders.

UNLABELLED: The aim of this article is to heighten clinician awareness by describing 2 patients with signs and symptoms of a possible autistic disorder. Autistic spectrum disorders are neurodevelopmental disorders characterized by impairment in reciprocal social interaction skills or communication skills and/or by the presence of stereotyped behavior, interests, and activities. Pain can be the initial presenting symptom for individuals with a previously undiagnosed autistic spectrum disorder. Two case presentations show indicators, such as reported sensory abnormalities, impaired social behaviors, and unusual interests, that should lead the physician to consider a referral for further evaluation. An accurate diagnosis of autism or related disorder can lead to a greater understanding of the nature of the patient's pain, as well as to more appropriate and effective treatment strategies. In addition, such patients might benefit from therapeutic interventions to improve overall functioning and decrease distress and, consequently, to decrease pain and other symptoms. Finally, autism research might inform pain researchers on topics such as neurobiology, development, and treatment of chronic pain disorders. PERSPECTIVE: Pain experts might be underrecognizing signs and symptoms of autistic spectrum disorders (ASDs) in their patients. Clinical evaluation for ASDs should be considered in patients with specific unusual characteristics. Research on the topic of ASDs and pain is encouraged.

Adolescent↗
PubMed2006

Healthcare issues for children on the autism spectrum.

PURPOSE OF REVIEW: We provide a summary of issues relevant to healthcare and health delivery in autism and related disorders, with a focus on work published in the past 5 years. RECENT FINDINGS: Autism has a strong genetic basis as evidenced by the high recurrence rate in families and its associations with Fragile X syndrome and tuberous sclerosis. Early diagnosis of autism is important, given the potential for improvement with intervention. Although its associations have been reported with events such as measles-mumps-rubella immunization, large-scale studies have not supported such links. Controlled drug trials have increased in frequency and drug treatment may be helpful in addressing frequently associated behavioural and emotional difficulties. Alternative treatments are frequently preferred by parents. SUMMARY: Knowledge of autism among healthcare professionals has increased but gaps remain. Physicians and other professionals can facilitate the delivery of healthcare services to individuals with autism. Awareness of empirically validated treatments will facilitate work with individuals with autism and related disorders as well as with their families.

Australia↗
PubMed2001

The effects of inositol treatment in animal models of psychiatric disorders.

Clinical trials indicate that inositol may be effective in the treatment of patients with depression, panic disorder and obsessive compulsive disorder (OCD), but not in the treatment of patients with schizophrenia, Alzheimer's disease, ADHD or autism. This spectrum of clinical action parallels that of serotonin selective reuptake inhibitors (SSRIs), but inositol is a precursor in the phosphatidylinositol cycle, a second messenger system distal to the receptor for 5HT-2. To study its mechanism of therapeutic action there is a need to test inositol's activity in animal models of psychopathology. In rats, chronic inositol was demonstrated to increase activity levels, reduce immobility time in the forced swim test and in the reserpine-induced hypoactivity models of depression, and reduce anxiety-like behaviors in the elevated plus-maze. The reduction in anxiety-like behaviors appears to be related to baseline levels of activity. Inositol treatment was not observed to have any effect on amphetamine-induced hyperactivity, apomorphine-induced stereotypy, or on the performance of memory tasks by monkeys. Clinical controlled trials of inositol in patients with depression, panic disorder, and OCD were small, and positive psychoactive effects in animals clearly strengthen the case for further clinical trials and potential for general therapeutic use in humans.

Affect↗
PubMed2007

State infant/toddler program policies for eligibility and services provision for young children with autism.

The importance of early developmental and behavioral treatment for children with autism is increasingly recognized. Little is known, however, about early intervention policies that may affect service delivery to these children. The current study describes states' policies for providing early intervention services to children with Autistic Spectrum Disorders under the Individuals with Disabilities Education Act Part C and examines how Part C policies are associated with the proportion of school-age children diagnosed with autism served under IDEA. Results indicate few consistencies among states in policies and practices regarding the identification and care of infants and toddlers with autism. The implications of state variation for policy makers are discussed.

Autistic Disorder↗
PubMed2000

Analysis of autism susceptibility gene loci on chromosomes 1p, 4p, 6q, 7q, 13q, 15q, 16p, 17q, 19q and 22q in Finnish multiplex families.

The role of genetic factors in the etiology of the autistic spectrum of disorders has clearly been demonstrated. Ten chromosomal regions, on chromosomes 1p, 4p, 6q, 7q, 13q, 15q, 16p, 17q, 19q and 22q have potentially been linked to autism.1-8 We have analyzed these chromosomal regions in a total of 17 multiplex families with autism originating from the isolated Finnish population by pairwise linkage analysis and sib-pair analysis. Mild evidence for putative contribution was found only with the 1p chromosomal region in the susceptibility to autism. Our data suggest that additional gene loci exist for autism which will be detectable in and even restricted to the isolated Finnish population.

Adolescent↗